S. Hrg. 114–661 

RIGHT TO TRY 

HEARING 

BEFORE THE

COMMITTEE ON 

HOMELAND SECURITY AND 

GOVERNMENTAL AFFAIRS 

UNITED STATES SENATE 

ONE HUNDRED FOURTEENTH CONGRESS 

SECOND SESSION 

CONNECTING PATIENTS TO NEW AND POTENTIAL LIFE SAVING 

TREATMENTS, FEBRUARY 25, 2016 

EXPLORING A RIGHT TO TRY FOR TERMINALLY ILL PATIENTS, 

SEPTEMBER 22, 2016 

Available via the World Wide Web: http://www.fdsys.gov/ 

Printed for the use of the 

Committee on Homeland Security and Governmental Affairs 

( 
RIGHT TO TRY—2016 
U.S. GOVERNMENT PUBLISHING OFFICE

WASHINGTON : 

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Internet: bookstore.gpo.gov Phone: toll free (866) 512–1800; DC area (202) 512–1800

Fax: (202) 512–2104 Mail: Stop IDCC, Washington, DC 20402–0001

22–718 PDF 2017

S. Hrg. 114–661 

RIGHT TO TRY 

HEARING 

BEFORE THE

COMMITTEE ON 

HOMELAND SECURITY AND 

GOVERNMENTAL AFFAIRS 

UNITED STATES SENATE 

ONE HUNDRED FOURTEENTH CONGRESS 

SECOND SESSION 

CONNECTING PATIENTS TO NEW AND POTENTIAL LIFE SAVING 

TREATMENTS, FEBRUARY 25, 2016 

EXPLORING A RIGHT TO TRY FOR TERMINALLY ILL PATIENTS, 

SEPTEMBER 22, 2016 

Available via the World Wide Web: http://www.fdsys.gov/ 

Printed for the use of the 

Committee on Homeland Security and Governmental Affairs 

( 
(II) 

COMMITTEE ON HOMELAND SECURITY AND GOVERNMENTAL AFFAIRS 

RON JOHNSON, Wisconsin Chairman 

JOHN MCCAIN, Arizona 

ROB PORTMAN, Ohio 

RAND PAUL, Kentucky 

JAMES LANKFORD, Oklahoma 

MICHAEL B. ENZI, Wyoming 

KELLY AYOTTE, New Hampshire 

JONI ERNST, Iowa 

BEN SASSE, Nebraska 

THOMAS R. CARPER, Delaware 

CLAIRE MCCASKILL, Missouri 

JON TESTER, Montana 

TAMMY BALDWIN, Wisconsin 

HEIDI HEITKAMP, North Dakota 

CORY A. BOOKER, New Jersey 

GARY C. PETERS, Michigan 

KEITH B. ASHDOWN, Staff Director 

CHRISTOPHER R. HIXON, Staff Director 

SATYA P. THALLAM, Chief Economist 

DANIEL P. LIPS, Policy Director 

JOSHUA P. MCLEOD, Professional Staff Member 

GABRIELLE A. BATKIN, Minority Staff Director 

JOHN P. KILVINGTON, Minority Deputy Staff Director 

KATHERINE C. SYBENGA, Minority Chief Counsel for Governmental Affairs 

BRIAN F. PAPP, JR., Minority Professional Staff Member 

LYNN SHA, Senior Health Policy Advisor, Office of Senator Carper 

LAURA W. KILBRIDE, Chief Clerk 

BENJAMIN C. GRAZDA, Hearing Clerk 
(III) 

C O N T E N T S 

Page 

THURSDAY, FEBRUARY 25, 2016 

Opening statements: 

Senator Johnson ............................................................................................... 1 

Senator Carper ................................................................................................. 3 

Senator Ernst .................................................................................................... 22 

Senator Ayotte .................................................................................................. 28 

Prepared statements: 

Senator Johnson ............................................................................................... 35 

Senator Carper ................................................................................................. 37 

WITNESSES 

Darcy Olsen, President and Chief Executive Officer, Goldwater Institute ......... 4 

Laura McLinn, Indianapolis, Indiana (accompanied by Jordan McLinn) ........... 6 

Diego Morris, Phoenix, Arizona .............................................................................. 8 

Joseph V. Gulfo, M.D., Executive Director, Rothman Institute of Innovation 

and Entrepreneurship, Farleigh Dickinson University .................................... 10 

Nancy Goodman, Executive Director, Kids v Cancer ........................................... 12 

ALPHABETICAL LIST OF WITNESSES

Goodman, Nancy: 

Testimony .......................................................................................................... 12 

Prepared statement .......................................................................................... 187 

Gulfo, Joseph V., M.D..: 

Testimony .......................................................................................................... 10 

Prepared statement with attachments ........................................................... 94 

McLinn, Laura: 

Testimony .......................................................................................................... 6 

Prepared statement .......................................................................................... 88 

Morris, Diego: 

Testimony .......................................................................................................... 8 

Prepared statement .......................................................................................... 91 

Olsen, Darcy: 

Testimony .......................................................................................................... 4 

Prepared statement with attachment ............................................................. 39 

APPENDIX 

McLinn Fact Sheet .................................................................................................. 191 

Letters referenced by Senator Johnson ................................................................. 193 

Patient Access to Investigational Therapies (FDA Factsheet) ............................. 209 

Statements submitted for the Record from: 

Abigail Alliance for Better Access to Developmental Drugs ......................... 210 

Americans for Safe Access ............................................................................... 214 

Responses to post-hearing questions for the Record from: 

Ms. Olsen .......................................................................................................... 235 

THURSDAY, SEPTEMBER 22, 2016 

Opening statements: 

Senator Johnson ............................................................................................... 237 

Senator Carper ................................................................................................. 239 

Senator Paul ..................................................................................................... 257 
Page

IV 

Opening statements—Continued 

Senator Lankford .............................................................................................. 272 

Prepared statements: 

Senator Johnson ............................................................................................... 281 

Senator Carper ................................................................................................. 282 

WITNESSES 

Matthew Bellina, Lieutenant Commander, U.S. Navy (Retired) ......................... 241 

Hon. Ian C. Calderon, Majority Leader, State Assembly, State of California .... 243 

Hon. Jim Neely, D.O., Member, House of Representatives, State of Missouri ... 246 

Richard Garr, Former President and Chief Executive Officer, Neuralstem, 

Inc. ......................................................................................................................... 247 

Andrew McFadyen, Executive Director, The Isaac Foundation ........................... 249 

Eric and Frank Mongiello ....................................................................................... 251 

Peter Lurie, M.D., M.P.H., Associate Commissioner for Public Health Strategy 

and Analysis, Food and Drug Administration, U.S. Department of Health 

and Human Services ............................................................................................ 266 

ALPHABETICAL LIST OF WITNESSES

Bellina, Matthew: 

Testimony .......................................................................................................... 241 

Prepared statement .......................................................................................... 284 

Calderon, Hon. Ian C.: 

Testimony .......................................................................................................... 243 

Prepared statement .......................................................................................... 286 

Garr, Richard: 

Testimony .......................................................................................................... 247 

Prepared statement .......................................................................................... 296 

Lurie, Peter, M.D., M.P.H.: 

Testimony .......................................................................................................... 266 

Prepared statement .......................................................................................... 307 

McFadyen, Andrew: 

Testimony .......................................................................................................... 249 

Prepared statement .......................................................................................... 299 

Mongiello, Eric and Frank: 

Testimony .......................................................................................................... 251 

Neely, Hon. Jim: 

Testimony .......................................................................................................... 246 

Prepared statement .......................................................................................... 292 

APPENDIX 

Chart submitted by Senator Johnson .................................................................... 313 

Individual Patient Expanded Access Investigational New Drug Application 

(IND) (FDA Form) ................................................................................................ 314 

Patient Access to Investigational Therapies (FDA Factsheet) ............................. 315 

Responses to post-hearing questions for the Record from: 

Mr. Calderon ..................................................................................................... 317 

Mr. Neely ........................................................................................................... 318 

Mr. Garr ............................................................................................................ 319 

Mr. Lurie ........................................................................................................... 320 
(1) 

CONNECTING PATIENTS TO NEW AND 

POTENTIAL LIFE-SAVING TREATMENTS 

THURSDAY, FEBRUARY 25, 2016 

U.S. SENATE, COMMITTEE ON HOMELAND SECURITY

AND GOVERNMENTAL AFFAIRS, Washington, DC. 

The Committee met, pursuant to notice, at 10:02 a.m., in room 

SD–342, Dirksen Senate Office Building, Hon. Ron Johnson, Chairman of the Committee, presiding. 

Present: Senators Johnson, Lankford, Ayotte, Ernst, Sasse, Carper, McCaskill, Heitkamp, and Peters. 

OPENING STATEMENT OF CHAIRMAN JOHNSON 

Chairman JOHNSON. Good morning. This hearing will come to 

order. 

I just want to thank all of the witnesses and everybody in the 

audience for attending what I think is a really important hearing. 

The title of the hearing is: ‘‘Connecting Patients to New and Potential Life-Saving Treatments.’’ We are going to be talking to Darcy 

Olsen, who has certainly been at the forefront of trying to pass— 

and successfully passing—legislation called ‘‘Right to Try’’ in States 

and trying to take a look at that on a Federal basis. 

From a personal standpoint, I do not expect anybody to understand my story, but our first child, our daughter, Carey, was born 

with a pretty serious congenital heart defect. And, her first day of 

life, modern medicine saved her life with a procedure. 

Eight months later, when her heart was the size of a small plum, 

they rebaffled the upper chamber of her heart. And so her heart 

operates backward today, but she is 32 years old and she has lived 

a perfectly normal life. 

When we were going through that, the term ‘‘medical practice’’ 

always kept running through my mind, because I never thought of 

it in terms of what it really meant—medical practice—that there 

is nothing certain. There is no therapy, there is no procedure, and 

there is no drug that performs exactly the same with every person. 

Every person is different. And so, the advancement of medicine 

really does rely on the expertise of individual doctors working with 

patients, patients that should have the freedom to be able to try 

things, particularly, when we know the end result. 

So this hearing is about allowing patients that freedom—and it 

is such common sense. Just let people try. 

But then, when you start getting past the obvious conclusion— 

that, well, people should have the right to make these decisions 
2 

1The prepared statement of Senator Johnson appears in the Appendix on page 35. 

themselves—you start getting into the problems, the legitimate 

problems and concerns of whether it is the responsibility of the 

Food and Drug Administration (FDA) or the companies that are 

producing the drugs or the procedures—and there are legitimate 

concerns. It gets complex pretty fast. 

But, at the heart of this issue, it really is about people. And I 

would ask that my written opening statement be entered in the 

record, without objection.1

We also have a binder of 200 letters submitted to this Committee 

in favor of us holding this hearing. I normally do not spend a whole 

lot of time on an opening statement, but I just wanted to read at 

least one letter. This comes from Tim Wendler of Waukesha, Wisconsin. He is the husband of the late Trickett Wendler, who I did 

meet back in 2014. She had amyotrophic lateral sclerosis (ALS). 

And Tim writes: 

‘‘My wife, Trickett Wendler, passed on March 18, 2015, after a 

2-year battle with amyotrophic lateral sclerosis (ALS). When she 

was first diagnosed, we scoured the country to find the best doctors, medicine, treatments, etc. The only treatment drug prescribed 

for my wife was the exact same drug that was prescribed to her 

father over 20 years ago. Literally no progress. I will tell you that 

once we were out of options, our desire to transform the possibilities became the singular focus of our life. I have three small children with the hereditary gene that predisposes them to this intolerant disease. That is why it is infinitely important to provide patients with alternatives where none exist. The ‘Right to Try’ provides something that doctors, drug manufacturers, legislators, 

etc.—cannot provide: hope.’’ 

Sadly, my wife did not have this option, but I write to you today 

to implore to you the importance of providing hope where none exists. I pray every day that progress is made to find a cure and that 

my children are not given the same drug that their mother and 

grandfather were given. But if none is made, I pray that my children will have the ‘Right to Try.’ 

Now, I read that one because, when I did meet Trickett, this was, 

quite honestly, shortly after I met you, Darcy, and was made aware 

of what you were trying to do with ‘‘Right to Try.’’ And without 

prompting, without being asked, I made the statement, ‘‘I know 

about this initiative, I am fully supportive of ‘Right to Try,’ ’’ and 

tears started streaming down her cheeks. 

That has an effect. And the purpose of this hearing now is to put 

a face—a human face—so that we in Congress can make some intelligent decisions here—so that we can try and break through the 

legitimate concerns of whether it is the FDA or the drug manufacturers and give people, give patients the freedom and the access so 

that they have hope. And that is really what this hearing is all 

about. 

I again thank the witnesses for very thoughtful testimony. It will 

be powerful testimony. And I just want to thank my colleagues for 

coming because I think that this is one of the most important hearings that we will hold. 

With that, Senator Carper. 
3 

OPENING STATEMENT OF SENATOR CARPER 

Senator CARPER. Thank you. Thank you so much, Mr. Chairman. 

Thank you for bringing this together this morning. I appreciate 

your willingness to open a conversation about an issue that is important to all of us, especially to Americans that are seeking access 

to potentially life-saving treatment and new medical innovations 

for themselves or members of their families. 

I want to thank young Jordan for bringing his Mom today to be 

one of our witnesses, so that she can tell your story. I want to 

thank Ms. Olsen, Mr. Morris, Dr. Gulfo, and Ms. Goodman for 

being with us, especially for those of you who are going to share 

your own stories with us today. 

One of the things that the Chairman does as we start a hearing, 

before the witnesses speak, he swears in the witnesses—and this 

is going to be interesting to see how young Jordan, age five, handles that. It will be one for the books. Jordan, we are glad that you 

are here. All I can say is that when my boys were 5 years old, there 

was no way in the world that I would have put them at this table. 

I know—excuse me—six. My sheet here says five. But there is no 

way that I would have done that. [Laughter.] 

They would have wrecked the hearing. But you seem to be very 

well behaved—better than some of us. 

Today, we are going to hear from patients, we are going to hear 

from their loved ones, and we are going to hear from others about 

potential opportunities, hopefully, to improve access to medical 

breakthroughs and to life-saving medical treatments. These folks 

and their families have faced some of the most difficult and challenging circumstances and decisions that just about anybody could 

face, and they deserve our compassion and they deserve our understanding. And they certainly are going to get our attention, today. 

Speaking as a dad, as a husband, as a brother, and as a son, it 

is important that we learn from our witnesses’ experiences so that 

we in Congress can maybe work better together with the Executive 

Branch, with patient groups, with industry, and with other stakeholders to ensure that all Americans can gain access to safe and 

effective life-saving treatments as quickly as possible. 

Simply put, the development of new medicines is, as we know, 

a long, complex, and risky process—an expensive process. For individuals with life-threatening conditions and for their loved ones, 

safe and effective treatments cannot come quickly enough. 

As we will hear from some of our witnesses today, the path for 

patients and their physicians to access innovative, new treatments 

may not always be clear. Reforms may be needed to make sure that 

patients, their families, and their doctors have the information that 

they need to explore new treatment options. 

The U.S. Food and Drug Administration, which is charged with 

ensuring that the drugs available to American consumers are safe 

and effective, has given an extraordinary level of attention to the 

requests of patients with life-threatening conditions. In fact, I am 

told that they have approved more than 99 percent of requests for 

emergency treatments. 

Despite these high approval rates, I understand that the FDA believes that more can be done and that they are continuing, at the 
4 

1The letters referenced by Senator Johnson appears in the Appendix on page 193. 

2The prepared statement of Ms. Olsen appears in the Appendix on page 39. 

FDA, to work to improve patient access to these experimental medical treatments. 

I hope that we can help with some of those efforts and continue 

to work closely with the patients, with health care providers, with 

the pharmaceutical industry, and with the FDA to ensure that all 

patients and their families can access safe and reliable treatments 

as quickly as possible. 

Again, we are delighted that you are all here, and it is just a real 

special treat to see young Jordan at 6 years old—Jordan, when is 

your birthday? 

Chairman JOHNSON. May 15. 

Senator CARPER. May 15. All right. Well, good, a day to remember. Thank you very much. Welcome, everybody. 

Chairman JOHNSON. So almost seven—and, by the way, he is a 

great writer and a good speller—a lot further progressed than I 

was in kindergarten, trust me. 

I do want to explicitly ask consent to enter those letters for the 

record1 and I also want to let all of the Members know that we will 

distribute those to your offices as well. 

As Senator Carper said, it is the tradition of this Committee to 

swear in witnesses, so if you will all rise and raise your right hand. 

Do you swear the testimony you will give before this Committee 

will be the truth, the whole truth, and nothing but the truth, so 

help you, God? 

Ms. OLSEN. I do. 

Ms. MCLINN. I do. 

Master McLinn. I do. 

Mr. MORRIS. I do. 

Ms. GOODMAN. I do. 

Dr. GULFO. I do. 

Chairman JOHNSON. Thank you. Please be seated. 

Our first witness is Darcy Olsen. Ms. Olsen is the president and 

Chief Executive Officer (CEO) of the Goldwater Institute in Phoenix, Arizona and the author of the book ‘‘The Right to Try.’’ She 

is a graduate of Georgetown University and New York University. 

She is also a recipient of numerous awards for her work in public 

policy, including a 2014 Bradley Prize. Ms. Olsen. 

TESTIMONY OF DARCY OLSEN,2 PRESIDENT AND CHIEF 

EXECUTIVE OFFICER, GOLDWATER INSTITUTE 

Ms. OLSEN. Thank you, Chairman Johnson, Ranking Member 

Carper, and other Members of the Committee. Thank you for being 

here today. 

As I was preparing my testimony for you on Monday, I received 

a call from an old friend of mine, who called to tell me that she 

had recently received an ALS diagnosis—or what a lot of people 

know as Lou Gehrig’s disease. And, although it has only been a few 

weeks since the diagnosis, her deterioration has been so rapid that 

they have already called in hospice to plan for those final days. 

And, as her physicians explained to her, ALS is 100 percent fatal, 

and there really are no treatments. And this goes, of course, Chair-
5 

man Johnson, to what you were saying. The same medicines that 

they were using 20 years ago are what they are using today. 

But what Hazel’s doctors really mean is that, in their toolbox of 

approved medicines, there is nothing left, because the truth is that 

right now, pending before the FDA, there are a dozen treatments 

to treat ALS and there is possibly even a cure. And in my book, 

‘‘The Right to Try,’’ I tell the story of a man named Ted Harada— 

and we call Ted ‘‘Lazarus’’ because he is the first known survivor 

of Lou Gehrig’s. He was very fortunate to get into a clinical trial 

where he received a treatment that reversed his ALS symptoms. 

Today, it is 7 years later, and he is swimming with his kids, he is 

walking 5 kilometer (5k) races, and he has seen no decline at all 

in his respiratory function. Ted and 31 other Americans have been 

lucky enough to try this cutting-edge therapy. But, in the years 

since that clinical trial began, 24,000 other Americans with Lou 

Gehrig’s disease have passed. 

The problem is the FDA’s extremely long and archaic process for 

approving treatments—especially for people with terminal diseases. 

It takes on average 15 years to bring one of these new drugs to 

market. 

During the course of writing my book, someone who has become 

a friend of mine, Jenn McNary—she is the mother of two brothers 

with Duchenne’s Muscular Dystrophy (DMD)—said to me, ‘‘By the 

time this drug that we need is on the market, we are going to lose 

an entire generation of boys.’’ Fifteen years of delay at the FDA is 

an entire generation of boys lost. It is unethical not to give these 

boys a chance at life. 

It is also unconstitutional. In America, today, terminal patients 

have the right to hasten their deaths through ‘‘Right-to-Die’’ laws, 

but they do not have the right to try to fight to live. So you can 

get drugs to die, but not if you want to save your life. 

And that is why the Goldwater Institute designed what we call 

‘‘Right-to-Try’’ laws. And, as of today, 24 States—including 7 of the 

home States that members of this panel represent—have adopted 

the ‘‘Right to Try.’’ And that is passing on a 99–1 vote margin. 

Under these laws, if you have a terminal diagnosis and the FDAapproved treatments are not working for you, you have the right 

to try to save your life by taking some investigational medicines 

that are under study at the FDA, but may still be 10 years, or even 

15 years, away from getting that final green light. 

These ‘‘Right-to-Try’’ laws are not a panacea. They will not help 

every patient. But, at least they move us in the right direction. I 

know of 28 patients that are being treated under the laws at this 

time and I know that lives, in fact, are being saved. 

There are two key reforms that you can move in Congress that 

will help millions access some of these life-saving drugs. 

The first is that Federal law should clearly let doctors prescribe 

drugs to terminal patients after they have passed ‘‘Phase 1’’ safety 

testing. Terminal patients simply do not have time to wait for efficacy tests. 

Second, an estimated 30 percent of the newest advances in medicine are first available overseas—as you will hear in Diego’s story. 

These drugs, that have already received the green light from countries like Germany and Japan, should be available to patients here 
6 

1The prepared statement of Ms. McLinn appears in the Appendix on page 88. 

in the United States. This would bring proven life-saving treatments to patients in America, now. 

If you were on a sinking ship—or your spouse or your child— 

would you pass on the only available lifeboat because the government had not certified it yet? 

As a society, we can and we should debate the best ways to make 

better and stronger lifeboats. But there is no argument for withholding the lifeboats that we do have from people who are drowning. So, please, help us loosen the ropes and let us get the lifeboats 

in the water. 

Thank you. 

Chairman JOHNSON. Thank you, Ms. Olsen. 

Our next witness is 6-year-old Jordan McLinn, who brought 

along his Mom, Laura McLinn. Ms. McLinn is the owner of Indy 

Learning Center, founded in 2005, and the mother of three—including Jordan. She received her bachelor’s degree in elementary 

education from the University of Indianapolis and a master’s degree in education from Indiana University. She is a former junior 

high school and high school math teacher. 

Ms. McLinn and Jordan. 

TESTIMONY OF LAURA MCLINN,1 INDIANAPOLIS, INDIANA 

(ACCOMPANIED BY JORDAN MCLINN) 

Ms. MCLINN. Thank you, Chairman Johnson and Ranking Member Carper. I really appreciate you allowing us to be here today. 

I am going to let Jordan just say a word here, and then, if it is 

OK, I am going to just send him out with Erica to play, but I want 

to make sure that he has a turn to speak here. Go quickly. What 

do you want to say? 

Master MCLINN. Please say yes for the drug. 

Ms. MCLINN. OK. 

Master MCLINN. Watch this, Daddy. 

Chairman JOHNSON. I think he is, Jordan. [Laughter.] 

Thank you, Jordan. We appreciate it. 

[Applause.] 

Ms. MCLINN. About a year ago around this time, Jordan and I 

were in the State of Indiana, and we were testifying together for 

the ‘‘Right-to-Try’’ legislation, and Jordan stood there, and he said 

to them, ‘‘Please say yes.’’ 

This year, he is a year older, and the things that I am going to 

tell you I do not, necessarily, want his ears to hear this time, so 

I want to start by just telling you how special Jordan is. You see 

him. He is six. He is running around here like he owns the place. 

He sat right up there in that chair. And, that is what he does. He 

is really smart. He plays. He hugs me. He climbs. 

But, believe it or not, he is in a fight with the clock—and he is 

declining. At just 6 years old, he has Duchenne Muscular Dystrophy, just like you heard about earlier, about Jenn’s boys. Jordan 

has the same disease. It is 100 percent fatal. Most boys live to be 

around 20. Some make it a little longer; some do not make it that 

long. 
7 

So, he is in the physical decline phase now, which means that 

he is losing function—and, with muscle disease, when that starts 

to happen, you just do not get that back. It is a little different from 

maybe cancer and some other diseases where, maybe when you are 

on your deathbed you can take a medication, and then, maybe, you 

can live a long, full life. 

For Jordan, it does not work that way. We cannot wait 15 years 

and then give him these drugs that are coming up through the 

pipeline for him. There are exon-skipping drugs that are working, 

that exist. So, for the first time in the history of this disease, there 

is something that can help Jordan. 

When I was in Ohio testifying for ‘‘Right to Try,’’ I actually 

talked with them about changing the language in their bill there 

because they defined ‘‘terminal’’ as, I believe, maybe 6 months or 

a year to live. Well, Jordan’s disease is terminal, and when he is 

at the point where maybe he has 6 months to live, it is going to 

be too late for him to receive the treatments that are existing, that 

are coming up. 

So what I would like to say to you today is that Jordan—there 

is a drug there. Jordan needs it now. I do not know the best way 

for him to get that. When we testified for ‘‘Right to Try’’ and it was 

passed in the State of Indiana, we were given kind of a whole new 

layer of hope—kind of like a backup plan. But, ideally, we want 

Jordan to get this drug because the FDA approves it, because it 

works. We do not want them to wait 15 years to approve it because 

we do not have that kind of time. 

Back in 2012, you passed the Food and Drug Administration 

Safety and Innovation Act (FDASIA). The President signed that 

into law in 2012. And prior to that, I am sure that you remember 

when acquired immunodeficiency syndrome (AIDS) was very scary 

and everyone was so afraid that so many people were going to 

die—and the FDA acted very quickly and they started approving 

things quickly. And they should have. And now you do not hear 

that much about it, right? Because there are so many drugs out 

there that are helping patients with human immunodeficiency 

virus (HIV) and AIDS. 

Well, in 2012, the President signed FDASIA. FDASIA says that, 

‘‘Hey, this should not just apply to something like that. It should 

also apply to rare disease.’’ So you gave the FDA the authority to 

say, ‘‘It is OK to do a smaller trial, it is OK to do accelerated approval, and it is OK to do that for these boys, like Jordan, that 

have rare diseases.’’ We might not find 500 people to do a trial for 

a disease like what Jordan has. There might not be that many patients out there. But, right now, at the end of May, the FDA has 

a decision to make about an exon-skipping drug. They are going to 

decide yes or no. They are going to say yes or no to Jenn’s sons, 

who are on this drug that you heard about earlier. 

In this trial, there are 12 boys. So that is a small group, right? 

The FDA does not like that. But there are 12. There are 12 in this 

trial. The 4-year data showed that 10 of those 12 boys are still 

walking. In the external control group that had 13 boys—the same 

ages, with the same mutation, and receiving the same steroid regimen—one of the 13 is still walking after 14 years. That should tell 
8 

1The prepared statement of Mr. Morris appears in the Appendix on page 91. 

everyone in this room something, right? That drug is working for 

these boys. 

But, we are not getting a good feeling right now from the FDA 

that we are going to hear yes at the end of May. We are hopeful. 

It is the right thing to do. They have the authority to say yes. You 

have given them that power. So, I am not asking even for any new 

legislation—although I believe in ‘‘Right to Try’’ and I think that 

there is definitely a place for that. It might not work for Jordan 

today, but there are lots of cancer patients and ALS patients that 

‘‘Right to Try’’ works for. I believe in that. 

But I also believe that the FDA needs to use the power that they 

already have been given, by you, to say yes and give accelerated 

approval to drugs that are working, that are safe, and that are effective. And boys like Jordan—all of these boys deserve that 

chance. 

So I urge you to urge the FDA to use the tools and the power 

that you have given them to say yes. 

Chairman JOHNSON. Thank you, Laura, and, obviously, we hope 

that they say yes. 

Ms. MCLINN. Thank you. 

Chairman JOHNSON. Our next witness is Diego Morris. Diego is 

a 15-year-old honor student at Brophy College Preparatory and 

previously a student and student body vice president at All Saints 

Episcopal Day School. He is also a cancer survivor and, at the age 

of 13, was honorary chairman of the ‘‘Right to Try’’ initiative in Arizona. Diego. 

TESTIMONY OF DIEGO MORRIS,1 PHOENIX, ARIZONA 

Mr. MORRIS. Good morning, Mr. Chairman and Members of the 

Committee. Thank you for inviting me to testify. I am incredibly 

honored to be with you today. 

Four years ago, I was a typical 11-year-old boy. I was playing 

two sports at the time—baseball and soccer. One morning, I woke 

up with pain on the outside of my left knee. I thought that it was 

just a typical sports injury. I continued to play in my games, and 

I did everything as usual for a few days. But the pain would not 

go away and it was causing me to limp. My mom took me to the 

pediatrician—and thank goodness my doctor knew immediately 

that something was not right. She sent me to an orthopedic surgeon the following day for an X-ray. The doctor told my mom that 

he believed I had osteosarcoma, a rare type of bone tumor, just by 

looking at my X-ray. 

Everything happened quickly after that appointment. My parents 

consulted with many of their physician friends about what we 

should do next. My parents took the advice of our close family 

friends. He is a radiation oncologist and she is a pediatrician. They 

told my parents that I needed to have a biopsy as soon as possible 

at a premier research institution. 

Just 3 days after my trip to the pediatrician, we were on our way 

to St. Jude Children’s Research Hospital (St. Jude) in Memphis, 

Tennessee. We never stopped hoping that I did not have cancer. 

After a long week of different types of tests and scans, they per-
9 

formed a biopsy. We knew the surgeons would be looking at a quick 

type of analysis that they perform in the operating room. If the 

surgeons determine that it is cancer at that point, they go ahead 

and place a port in the patient’s chest. When I had barely come out 

from anesthesia, I asked my parents, ‘‘Do I have a port?’’ They answered, ‘‘Yes.’’ The three of us cried—and my life was never the 

same again. 

After many conversations with physicians, we decided that I 

should start chemotherapy back in Phoenix. My parents came to 

the conclusion that, if I would receive the exact same pre-surgery 

chemotherapy in Phoenix, I should be home and in my own bed as 

much as possible, surrounded by the family and friends who love 

me. I received chemotherapy for 10 weeks at Phoenix Children’s 

Hospital before returning to St. Jude for limb salvage surgery. I am 

so grateful that the surgeons were able to save my leg and completely remove the tumor. They inserted a significant titanium device in my leg, which partially replaced my femur and my knee. 

After surgery, the analysis of the tumor indicated that the necrosis, or the amount of the tumor killed by the initial chemotherapy, 

unfortunately, was only 50 percent. The doctors were hoping to see 

at least 80 percent necrosis. This meant that I would have to have 

a very aggressive plan of treatment. I needed a total of 21 rounds 

of chemotherapy, with some of the strongest chemotherapy drugs. 

Thank goodness that my parents’ physician friends never stopped 

doing research on every available treatment for me. They told my 

parents about a drug called Mifamurtide. Mifamurtide is an immune therapy drug that has improved survival rates for children 

with osteosarcoma. My parents were excited about the drug, but 

they quickly realized that it was not approved in the United States. 

Mifamurtide was available in so many countries all over the world, 

they were astonished that it was not available in America. The 

trials for Mifamurtide had actually been started by physicians in 

the United States. My parents flew to Mexico City with our friend 

who is a pediatrician to see the results of Mifamurtide on their 

osteosarcoma patients. The doctors there showed them their findings and told my parents that I was welcome in their hospital to 

receive Mifamurtide. 

The clock was ticking. In order to have Mifamurtide immune 

therapy, I had to start it at the exact same time as my post-surgery 

chemotherapy—just 10 weeks after undergoing surgery at St. Jude. 

My parents never gave up hope that they could get this treatment 

in the United States. They contacted our Congressman, the FDA, 

the drug manufacturer, and anyone who they thought could help 

us find a way. They even spoke with the lead physicians for the 

U.S. trials at the University of Texas MD Anderson Cancer Center 

(MD Anderson) and Memorial Sloan Kettering Cancer Center 

(Sloan Kettering). The doctor at Sloan Kettering explained 

Mifamurtide and answered all of my parents’ questions. My parents told him that they were not looking for guarantees—just hope. 

I will never forget my parents and their friends explaining to me 

and my brother that we were going to move to London so that I 

could have Mifamurtide treatment along with my chemotherapy. 

We were so upset with my parents, at first, but, ultimately, we ac-
10 

1The prepared statement of Dr. Gulfo and attachments appears in the Appendix on page 94. 

cepted that this might help to save my life. Our entire family left 

our home in Phoenix, Arizona and moved 5,000 miles away. 

My chemotherapy treatment was brutal, and I was in the hospital more often than not. My dad was always exhausted and hated 

not being with us. My mom was exhausted, too, going back and 

forth between the hospital and home to take care of my brother 

and I. 

But, there is no place like home. I felt so isolated. I missed my 

friends, my home, my dog, and my school. 

My family and I were very fortunate to have the resources to relocate to another country. Most people do not have that option. 

When my family and I returned to the United States, we all agreed 

that we would do anything to help other families to not have to go 

through what we did to get this treatment—or, worse, to not have 

a promising treatment at all. So, when the Goldwater Institute 

asked me to serve as honorary chairman of the ‘‘Right-to-Try’’ campaign in Arizona, I jumped at the opportunity. I am grateful to 

Darcy Olsen and the people at the Goldwater Institute for giving 

me the chance to do something positive with my terrible experience. I am grateful to be alive, and I am grateful to be here with 

your esteemed Committee today. 

I hope and pray that we can make it easier for Americans to 

have faster access to critical medical treatment. Please help us give 

Americans a better chance to save their own lives and those of 

their loved ones. No guarantees—just hope. 

Thank you very much. 

Chairman JOHNSON. Diego, I have to just quickly ask now, have 

you been judged cancer-free? 

Mr. MORRIS. Yes. 

Chairman JOHNSON. For how long? 

Mr. MORRIS. It has been about 3 years. 

Chairman JOHNSON. OK. Thank you for your testimony. 

Mr. MORRIS. Thank you. 

Chairman JOHNSON. Our next witness is Dr. Joseph Gulfo. Dr. 

Gulfo is executive director of the Rothman Institute of Innovation 

and Entrepreneurship at Fairleigh Dickinson University, at which 

he is spearheading the Initiative for Patient-Centered Innovation. 

He is also visiting scholar at the Mercatus Center of George Mason 

University and the author of ‘‘Innovation Breakdown.’’ Dr. Gulfo received his Doctor of Medicine (M.D.) from the University of Medicine and Dentistry of New Jersey and his Master of Business Administration (MBA) from Seton Hall University. He was responsible for the approval of an antibody for prostate cancer, a bladder 

cancer drug, and a medical device for melanoma detection. Dr. 

Gulfo. 

TESTIMONY OF JOSEPH V. GULFO, M.D.,1 EXECUTIVE DIRECTOR, ROTHMAN INSTITUTE OF INNOVATION AND ENTREPRENEURSHIP, FAIRLEIGH DICKINSON UNIVERSITY 

Dr. GULFO. I would also like to note that I submitted a fuller, 

written statement, a book excerpt, and other writing to the record 

that I would like to be submitted. 
11 

Chairman JOHNSON. It will be entered. Thank you. 

Dr. GULFO. Thank you very much. 

Well, thank you very much for inviting me to participate in this 

hearing. As Chairman Johnson and my fellow witnesses eloquently 

explained, ‘‘Right to Try’’ is an especially important concern for patients and their families—particularly those for whom no approved 

options exist and who are terminally ill. 

The ‘‘Right-to-Try’’ debate also vividly illustrates several 

foundational principles contained in my research about the proper 

role of the FDA for the 21st-Century medical ecosystem, which 

apply to patients at all stages of their disease—not just terminally 

ill or those with no good choices. 

I have six brief points to make. 

First, the FDA has substituted its statutory mission to promote 

health with a new, misperceived duty to protect health, virtually 

at any cost. When terminal patients have no other options, what 

is the FDA protecting when it prohibits access to experimental 

treatment? The potential harms of the FDA’s approach to protecting health are not limited to terminal patients, however. It has 

serious implications for all who suffer disease—and it is having a 

chilling effect on medical innovation. 

Second, benefit versus risk is a private health decision requiring 

the consideration of the individual’s needs. The FDA’s reliance on 

the benefit versus risk to the average patient is not an acceptable 

substitute. ‘‘Right-to-Try’’ patients seeking experimental therapies 

have a right to make these decisions, and patients and their doctors know far more about their specific circumstances than the 

FDA ever could. Of course, the same is true for all patients at all 

stages of disease. 

Third, the FDA’s restated mission to protect, rather than to promote health has necessarily made it judge new drugs and devices 

not on safety and effectiveness—as specified in the law—but, rather, on clinical utility, benefit versus risk, and long-term outcomes, 

including survival. This truly stifles medical innovation by necessitating larger and larger and longer and longer trials that are extremely expensive. The net result is that many compounds, which 

could possibly help patients, are not even developed—and many 

that are obviously safe, effective, and could be helpful actually fail 

in these kinds of trials because the studies are improperly structured. It is simply impossible to control for all of the variables that 

modulate long-term outcomes. 

Fourth, increasingly the drugs that are developed, even by large 

companies, are geared toward narrow, niche, and orphan populations, where benefit versus risk is a low bar because there are no 

other products available. In 2014, 40 percent of all new drug approvals were for orphan claims. In 2015, the number jumps to 48 

percent. 

Fifth, the very fact that we are here, today, to discuss this magnificent movement is testimony to the sophistication of today’s 

medical ecosystem and marketplace. That which we may have 

needed the FDA to do just a few years ago is unnecessary today. 

With the Internet and rapid communications among patients and 

among physicians, knowledge is shared at a lightning pace. Patients have easy access to timely, high-quality information that al-
12 

1The prepared statement of Ms. Goodman appears in the Appendix on page 187. 

lows them to make excellent treatment decisions with their doctors. 

Today’s reality could not have been anticipated 20-plus years ago, 

when the FDA began to move away from safety and effectiveness 

as the rightful basis for approval. 

My final point is that medical innovation is fragile because most 

of it occurs in small start-up companies. I have been responsible for 

the development and approval of products for prostate cancer, bladder cancer, and melanoma. As such, I have worked very closely 

with all three of the FDA centers—drugs, biologics, and devices— 

in the development of novel products. The two things that start-up 

companies need the most are investment and regulatory certainty. 

Two companies that I ran no longer exist because the FDA changed 

the criteria for approval after we performed large studies that 

achieved all of the endpoints to which the FDA agreed before we 

started. In both circumstances, the FDA told us that safety and effectiveness were not enough—rather, clinical utility and evidence 

concerning long-term outcomes were required. This made investment disappear and rendered it impossible for us to launch the 

products and bring them to doctors and patients effectively after, 

ultimately, obtaining the approval with no new data in either case. 

In summary, the need for the ‘‘Right-to-Try’’ movement is emblematic of the FDA’s ‘‘protect health at all costs’’ ideology. This 

has made the FDA assume a role that it was never intended to 

have—being arbiters of benefit versus risk, clinical utility, and 

long-term outcomes—and that has brought the FDA into private 

health decision-making. We need the FDA to return to its public 

health mission of promoting health by making approval decisions 

on the basis of safety and effectiveness. 

Thank you. 

Chairman JOHNSON. Thank you, Dr. Gulfo. 

Our final witness is Nancy Goodman. Ms. Goodman is the executive director of Kids v Cancer, which she founded in memory of her 

son, Jacob, a victim of pediatric cancer. Her group focuses on encouraging pediatric cancer research and pediatric, rare disease 

drug development. Ms. Goodman. 

TESTIMONY OF NANCY GOODMAN,1 EXECUTIVE DIRECTOR, 

KIDS V CANCER 

Ms. GOODMAN. Thank you, Chairman Johnson, Ranking Member 

Carper, and Members of the Committee for inviting me here today. 

I am honored to testify before you about how to connect patients, 

and children in particular, to new and potentially life-saving treatments. 

I am the executive director of Kids v Cancer. But, more importantly, I am the mother of Jacob, who was a beautiful, normal, 

loud, difficult, and brilliant little boy at 8 years old, who was diagnosed with brain cancer. Jacob suffered 2 years of profound neurological impairments and unmanaged pain before he died at age 10. 

I have been working at Kids v Cancer now since Jacob died 7 

years ago, and, frankly, I do not even like speaking about him in 

public anymore. It is too raw. But, I brought a photo so that you 

can emotionally connect that way. 
13 

The fact is that the drugs that were used to treat Jacob were 40 

years old, and so for this reason, I launched Kids v Cancer to focus 

on changing the landscape of pediatric cancer research and to make 

it possible for children to get access to novel treatments. 

When Jacob was at the end stage of his cancer, I contacted eight 

separate companies, who were in the process of adult clinical trials 

for brain cancer drugs, to request access to these unapproved drugs 

for Jacob. Finding the right person to speak with was very difficult. 

Sometimes I contacted the CEO, others times the Chief Medical Officer (CMO) or the head of business development. For one company, 

it was a friend of my cousin. It was all very ad hoc. Of the eight 

companies, six did not ever respond to my request and made no determination. Two formally reviewed it and declined. And then, 

Jacob died. 

So the purpose of the ‘‘Right-to-Try’’ laws is to help patients get 

access to drugs that they would not otherwise get access to. That 

is a serious problem, and it is a goal that I share. But I think that 

we need to take a broader approach to this problem, and that has 

been the focus of Kids v Cancer. 

The fact is that children with cancer seek compassionate use access to drugs because there are almost no clinical trials available 

to them of these same unapproved drugs. Kids have to wait until 

drugs are approved, when they have cancer, before they get access 

to them in a clinical trial setting. 

So our first step at Kids v Cancer was to incentivize companies 

to develop drugs specifically for pediatric cancers and other pediatric rare diseases. In 2012, Congress passed the Creating Hope 

Act as part of the Prescription Drug User Fee Act (PDUFA). That 

has created nearly $800 million in incentives—at no cost to the taxpayer—for companies that get a new drug for pediatric rare disease 

approved by the FDA. The Creating Hope Act is doing what everyone hoped: stimulating companies to turn advances in science into 

treatments for pediatric cancer. 

The medical challenges are hard enough to overcome. Kids with 

cancer should not be disadvantaged by the lack of economic incentives for companies to develop drugs for tiny markets. The Creating 

Hope Act is up for renewal as part of the 21st Century Cures Act 

passed by the House, and I urge the Senate to pass it as well. And 

I am also proud to say that several of the drugs developed for 

Duchenne Muscular Dystrophy are benefited and supported financially by this legislation. 

Our second step with Kids v Cancer was to make new drugs 

being developed for adult cancers available for kids as well. In 

2003, Congress passed the Pediatric Research Equity Act (PREA), 

which requires companies developing drugs for adults to conduct 

pediatric trials on such drugs where they could benefit children. 

The problem is that PREA has not kept up with the science. PREA 

only requires clinical trials if the children have the same ‘‘indication’’—that is, if children have the same kind of cancer. But now, 

we know that children do not get breast cancer or prostate cancer, 

but the mechanism in these cancers might be evident in pediatric 

cancers such as neuroblastoma or medulloblastoma—the type of 

brain cancer that my son had. 
14 

We have proposed the Kids Innovative Drugs (KIDS) Initiative, 

a modest change to PREA that would update PREA to take into account these new scientific developments and ensure that drugs 

being developed for adults, which could have relevance to pediatric 

cancers, are tested on children as well. And I urge Congress to take 

up and pass the KIDS Initiative as soon as possible. 

We are exploring other ideas related to eligibility for trials as 

well. For example, why do almost all adult cancer trials use 18 

years of age as the minimum age of eligibility without any discussion of the scientific or medical rationale for this cutoff? 

And that brings me to ‘‘Right-to-Try’’ laws. Yes, when it comes 

to seeking compassionate use access to unapproved drugs, the paperwork is onerous and the process is time-consuming. In response, 

Kids v Cancer is launching a ‘‘Compassionate Use Navigator.’’ We 

are working to better inform physicians on how to apply for compassionate use applications for their pediatric cancer patients with 

drug companies, the FDA, and their hospitals. We hope to provide 

point of contacts (POCs) for drug companies. We will post the FDAs 

new, expanded access form and we will work with the Institutional 

Review Boards (IRBs) of the hospitals where the children are treated. We will offer to counsel physicians, personally, on specific applications. In addition, we will collect information about the efforts 

and the outcomes of pediatric cancer compassionate use applications. 

The ‘‘Compassionate Use Navigator’’ is not the whole solution to 

the challenge of connecting children with cancer to new treatments. 

However, it will give parents of dying children more time with 

their kids. It will lessen the burden that their physicians have as 

they apply for compassionate use applications. And, we hope that 

it will encourage more physicians of kids with cancer to apply for 

compassionate use. 

In addition, Kids v Cancer supports the Andrea Sloan Compassionate Use Reform and Enhancement (CURE) Act to have drug 

companies make available to the public their policies on requests 

for compassionate use access, including the minimum criteria for 

approving requests and the time needed to make a decision. I urge 

the Senate to pass the Andrea Sloan CURE Act as part of the 21st 

Century Cures Act bill as well. 

But, from my personal experience and from working with dozens 

of other families, my sense is that the fundamental problem is not 

the FDA, but, rather, it is the incentive facing companies. Even 

though the FDA approves virtually all compassionate use applications that it receives, and even though it has indicated that an adverse reaction to a drug provided for compassionate use will not adversely affect a company’s application for that drug’s approval, 

companies remain risk averse—and they would rather not provide 

such drugs. 

But, even if one could change that, the results would be one-off 

anecdotes. We cannot afford to take an ad hoc approach to addressing pediatric cancers and pediatric rare diseases. We need to address the lack of access that seriously ill children have to novel, unapproved drugs not only by one-off compassionate use applications, 

but also in clinical trials. That is why initiatives such as the Creating Hope Act and the KIDS Initiative are so important—they 
15 

give companies compelling economic reasons to create new drugs 

for kids and require them, where appropriate, to study pediatric 

uses of drugs that are being developed for adults. And that makes 

it easier for children to get access to drugs that they need to survive and live happier, healthier lives. 

We need more, however, than anecdotes. We need to change the 

landscape of pediatric cancer, and we need to ensure that children 

with rare diseases—life-threatening diseases—like Jacob, Diego, 

and Jordan, will have access to new and potentially life-saving 

treatments. 

Thank you. 

Chairman JOHNSON. Thank you, Nancy. Obviously, we are sorry 

for your loss. 

I do want to go right to you—and possibly Dr. Gulfo will also answer the question. Why is it that kids are not involved in clinical 

trails? I mean, how else do you test these things? You kind of 

asked the question. Do you not have the answer? Do you have suspicions? Or, maybe, we will push it over to Dr. Gulfo to answer 

that question. 

Ms. GOODMAN. I have my theories as well as to why companies 

are reluctant to undertake pediatric clinical development. First of 

all, the markets are small. It is very tough to develop a drug for 

a very rare disease, whether it be pediatric medulloblastoma or 

Duchenne’s Muscular Dystrophy. Accrual rates are small. It is just 

challenging to put a drug together, and what that means is that 

the drug that you develop has to really be very good—and that is 

difficult. 

Chairman JOHNSON. So, is that a company decision or is that an 

FDA decision? 

Ms. GOODMAN. That is a business decision. 

Chairman JOHNSON. A business decision. So, there is no law that 

prevents children from being involved in clinical trials? 

Ms. GOODMAN. Well, that is correct. And for that reason, Congress passed the Creating Hope Act in 2012. 

The second reason that I think it is difficult is that companies 

maximize return on investment (ROI) over the long run through 

blockbuster drugs, and undertaking a pediatric trial is just a distraction for them if their goal—for which they have fiduciary responsibility to shareholders—is long-run return on investment. 

There are two laws that Congress has passed to address this problem. One is PREA, which I discussed, and the other is the Best 

Pharmaceuticals for Children Act (BPCA). The problem with PREA 

is that it does not apply to cancer. PREA requires companies to undertake certain pediatric trials and BPCA does provide a carrot, an 

incentive for companies to provide such trials. 

The challenge with BPCA is that it is entirely optional. Companies do not have to undertake these trials until the time that it 

makes the best business decision, the most sense for them, from a 

business perspective—which is the very end of their exclusivity period. So the National Organization for Rare Disorders (NORD) has 

estimated that that is 91⁄2 years after approval of the drug for adult 

indications. 

Chairman JOHNSON. Dr. Gulfo, do you have anything to add to 

that? 
16 

Dr. GULFO. Yes, I will add. Cancer is a disease of the elderly. I 

mean, I teach cancer biology, and in order to accumulate the 

mutations that you need, you need to live a long time. So, I could 

not agree more with what Nancy said. So, it is a very small market 

for pediatric cancers. I think that that is a critically important 

thing. The other is that—— 

Chairman JOHNSON. But, I just want to—because, one of the 

things in your testimony that you talked about was the innovation 

occurring in orphan diseases—limited use targeted. So, can you explain that for me? 

Dr. GULFO. You took the words out of my mouth. As we continue 

to see companies going for these ultra niche claims, you are going 

to get to the population sizes for pediatric cancer. So, I actually 

think that we are going to see more of that. 

It is also very hard to do studies in children—very hard. The 

level of approvals that you need and the way that they are looked 

at—the way that they are looked at by the IRBs and things, it is 

very difficult because you have patients who are young and who 

could, potentially, live a very long time. So, it is harder to do. The 

market is not there. But, I agree with you, as this progress is 

pushed to more and more niche claims, you will see more and more 

childhood cancer studies. 

Chairman JOHNSON. With my questions, I am really going to be 

talking about the impediments. I think that I said earlier ‘‘legitimate’’—I will say ‘‘understandable’’ problems. And I thought that 

your testimony was really pretty interesting. Part of the problem 

has been things, like congressional hearings, where we call members of the FDA up here, and if it has not been perfect—let us face 

it, life is full of risk. There is no such thing as a risk-free society. 

Members of Congress beat up on the FDA, and so, they become 

even more risk averse. So, I want to concentrate on that. 

Darcy, I do want to talk to you, though, because you talked about 

Ted Harada, but you mentioned 31 other people with that same 

exact drug. I am afraid that I know what the result was for the 

other 31. Did they pass? 

Ms. OLSEN. To my knowledge, most of them actually did quite 

well. 

Chairman JOHNSON. So, they extended their life, but, I mean, 

have they all passed or—— 

Ms. OLSEN. No. No, they have not all passed. 

Chairman JOHNSON. OK. So we have more than one Lazarus 

then. 

Ms. OLSEN. Yes, we do. 

Chairman JOHNSON. OK. 

Ms. OLSEN. And so, for that particular treatment, they are in 

Phase II and III. They are doing all kinds of tests. But even someone like Ted—it is interesting, when you talk about wanting to get 

into clinical trials, Ted actually no longer qualifies for the next clinical trial. So, if the treatment wears off for him, he could still die 

from—— 

Chairman JOHNSON. And he had access to this when? 

Ms. OLSEN. About 7 years ago. But now, he is disqualified for the 

next—— 
17 

Chairman JOHNSON. I cannot imagine having a family member 

with ALS, knowing that 7 years ago somebody was surviving this, 

and not having access to it. I mean, Doctor, can you explain that? 

Can anybody explain? Again, I am not beating up on anybody. 

Please explain why something that could be that great a breakthrough, in a disease that we all know the end state of, is not made 

available. Why don’t we just rush that? Please explain that. 

Dr. GULFO. I cannot. I mean, are the trials still ongoing? 

Ms. OLSEN. Yes. 

Dr. GULFO. And he does not meet the entry criteria? 

Ms. OLSEN. Yes. 

Dr. GULFO. Right, so the entry criteria would need to be amended for him, and there is a mechanism in place for compassionate 

use in order to do that. But, I think that what people are asking 

here is, why do we need to go through so many hoops? 

Chairman JOHNSON. Ms. McLinn, you were talking about some 

drugs that really address—maybe not specifically your son’s condition, but certainly would tie into a potential cure as well. Talk 

about that, the impediments to compassionate use. What are you 

finding to be the barriers? 

Ms. MCLINN. Well, first of all, it does apply to Jordan, and it is 

kind of confusing, but the drug that is up for accelerated approval 

is a drug that 13 percent of boys with Duchenne are—they can benefit from this drug. The drug that Jordan needs is the very next 

one in the pipeline. In fact, it works the same way. The chemical 

backbone is the same. It is made by the same company. But we 

need approval for this one in order for Jordan’s to move forward. 

Chairman JOHNSON. And it just addresses a different part of the 

gene? Is that the—— 

Ms. MCLINN. That is right. 

Chairman JOHNSON. So how many children—how many young 

boys—has this actually helped, to date, that have had—and how do 

they get access to it? Was it through a clinical trial? Was it 

through compassionate use? Was it a one-off? 

Ms. MCLINN. Only through a clinical trial, not through compassionate use at all. So, there were 12 boys in the original trial for 

the drug that skips Exon 51, but they are now doing confirmatory 

trials. I cannot give you an exact number, I am sorry, but there are 

a lot more boys now who are receiving that drug. 

Chairman JOHNSON. Is it tens? Is it hundreds? 

Ms. MCLINN. Hundreds? Hundreds. 

Chairman JOHNSON. Hundreds—but there are thousands with 

the disease. 

Ms. MCLINN. Oh, yes. Yes. And the thing is that 1 in 3,500 boys 

have Duchenne, and so, within that 1 in 3,500, 13 percent of boys 

can take this drug that I was speaking about—that the FDA is 

going to say yes or no to. And then, 8 percent of boys have the mutation that Jordan has and 8 percent have another mutation. And 

then, it just keeps going down the line there. But we are talking 

still about a lot of boys that are waiting on this treatment. It exists. And I will tell you that there are boys in Europe who are receiving the drug that Jordan needs. I know one of them, personally. 

He is jumping. That does not happen. Jordan cannot jump. This 
18 

1The fact sheet referenced by Senator Carper appears in the Appendix on page 209. 

does not happen in this disease. These drugs are working. So, there 

are boys on this drug in Europe—just not here, yet. 

Chairman JOHNSON. So just real quickly, before I turn it over to 

Senator Carper, Dr. Gulfo, is there any rationale for not—I mean, 

again, is there any rationale for not allowing parents, and their 

children with this disease, to have access to this drug now? 

Dr. GULFO. Well, there is rationale not to approve it, but—until 

there is proper evidence. Now, my whole testimony is about defining what ‘‘proper’’ is, OK? But having them have access—absolutely, they should have access to it. These children, as you said 

earlier, their diseases are terminal. It is terrible. 

Chairman JOHNSON. But, again, I do want to get the other—the 

companies, themselves, are concerned about having an adverse result—— 

Dr. GULFO. Absolutely. 

Chairman JOHNSON [continuing]. In a nonclinical trial, or whatever, and having that affect the ability to—and we all ought to be 

concerned about that, because, if there is a drug that could be helpful and it gets, basically, kiboshed because of one of these compassionate use—— 

Dr. GULFO. Right. So, why would the company do all of the 

things that you need to do to show that it is safe to give to the 

child in that case, OK, when it is just pure risk? Because if an adverse event were to happen—and adverse events happen—it will 

directly impact the development program and hurt many other 

children. I mean, you look back at it, this could really hurt the 

availability of this drug for many others. So, I could not agree more 

with what Nancy said—although the right things are said, it is not 

in practice. There was a company whose product was put on clinical hold because of an adverse event that happened in a compassionate use setting. The company’s name is CytRx. And that just 

should not happen—and that sent the message throughout the 

whole industry that there the risks involved in trying to be good 

citizens. 

Chairman JOHNSON. ‘‘Catch-22’’ is running through my mind 

here, as we are talking about this. 

Dr. GULFO. Yes. 

Chairman JOHNSON. Senator Carper. 

Senator CARPER. Mr. Chairman, one concern that I think that we 

are hearing here, today, is about a lack of access to information 

about which programs are available to help people who are facing 

these life-threatening conditions. Since the FDA is not with us 

today to provide information on how their current processes work, 

I just want to ask unanimous consent for the fact sheet1 that I 

have here, on patient access to investigational therapies, from the 

FDA, be included in the hearing record. 

Chairman JOHNSON. Without objection. 

Senator CARPER. Thank you. 

Thank you all for joining us today. It is wonderful testimony. 

And, Ms. McLinn, I walked back into the anteroom, behind me, to 

get a cup of coffee, and there spread out on the floor were all kinds 

of toys and a little boy having a good time with Erica, who is 22 
19 

years of age. And, I had a nice chat with them, and he seems to 

be in good hands, with you and with Erica. 

I have a question for the whole panel that I am going to ask you 

to think about—and then I am going to come back and ask it at 

the end—but I am going to telegraph my pitch. Then I am going 

to ask Nancy Goodman a couple of questions, and then we will 

come back to the whole panel. But, the question that I want you 

all to think about, in the meantime, is that there seems to be a 

general consensus that there are some improvements that are 

needed in the current process that patients use to gain access to 

clinical trials and to unapproved drugs. And, here is what my ask 

is: What actions do you think that Congress should take—that Senator Johnson and myself and our colleagues should take—either 

through legislation or through partnering with the administration, 

to improve patient access to new and potentially life-saving treatments? So think about that. And, while you are thinking, I am 

going to ask Ms. Goodman a couple of questions. 

Ms. Goodman, in your testimony—I think that it was at the end 

of your testimony—you noted that you do not necessarily believe 

that the FDA is a fundamental problem for those trying to gain access to new treatments but, rather, there are challenges that companies who are developing these new treatments face when they receive requests from an individual patient. Could you just elaborate 

on this for a moment? Does the FDA assist individuals who are trying to contact companies and seeking medical treatments? Go 

ahead, please. 

Ms. GOODMAN. So, I think that it is best that I just answer this 

from my personal experience. I am not an FDA expert nor have I 

worked at a drug company. 

When I was applying for compassionate use access for Jacob, the 

two companies who declined our requests stated that they had not 

started drug development in children and that they were just concerned about what the implications of the pediatric trial would be. 

At that time, I was like any other parent with a terminally ill 

kid. I did not know a lot of people at the FDA. I did not know how 

to contact people. Since that time, however, I have formed Kids v 

Cancer, and I am grateful that I do have an opportunity to speak 

with people at the FDA. And, I have to say that, though the systems could be better developed, I have found officials at the FDA 

to be very interested in helping families gain access to compassionate use access to drugs. 

For example, a year and a half ago, there was a little boy, Josh 

Hardy, who was seeking access to an adenovirus drug on a compassionate use access basis. It was a matter of life and death for him. 

The entire pediatric cancer community rallied around him. There 

was social media and traditional media. Kids v Cancer was not the 

leader, but we did participate. And, ultimately, my understanding 

is that the reason that he got access to the drug is that an official 

at the FDA heard a story on the Cable News Network (CNN) and 

she called the CEO of the relevant company and said, ‘‘What is 

going on?’’ And she offered to craft, with the CEO, a solution. 

So, my personal experience is that they are really very interested 

in helping—and we need to give them the support and, maybe, the 
20 

legislative authority to do more. To that extent, I support the Andrea Sloan CURE Act, which would do that. 

Senator CARPER. All right. Thank you. 

Changing gears just a little bit here, I think that you launched 

something called the ‘‘Compassionate Use Navigator’’ through Kids 

v Cancer. 

Ms. GOODMAN. That is correct. 

Senator CARPER. Could you just walk us briefly through how that 

navigator works for patients and for their families? 

Ms. GOODMAN. Absolutely. So, the ‘‘Compassionate Use Navigator’’ will be launched in April, and so, I want to talk to you about 

our plans. The first steps that we are building now on our website 

are a lot of information for physicians, so that they just have an 

easier time understanding what it is that they need to do to undertake a compassionate use application. It is very difficult for physicians, even, to figure out the necessary steps right now. We will be 

talking with them first about, for example, how to find a point of 

contact in the company to reach. If they have difficulty doing that 

or if they would like our assistance, we will take that responsibility, and we will do our best. We will help them write the letter 

to the company. We have an excellent person who we just brought 

on board, Elena Gerasimov, who will be reviewing the letters and 

providing support. Doctors may be wonderful scientists and weak 

writers. That should not be a reason that a kid does not get a drug. 

Then, we will be working with the physicians as they approach 

the FDA. We will be posting the FDA’s short form on our website 

and working with the physician—and we intend to use that form 

when we approach the FDA. 

And then, third, the IRBs of the hospitals need to be involved. 

Sometimes, the IRBs are slow. I have found that whenever I call 

the IRB officials and leave a nice voicemail on their machine, they 

decide within about 30 minutes. 

So, that is what we intend to do, and then we intend to document all of our experiences, so that the whole community that is 

interested in this issue will have some information about what is 

happening with respect to compassionate use applications in the 

pediatric sphere. 

Senator CARPER. All right. Well, thank you. I am—— 

Ms. OLSEN. Senator Carper, I do not mean to be rude and interrupt, but could I just shed a slightly different perspective on compassionate use? 

Senator CARPER. Sure, please. 

Ms. OLSEN. I really appreciate what Nancy is trying to do with 

compassionate use, because it speaks to a fundamental problem, 

which is that the FDA says that they approve 99 percent of requests, but that is because you basically have to get to the top of 

the Himalayas to be able to present your request. The truth is that 

less than 1 percent of patients who are terminally ill in this country will ever get through the compassionate use program. 

There is a principle at stake as well, which is that you should 

not have to beg the Federal Government for permission to save 

your life. This is America, and compassion should be the rule, not 

the exception to the rule. And, in working on my book, we interviewed Janet Woodcock, is head of Center for Drug Evaluation and 
21 

Research (CDER) and is acting director of CDER’s Office of New 

Drugs (OND), and asked this question to the FDA: ‘‘Do you think 

that it would be a good thing if tens of thousands of patients with 

terminal illnesses were able to access these investigational medicines that we are talking about? ’’ And, the first words out of her 

mouth were, ‘‘It would be another burden on the health care system.’’ 

A little bit of a different perspective. In Europe, they have tackled this. For 25 years, they have had compassionate use. They have 

it writ large. The problem in America is that companies do not 

have an incentive to participate. They have overcome that, in Europe, by granting provisional access, so say for these DMD drugs 

where they have trials going, they open it up to all of the kids, and 

then they monitor, in real time, what is going on so that they get 

better data. The kids get access right away, the companies can 

charge a nominal fee, and they have an incentive to participate because the regulatory steps become more clear. 

So there is a way to do this. We are 25 years behind. 

Senator CARPER. Thank you. 

Just very briefly, Ms. Goodman, would you like to respond to 

that—to what Darcy has said? Just very briefly. 

Ms. GOODMAN. So I do not have experience with the European 

system, and I will defer to Darcy on that. And, my only question 

is: What environment could we create where companies truly would 

be comfortable if they put a kid on a trial and the child died? Even 

if a company did not have to report that adverse event to the FDA, 

it gets reported in the newspapers. I think that the company would 

still be concerned. So, I do not know as much about this piece of 

it as Darcy does, but I am not sure that I understand, from the 

company’s perspective, how this really takes care of their concerns. 

And so, that is why, from my vantage point—at Kids v Cancer we 

have focused, first, on process with respect to compassionate use— 

it is only part of the answer—and, second, getting companies to 

start developing more interesting drugs in the first place. I just 

want to give an example. 

In the cancer space, there is a new kind of drug called PD–1 inhibitor drugs. It looks like these might be curative for patients with 

melanoma. It is very exciting. And, if you do combination therapies, 

the response rates are 70 percent in adult trials. It is really very 

exciting. 

There are 220 PD–1 inhibitor trials that are listed on 

‘‘clinicaltrials.gov.’’ This morning, I went to take a look at how 

many are available for kids right now that are open for enrollment. 

Three. How many are combination therapies? None. 

So, I just want to provide this as an example of how, from my 

perspective, I think, the goal is to create reasons for companies to 

start pediatric trials—get the denominator as big as possible. 

Senator CARPER. All right. My time has expired, and maybe we 

will have a second round, and I can ask—— 

Chairman JOHNSON. We will. 

Senator CARPER [continuing]. That question that I telegraphed a 

few minutes ago. Thank you. 

Chairman JOHNSON. Senator Ernst. 
22 

OPENING STATEMENT OF SENATOR ERNST 

Senator ERNST. Thank you, Mr. Chairman. And, thank you to all 

of you for—many of you traveled a long ways to get here. We are 

glad to have you with us today. 

Earlier this morning, I hopped on Facebook—and I was checking 

it out—and this is a picture of one of my best friend’s sons, and 

he was diagnosed with leukemia several years ago. And he has just 

taken the last of his chemotherapy pills. He has gone through quite 

an extensive treatment over the past number of years. And so after 

church on Sunday, we are all going to celebrate the fact that he 

is still with us. Fortunately, his family was able to use approved 

drugs and treatments. There are many families that do not have 

access to those drugs. So, we are lucky. And there are a lot of families that are not as lucky. 

And so, this is an important topic—and I know all of you have 

struggled with this issue, and we will continue to struggle with this 

issue, I think, as we work through this particular situation. 

Diego, it is great to have you here. 

Mr. MORRIS. Thank you. 

Senator ERNST. It is great to have you here. 

So we have spent a lot of time visiting about this, and I was astounded when I got the statistic—it came from the Energy and 

Commerce Committee during the House’s consideration of the 21st 

Century Cures Act, and that statistic is that 95 percent of rare diseases have no recognized treatment—so, Nancy, what you were 

speaking on just a little bit ago. And, I think that we all agree that 

gaining access to treatments is important and discovering those 

treatments is important. And, I do hope that our colleagues on the 

Senate Health, Education, Labor and Pensions (HELP) Committee 

can continue working on this and parallel medical innovation legislation that helps us to streamline processes, so that we can cut 

some of the red tape to get to these cures and to make sure that 

we are not hampering innovation that is available out there. 

For this panel, it is an important time, as we have seen development of new technology, and drugs that can cure illnesses and improve the quality of life. And, although, today, we have spent a lot 

of time talking about the FDA’s regulatory processes, especially for 

children, we also need to think ahead as well. And so, I would like 

to just step out there a little bit ahead. When we do have those lifesaving treatments in place and they are FDA-approved, can any of 

you speak to ways that we can break down the regulatory burdens 

that exist at the Centers for Medicare and Medicaid Services 

(CMS) that affect how quickly our Medicare recipients can start receiving these therapies? There seem to be barriers, not just for our 

youngsters, but also for those toward the end of life. Is there anyone that can speak to that? Dr. Gulfo, you look like you are thinking very hard about it. 

Dr. GULFO. Yes, I am. I am not an expert in that area, but to 

my understanding, Medicare patients cannot be denied approved 

drugs for approved claims. 

Senator ERNST. For approved—— 

Dr. GULFO. So, the issue is the approved claims part of it. Now, 

in pediatric cancers, there is a tremendous amount of off-label use. 

I think that it is as high as 60 percent, because the drugs get ap-
23 

proved for adults—like PD–1 inhibitors are approved for adults— 

and then it will be tried in pediatrics off-label. So, I think that that 

is something that you could look at—that, if approved drugs are 

used on-claim, they cannot be denied. It is when they are used offclaim, I think, that that could be an issue to look at. 

Senator ERNST. Very good. Any other thoughts? I know probably 

not your specific area, but—— 

Ms. GOODMAN. Senator Ernst, I think that that is an excellent 

question, and, again, with respect to children, one challenge is that, 

when drugs are approved, that is when pediatric oncologists have 

the opportunity to undertake pediatric trials. And then, the problem is that, because these are rare-disease drugs, the way that 

they get developed is by companies looking forward to the premium 

pricing of these drugs—and they price them very high. And then, 

pediatric oncologists cannot afford to buy them to undertake pediatric studies. 

So, again, they have to wait until companies decide to provide 

them a clinical supply of the drug for free—and that decision occurs when it is the right business time for that company—not when 

it is the right time for the kids. That is why we only have three 

PD–1 inhibitor trials for all pediatric cancers at this time. It is not 

the right business time for these companies to undertake these 

trials. And, again, that is why we are asking Congress to take up 

the KIDS Initiative to reform PREA, so that there are certain 

times when, if it is appropriate, companies should undertake pediatric trials. 

Senator ERNST. I appreciate that very much, and, again, my 

friend’s son and my friend’s family, they have been through a lot 

of stress already with approved drugs. I cannot imagine the 

stressors on families as they try and get into clinical trials and so 

forth. So, I appreciate it. I think that we need to have further discussion on how we streamline the process and make it easier for 

folks to get those life-saving drugs. 

So, thank you, Mr. Chairman, very much. I appreciate it. And, 

thank you to all of our witnesses. 

Chairman JOHNSON. Thank you, Senator Ernst. 

As soon as Senator Ayotte comes back, I will turn it over to her, 

but I want to keep going back to the impediments. There was one— 

Nancy, you talked about, in one instance, you contacted the FDA, 

and that official at the FDA contacted the CEO and crafted a solution. As briefly as possible, what was the crafted solution? How did 

they break through? Because I would think that that would be sort 

of the model of what we are trying to work—— 

Ms. GOODMAN. Yes. 

Chairman JOHNSON. I mean, it should not take a gargantuan 

public relations campaign to have an official at the FDA say, ‘‘Let 

us break through.’’ So what was the key? In other words, what did 

the FDA allow a company to do, so that it was not risk averse to 

actually involve that person in a trial? 

Ms. GOODMAN. The FDA suggested what is called an ‘‘expanded 

access trial’’ for that company. So, the FDA and the company crafted a new trial with 20 or 30 children—but it would be a clinical 

trial. The company would not only be obligated to report adverse 

outcomes, but could also collect efficacy data and submit that to the 
24 

FDA, too. And because it is a trial, the company has certain additional controls over how the drug is administered and who administers it. So, it was a solution that was good for both. 

And, I think that the question of when we use expanded-access 

trials is really important—and also when companies should be required to inform the FDA that someone has come and asked for the 

drug. The fact is that companies do not have to report that information to anyone right now, and so, in this particular case, 300 

people had asked the company for this drug. It is a drug to fight 

the adenovirus and other viral infections. And so, in this case, the 

drug really will keep people alive or not based on whether it is provided. And the FDA did not know. 

Chairman JOHNSON. Well, I am quite sympathetic with private 

sector businesses having kind of an adverse reaction to what the 

FDA can do to them—and trial lawyers as well. There is an awful 

lot of incentive—or disincentive for doing this, and that is what we 

are trying to break through. What are the impediments? 

Darcy, do you have a comment? 

Ms. OLSEN. Yes, I would just like to add—I mean, I feel like 

some of this conversation about the FDA is like, saying, ‘‘Let us put 

some fresh paint on an old jalopy,’’ and what we need to be doing 

is getting people to the moon. And to Senator Ernst’s question, for 

the elderly, but also for pediatric medicines, I mean, the simplest 

straight line is to adopt reciprocity with Europe. I mean, 30 percent 

of the advances are out overseas. It is—in Diego’s case, that saved 

his life. The medicine that saved his life—Europe’s like gold prize 

for the greatest advance in childhood medicine—and it has been 

over 20 years and it is still not approved here. This DMD drug is 

approved in Europe. 

I mean, for goodness’ sake, why is our market just this? Why do 

we not open it up to these countries? This child, that you were 

talking about, would have had access to those things. They are 

proven. They are proven, they are tested, and they are on the market. 

So, that is what we need to be talking about. Let us get to the 

moon. That is your real answer. 

Chairman JOHNSON. To me, that sounds like a no-brainer. Let us 

take the first steps here that are just so incredibly common sense. 

What has been the resistance to it, though? I mean, it is just so 

common sense. Why have we not done that? 

Ms. OLSEN. Well, that is a good question. I do not know all of 

the politics. There is a bill, S. 2388, right now that allows for reciprocal improvement—or, excuse me—approval. 

Chairman JOHNSON. Who is opposed to it? Literally, because I 

cannot imagine any human being taking a look at any one of these 

instances—whether it is Jacob, whether it is Jordan, or whether it 

is Diego—and not doing everything possible, on an individual basis. 

And yet, then collectively where is the resistance? Where is it coming from? 

Ms. OLSEN. My understanding is that the FDA wants total control over all of the drugs in the U.S. market. And, they want to do 

the regulatory process from beginning to end—even if that means 

an additional 15 or 20 years of studies. I think that that is where 

the problem is. And, when the lead official tells you that access to 
25 

these experimental medicines would be another burden on the 

health care system, I think that that gives you some insight, that 

sometimes—— 

Chairman JOHNSON. Are they talking about costs? That it is 

going to cost us money to save people’s lives? Is that what you take 

from that comment? 

Ms. OLSEN. Yes, it is about cost and systems instead of patients. 

And so, I think that that is the short answer. That is where the 

opposition comes from—but Congress can fix that. 

Chairman JOHNSON. Dr. Gulfo, I want you to comment on that, 

but also I want to go to your sixth point—because it is true. Innovation is fragile. 

Dr. GULFO. Yes. 

Chairman JOHNSON. Where are the breakthroughs going to come 

from? Listen, I believe in the National Institutes of Health (NIH) 

and the Center for Disease Control (CDC). Government can fund 

basic science and research. But, I also believe in the private sector 

and in innovators—individuals coming up with an idea. I supplied 

packaging in the medical device industry. There are so many practicing surgeons or physicians that have a concept and the idea for 

a medical device, and it is that little moment of enlightenment, 

‘‘Oh, if I could only do this.’’ 

So, we have to foster that. We cannot crush that. So, just speak 

to what I was just talking about. Where is that impediment? 

Where is the resistance to something that is so common sense—to 

take those first steps? And then, talk a little bit more about the 

fragility of innovation. 

Dr. GULFO. Sure. So, I could not agree more with what Darcy is 

saying about reciprocity. The FDA is afraid of companies shopping 

for the least regulatory-burdensome market and that that would be 

automatically approved in the States. So, it is nationalistic thinking there. 

Chairman JOHNSON. Well, is it nationalistic or is it the agency 

wanting control? 

Dr. GULFO. Yes, I am sorry. Agency. 

Chairman JOHNSON. OK. 

Dr. GULFO. The other thing that I will say is, I could not agree 

more with Darcy as well—look, I believe in a strong FDA. I think 

that we need an FDA. But, it takes 100 hours for a compassionate 

use process to be undertaken by a doctor. So the FDA came out and 

said that they are going to reduce that to—— 

Chairman JOHNSON. 100 hours of a doctor’s time. 

Dr. GULFO. Yes, 100 hours. 

Chairman JOHNSON. Of the practicing physician trying to save 

lives—it is taking him 100 hours. 

Dr. GULFO. Right. So, the FDA said, ‘‘We will have a new policy; 

they can do it in 45 minutes.’’ It has not been implemented. So, if 

the FDA were so helpful in the example that Nancy gave, and you 

have the guidance document written, why is it not implemented? 

I know that you know a lot about that. 

Ms. OLSEN. It has been a year, so it has taken them a long time 

to do that. But, I think the whole conversation about compassionate use is slightly misguided because it is not just Laura’s son 

that needs compassionate use. It is every single boy who has DMD. 
26 

Right? We need to bring these things to market. We need to get 

them to market faster. That is what Europe’s compassionate use 

system essentially is. It is called ‘‘provisional access.’’ So, once they 

go through safety testing and a little bit of efficacy testing, these 

drugs would be available in the United States. And because people 

could buy them, the companies would not be trying to give them 

away after spending $1.5 billion to develop them. So, they have 

more incentive to participate. And that is the problem in this country. 

Chairman JOHNSON. And your point also was just one of freedom. 

Ms. OLSEN. Yes. 

Chairman JOHNSON. We are in America. This should be the land 

of the free and the home of the brave. It should be up to patients— 

not the government to tell you what you can and cannot do—past 

a certain threshold. And, again, with what you are trying to do, you 

certainly have certain threshold levels of approval, either within 

the FDA clinical trial process or in terms of approval overseas. 

Ms. OLSEN. Correct, yes. So there is still basic safety with the 

‘‘Right to Try,’’ and overseas it is safety plus a little bit more, but 

there—instead of getting access at 15 years, you might get it at 

two, three, or four, when you are getting some results, because people—they do not have time to wait. And I think that Laura’s point 

on that—we cannot wait until Jordan is 18. He needs that, today, 

to live a full life. And there are solutions. A lot of these things are 

available overseas, and so, we need to think a little bit bigger than 

just making it a little bit easier for people to apply for compassionate use. Compassionate use should be the rule in this country. 

Do we want to be a country where we have the right to die when 

we are terminally ill? Fantastic. But what about those who want 

to fight? 

Chairman JOHNSON. Dr. Gulfo, as I recall—as I interpreted your 

testimony—the FDA was really set up almost with the presumption 

of approval, correct? I mean, if it is safe, basically, we are going 

to presume to allow doctors—physicians, who are pretty highly 

trained, are concerned about their patients, and are probably more 

concerned about an individual patient than somebody here in 

Washington, D.C.—that they have that ability to do so. Can you 

speak to that? 

Dr. GULFO. First of all, I am flattered that you read my written 

testimony because that is exactly right. The law is set up for the 

FDA to not approve if—not approve if. So, the bias in the writing 

of the law was that we want innovative drugs, we want to promote 

health, and we want to—— 

Chairman JOHNSON. But over time—— 

Dr. GULFO. So, it should be a reason not to—not a reason to promote. It should be a reason not to. It is like, when I played baseball, I was pretty good. My father said, ‘‘You are pretty good, but 

a pretty good hitter you go up to the plate saying, ‘I will swing if 

it is a strike.’ And, a really good hitter goes up to the plate and 

says, ‘I am swinging unless it is a ball.’ ’’ And that is what we want. 

We want the FDA swinging unless it is a ball. OK? And so that 

is what we want. 

Now, for little companies, back to your point—yes, the engines of 

innovation. I do not run little companies anymore, but to add some-
27 

thing that can just be pure risk, to do something that could put us 

on clinical hold, and to want to give a dying child something if we 

did not do all the kinds of work we are supposed to do to do that 

and did not get the right IRB approval and the whole bit, we are 

setting ourselves up for ruining the company—ruining the prospects of the product going forward. So there are tremendous disincentives to companies to try to help where they can. 

Chairman JOHNSON. Because we have not mentioned this yet, 

but, right now, we are talking about the disincentives for, maybe, 

having the FDA, really stop the approval process. We have not 

even talked about the trial lawyers and the liability issues here as 

well, which, Laura, I want to kind of go back to you. I would imagine that you would sign any waiver of liability toward any company, correct? 

Ms. MCLINN. Of course I would. 

Chairman JOHNSON. I would. Have you ever met a family member who would not? 

Ms. MCLINN. No. 

Chairman JOHNSON. So the liability issue should be really off of 

the table, correct? 

Ms. MCLINN. Correct. 

Chairman JOHNSON. By the way, is it largely? Does it really 

end—no, it is not. 

Dr. GULFO. No. 

Chairman JOHNSON. OK. Nancy, I know that you wanted to 

weigh in on one of these issues. 

Ms. GOODMAN. Well, thank you, Senator. Look, I think that you 

are asking exactly the right questions. And the piece of it that, 

again, I want to focus on is that drug development takes a long 

time. It takes 10 years or more. And, the question that we have 

been asking is: Once we know that there is an interesting drug 

under development, how do we get more patients that are dying on 

that drug? That is a very important question. 

But, I want to go back to the first question, which is: How do we 

get companies to develop more exciting drugs? The Creating Hope 

Act, which we put together, creates financial incentives for companies to do that. It is going to markup on March 9 in the HELP 

Committee, and I hope the Senate will consider reauthorizing it on 

a permanent basis. Companies need long-term assurances that this 

incentive will be there for all 10 years of its development. I am concerned that a short renewal period will not create the proper incentive. 

Chairman JOHNSON. The free market provides an awful lot of incentives. Doctors, themselves, want to create the cures. I am not 

sure government is going to be able to dictate a proper incentive 

better than what the free market actually does. So, from my standpoint, how do we get rid of the impediments? How do we reduce 

the disincentives? Because I think that there are plenty of incentives, just from a standpoint of humanity and compassion and doctors trying to cure disease and stuff. That is a huge incentive. And 

the question is—it does not take 10 years to really develop a drug. 

You can have a breakthrough. You can come up with the chemistry 

of it. The reason that it takes 10 years is the approval process and, 

now, the $2.6 billion is the latest cost. 
28 

Dr. GULFO. It is really about what I said about shifting the 

standard. When the standard is truly safety—we do not want to 

give toxic stuff, right? And, we want to know how you can administer the drug safely. And, effectiveness. Effectiveness should be 

the activity of the drug—the pharmacodynamic activity. The FDA 

has taken that to unrealistic endpoints. They want to see survival 

endpoints. They want to see these endpoints that take tremendous 

trials and tremendously long follow-up. And to me, that is the real 

problem. Again, I could not agree more with Darcy. I wrote an editorial about this. The answer to ‘‘Right to Try’’ is getting drugs approved faster. That is the answer. 

Chairman JOHNSON. So, let me ask, in terms of a company, is 

there any legitimate disincentive, other than having an adverse effect and having the FDA just say, ‘‘OK, this drug is ended,’’—or the 

trial lawyers? I mean, if you are doing a scientific study and you 

are doing a clinical trial and all of a sudden you are starting to provide this drug for people that are not in this very controlled study, 

is there a legitimate scientific concern about harming the results 

of the trial, in terms of the information that you are getting? 

Dr. GULFO. Actually, the answer is that there is no benefit to 

doing it, because I cannot dose enough of these one-off patients to 

get a claim in that. Right? So you need large—to do a study, you 

need a lot of patients. OK? So the companies pick breast cancer or 

they pick prostate cancer—a great example. However, it might be 

a drug that is focused on a particular mutation where the same 

mutation is shared with some childhood cancers. What would be 

great—and I would love to see us get there—is if we are not approving drugs on the basis of cancer type, but we are approving 

drugs on the basis of the genotype of the cancer. And then, they 

could be instantly applied in other places. Then you could do a basket approval. You could bring all sorts of patients, age groups, and 

certain disease types into one trial. FDA is not there yet. 

Chairman JOHNSON. Well, I will turn it over to Senator Ayotte, 

but, first, would it be advantageous for clinical trials, for gathering 

information, and for approving safety and efficacy, if you just had 

more of these drugs available to people who want to use them? Or 

would that actually harm your ability to get information? Do you 

know what I am asking? 

Dr. GULFO. The more that are available, the more that are approved, and the more that are in the hands of the doctors, the more 

discoveries that we get. 

Chairman JOHNSON. OK. 

Dr. GULFO. The more where a doctor observes, ‘‘Wow, when I 

give it to this patient’’—— 

Chairman JOHNSON. That would be my assumption, so OK, good. 

Dr. GULFO. Yes. 

Chairman JOHNSON. Senator Ayotte, if you are ready. 

OPENING STATEMENT OF SENATOR AYOTTE 

Senator AYOTTE. Thank you. I want to thank you, Chairman and 

Ranking Member. And, certainly, thank all of you for being here 

today. Before I left, I got to hear almost all of your testimony, and 

it was very compelling and so important. 
29 

I have had constituents that—there was a young girl who passed 

away from a rare form of cancer, and her family came to me and 

certainly wanted the opportunity for compassionate use through 

the FDA—and really they got the runaround. It was very difficult. 

And, as you think about the difficulty that—all of the other things 

that families are dealing with under those circumstances. 

I know that there has been a lot of discussion today about the 

incredible work that you are doing, Ms. Goodman, trying to help 

families navigate this issue. But, it seems to me that the FDA— 

does anyone have a sense of when the FDA—they put out this draft 

a year ago to make this process more simplified and to make it 

easier for families, because there is such a runaround. And you are 

all so engaged in this. Have you heard anything from the FDA— 

Doctor, I saw you shake your head—about what they are waiting 

for? This is a year. We are talking about families that are struggling and every minute matters to them. And so, it is really troubling to me that they have not issued final guidance. Does anyone 

have a sense—have we heard anything on this? 

Dr. GULFO. I know just what you are talking about. It was an 

effort, to reduce the 100 hours that it takes to put in an application, into a 45-minute process. And we are all waiting with you. It 

is written. I believe that a draft guidance document was written, 

and it has not been implemented. But, I think that Darcy knows 

more about that than I do. 

Ms. OLSEN. I just know who you can talk to at the FDA—who 

is in charge of that. It is Dr. Peter Lurie. They promised over a 

year ago that they were going to make it a 45-minute process, and, 

I think that, for people who work in this field, it is not a big surprise that they have not finished that form. 

But I will say this: Even once that form is finished, it is not 

going to solve all of the problems. It will be a little bit easier, but, 

we attached it to my testimony—just issued an investigational report on the compassionate use process which really goes through 

the disincentives that the companies face and why they do not participate. And that will not change just with a shorter form. That 

is going to require some of the bigger reforms, like they have done 

in Europe. And, of course, reciprocity would be very helpful to get 

drugs here today. 

Senator AYOTTE. I hope—— 

Chairman JOHNSON. Really quick, Senator Ayotte, just so 

you—— 

Senator AYOTTE. Yes, I hope that we can follow up on that. 

Chairman JOHNSON. No, we have already—as part of this hearing, we sent out an oversight letter asking that specific question, 

along with other things. So, we will certainly—as soon as we get 

feedback from the FDA, we will give you the answer. 

Senator AYOTTE. Good. I hope so, because this is really just 

awful. I appreciate what you have said today, and, Ms. Olsen, you 

really put it well. How are we taking this decision-making away 

from families who are in a position where it is a life-or-death situation for them? And what are we trying to protect them from by not 

allowing them to make their own decisions? It is really hard to understand. I understand if it is not a situation where there is a lifeor-death situation, but let us face it, if we all put ourselves in the 
30 

shoes—if we put ourselves in your shoes, Ms. McLinn—it is hard 

to do, but, I know that, as a mother, I would want to fight and do 

everything that I could, and I would not want to leave any stone 

unturned when it came to my son. And, I happen to have an 8- 

year-old, Jacob, by the way, and so I am hoping that we can take 

this issue up in this Committee, because I think that you deserve 

more focus on research—that is critical, and that is something that 

obviously I am very supportive of. We need more focus, though, on 

the things that we know are working—to give you access to—and 

the fact that, Diego, you had to move and your family had to move 

overseas to get drugs that have been available overseas—you are 

right, not every family can do that. But, you should not have to do 

that. 

So, we have to be able to do something about it. Honestly, it is 

common sense and we need the FDA to also start putting themselves in the shoes of the people who they are there to serve. The 

FDA is there to serve all of us. The FDA is there to make sure that 

people can be protected, but not from themselves. It is about letting 

them make decisions. I hope that we can come up with a really 

strong, bipartisan consensus with some of the feedback that you 

have given us today. 

And, I want to thank all of you for coming here. This has been 

incredibly moving, and you have really distilled this down to some 

concrete actions that we can take as Senators that can make a difference. So, we look forward to working with you on all of that, and 

we are so glad that you have come here today. Thank you. 

Chairman JOHNSON. Thank you, Senator Ayotte. Senator Carper. 

Senator CARPER. Given what Senator Ayotte just said, I may 

have missed this, but, while you were out of the room, I have been 

in and out of the room, too. We are trying to do the rest of our 

schedules and be here to listen to the testimony. But, the question 

that I asked—remember, I telegraphed a question. I said that I am 

going to telegraph my pitch. The question that I was going to ask 

was: What do you think that those of us who are sitting over here 

on this side of the dais can do, either through legislation or, maybe, 

through partnering with the Administration, to improve patient access to new treatments or to new therapies? And, if you could just 

briefly address that for me, that will pretty much be it. Do you 

want to go first, Ms. Olsen? 

Ms. OLSEN. Thank you, and I—— 

Senator CARPER. Give us a short to-do list—one thing, maybe, 

one thing. And we will ask everybody to just give us one good idea. 

Ms. OLSEN. OK. Reciprocity, which we talked about, with European countries, and since I prepared for your first question, which 

was 2—— 

Senator CARPER. Go ahead. 

Ms. OLSEN. For these drugs that are being developed for people 

with life-threatening, terminal illnesses, we need provisional access, which means that, as soon as they know that something is 

working, they let people go ahead and put it on the market and 

study it, until it gets the final green light. That will solve the problem of companies not participating. 

Senator CARPER. OK. Thank you. 
31 

Ms. MCLINN. Thank you for asking this question. I wanted to 

come here today and tell you guys exactly what you could do to 

help Jordan—to help my son—and that is all I have thought about 

since I was invited to come here to testify. And, the truth is that 

I do not know and I cannot give you an exact answer, and that is 

really hard for me to say because I am used to problems just having—I am a math teacher. I am used to a problem just having a 

cut-and-dry answer. 

Senator CARPER. My guess is that you are a pretty good teacher. 

Ms. MCLINN. What is that? 

Senator CARPER. My guess is that you are a pretty good teacher. 

Ms. MCLINN. Thank you. But, yesterday, I had the opportunity, 

and I was actually in Speaker Ryan’s office, and I spoke with his 

chief of staff. I told him, ‘‘In 2012, when the President signed 

FDASIA, that had a lot of support.’’ And, I asked him, ‘‘Can you 

get the President of the United States to go to the Advisory Committee (AdCom) meeting and say, ‘Hey, I signed this. The Congress 

said that we want you to do this. Can you do this?’ ’’ And I know 

that that is an outlandish request, but you asked what you can do. 

So, I would like to see a physical presence by Congress at an 

AdCom meeting, or with the FDA. I would like to see you speak 

with them, directly, and say, ‘‘We want you to use the tools that 

we have already given you. This is legislation that already exists.’’ 

And, I want someone from Congress to stand up and say, ‘‘Will you 

please do this?’’ 

Senator CARPER. All right. Good. Thank you. 

Diego, before you speak, let me just say that we have a lot of witnesses before this panel. You are one of the youngest, and I want 

to say that you are one of the best. You did a great job. 

Mr. MORRIS. Thank you. 

Senator CARPER. Would you like to answer my question, please? 

Give us some good advice, please, before we adjourn. 

Mr. MORRIS. I think that the compassionate use process needs to 

be expedited. Particularly, when I was going through treatment, 

the drug that I had in London needed to be taken while I was 

doing the chemotherapy. And, the compassionate use program 

would have taken far too long, so we did not even apply because 

we were advised that it would take too long. The process needs to 

be expedited, because, in some cases, it needs to be faster. 

Senator CARPER. All right. Thank you, Diego. Dr. Gulfo. 

Dr. GULFO. Yes, three things, I think, and I appreciate the question. 

Senator CARPER. Sure. 

Dr. GULFO. First, I think that the FDA has to feel loved. We all 

need to love the FDA, and not do fire-alarm, knee-jerk oversight, 

if you will, when things do not go well. So, I think that that does, 

as I wrote in my—— 

Senator CARPER. I call those ‘‘gotcha’’ hearings. 

Dr. GULFO. Yes, OK. And so, even when the FDA gets it right— 

look at the case of Avandia. They still get beaten up for it, and that 

is just wrong. 

Senator CARPER. That is a good point. 

Dr. GULFO. And, that makes them retrench, and it is terrible. 
32 

That, combined with really letting them know that we want 

them to promote health, OK? Sure, protecting is a part of promoting, but we want them to promote health. We do not expect 

them to guarantee absolute safety for all patients and all drugs. 

And, then, my third wish would be to get the FDA back to focusing on safety and effectiveness—not on these other outcomes. 

Now, in my written testimony, I have a proposal for that. You 

can have four categories of the nature of the evidence, and one of 

the categories could be those longer-term outcomes. Fine with me. 

But, I think that if you get the FDA back to promoting and focusing on safety and effectiveness, and not getting the heck beat out 

of them when things go wrong—because things do go wrong—I 

think that we could do a lot. 

Senator CARPER. Great. That is great advice, thank you. 

And, Nancy, one more, please? 

Ms. GOODMAN. Thank you, Senator Carper. 

The first solution, again, is that we need to reauthorize the Creating Hope Act, so that companies have incentives to develop pediatric rare disease drugs, and I hope that the Senate will move on 

that. 

Second, when companies are developing drugs for adults, we 

need to give companies incentives and requirements for them to 

just test them in kids, and update the Pediatric Research Equity 

Act, so that it protects children with cancer. 

And, maybe, we would ask companies to explain why they have 

minimum ages—a minimum age of eligibility for their adult trials 

at 18. Maybe, ask them to explain whether there are medical and 

scientific rationales for not lowering it, so that kids with terminal 

illnesses can get access to these drugs. 

And, finally, it is only a partial solution, but it is a very important one. I think that it would be terrific if Congress could pass the 

Andrea Sloan CURE Act to start improving the compassionate use 

process. 

Thank you. 

Senator CARPER. OK. Thank you. 

Mr. Chairman, Cole, I am going to ask you to come over here just 

for a second. For a number of years, a young man from Delaware 

named Cole Hamstead has come to Washington. He brings his 

Mom with him every time. Laura and Cole have been a vital part 

of the work of the National Hemophilia Foundation (NHF). He is 

10 years old and a wonderful young man. And, I showed a picture 

to your son, to Jordan over here, of Cole 3 years ago with me and 

explained to Jordan that, in that picture, Cole was then just the 

same age that Jordan is today. In response, Jordan was nice 

enough to offer to let Cole play with his toys as sort of a sign of 

welcome. 

Ms. MCLINN. Good job, buddy. 

Senator CARPER. These are two brave young men, courageous 

young men, who face adversity in their lives and have found, 

through the help, love, and support of a lot of other people, some 

good. And, I just want to say, to those of you who continue to lead 

a good fight—and to those who have taken adversity, Nancy, in the 

loss of your own son—to make sure that good things happen for a 
33 

lot of other young people in our country, thank you. You are doing 

the Lord’s work. God bless you. 

Ms. GOODMAN. Thank you. 

Senator CARPER. Thank you. 

Chairman JOHNSON. Thank you, Senator Carper. 

Again, I want to just thank all of the witnesses. I think that this 

has been a wonderful hearing—powerful testimony. I appreciate 

your taking the time and answering our questions. 

I am going to—I think, with consent—we are going to have an 

honorary Chairman close out the hearing. So, I am going to switch 

chairs. I wish that I had a little bit of a fancier sign. And, I have 

a couple of things to say. I am going to switch chairs here, and 

then we will let you gavel it out. 

Senator CARPER. Mr. Chairman. 

Chairman JOHNSON. I have to say a few magic words here. 

This hearing record will remain open for 15 days until March 11, 

at 5 p.m. for the submission of statements and questions for the 

record. 

This hearing is adjourned. 

[Jordan McLinn bangs gavel.] 

Chairman JOHNSON. There we go. Thank you. 

[Applause.] 

[Whereupon, at 11:43 a.m., the Committee was adjourned.] 

(35) 

A P P E N D I X 
36 

Finally, we recently learned our friend and colleague Claire McCaskill was diagnosed with 

breast cancer. Fortunately her prognosis is good and she is in good spirits. I know the thoughts 

and prayers of this committee are with her. 

Thank you all for being here today. I look forward to your testimony. 
37 

Statement of Ranking Member Torn Carper 

"Connecting Patients to New and Potential Life Saving Treatments" 

Thursday, February 25,2016 

As prepared/in· de/irery: 

Thank you, Mr. Chairman, for calling this hearing today. I appreciate your willingness to open a 

conversation about this issue that I know is a very critical one to Americans seeking access to 

potentially lifesaving treatments and new medical innovations lor themselves or members of 

their family. 

I also want to thank our witnesses, especially Ms. Laura McLinn, Mr. Diego MatTis, and Ms. 

Nancy Goodman, for their thoughtful and insightful testimony, and especially for their 

willingness to share their personal stories with us. 

Today, we will hear from patients. their loved ones, and others on potential opportunities to 

improve access to medical breakthroughs and life-saving medical treatments. These individuals 

and their families have faced some of the most difticult and challenging circumstances and 

decisions anyone could face. They deserve our compassion and our understanding. 

Speaking as a father, husband, brother. and son, it's important that we learn from our witnesses 

experiences so that we in Congress can work together with the Executive Branch, patient groups, 

industry. and other stakeholders to ensure that all Americans can gain access to safe and etTectivc 

lifesaving treatments as quickly as possible. 

Simply put, the development of new medicines is a long, complex, and risky process. For 

individuals with lite-threatening conditions and their loved ones, safe and ciTective treatments 

cannot come quickly enough. 

As we will hear t!·om some of our witnesses today, the path f'or patients and their physicians to 

access innovative new treatments may not be clear. Reforms may be needed to make sure that 

patients and their families and doctors have the information they need to explore potential new 

treatment options. 

The U.S. Food and Drug Administration (FDA), which is charged with ensuring that the drugs 

available to American consumers are sate and eflective, has given an extraordinary level of 

attention to the requests of patients with life-threatening conditions. In fact, they've approved 

more than 99 percent of requests for emergency treatments. 

Despite these high approval rates, I understand that the FDA believes more can be done and is 

continuing to work to improve patient access to these experimental medical treatments. 

I hope we can help with those efforts and continue to work closely with patients, health care 

providers, the pharmaceutical industry, and the FDA to ensure that all patients and their families 

can access safe and reliable treatments as quickly as possible. 
38 

I want to close by thanking the witnesses and their families again for their willingness to share 

their stories and put forward possible solutions to these challenging issues. 
39 

Testimony of Darcy Olsen 

President 

Goldwater Institute 

Phoenix, Arizona 

Before the 

United States Senate 

Committee on Homeland Security and Governmental Affairs 

"Connecting Patients to New and Potential Life Saving Treatments" 

February 25,2016 
40 

Chairman Johnson, Ranking Member Carper, other Members of the Committee, thank you: 

As l was preparing my testimony for you on Monday, I received a call from an old friend 

of mine. "Oh Hazel! How are you?" ·'Not good,'' she said, "l was just diagnosed with ALS." 

Only weeks after the diagnosis, her deterioration has been so rapid that she can no longer 

dress herself. She has already met with Hospice. After all, her physicians told her, ''There really 

are no treatments for ALS.'' But what Hazel's doctors really mean is that there arc no FDAapproved treatments available. The cruel truth is that there are a dozen treatments in the FDA's 

pipeline to treat ALS right now. 

In my book, The Rir;hrro Trv, l tell the story of a man named Ted Harada. 1 We call Ted 

"Lazarus," because he is the first known survivor of ALS. No one would call an ALS diagnosis 

lucky, but Ted was fortunate to get into a clinical trial where he received a treatment that 

reversed his ALS symptoms. Today, seven years after his diagnosis, he swims with his kids and 

completes 5k races. He's shown no decline in his respiratory ability at all. Ted is one of32 

Americans who were lucky enough to try this cutting-edge therapy. But in the years since the 

clinical trial began, 24,000 people in the United States have died from ALS. 

Why should only 32 Americans with ALS have a chance to try to save their lives? And 

what about the millions of Americans with other terminal illnesses? Why arc so many people 

dying when promising treatments exist~ 

1 Olsen, Darcy. The Rir;ht to 1/y: How the Federal Government Prevents Americansfi·om 

Gelling the Lifesaving Treatments They Need (New York: HarperCollins, 20 15), 1-19. 

2 
41 

The problem is the FDA has a very archaic process for approving treatments, especially 

for people with life-threatening diseases. It takes an average of 15 years to bring a new drug to 

market.2 

What does 15 years mean? 

80 percent of oncologists and neurologists say the FDA's lengthy process has hurt their 

ability to treat their patients with the best possible care. 3 During the course of writing my book, 

the mother of two boys with DMD said to me. ·'By the time this drug is on the market, we are 

going ro lose an enrire generation r!f'boys.·· 

It is unethical not to give those boys a chance at life. 

The right to try to save your own life is the most personal right we have. It is unethical 

and unconstitutional for government to deny patients that right. In America today, terminal 

patients have the right to hasten their deaths through Right to Die laws, but they do not have the 

right to try to fight to live. You can get drugs to end your life but not to save it. I think most of us 

would agree there's something desperately wrong with that. 

That's why the Goldwater Institute designed what we call Right to Try laws. As of today, 

24 states, including 7 of the home states that Members of this panel represent, have adopted the 

Right to Try. Under these laws. if you have a terminal diagnosis and the FDA-approved 

treatments aren't working f(lr you, you have the right to try to save your life by taking 

2 Biophannaccutical Research Industry, 2015 Profile, https://s3.amazonaws.com/goldwatermedia!pdt/PDF+8+PhRMA+page2.pdf. Executive Office of the President, President's Council of 

Advisors on Science and Technology, Report to the President on Propelling Innovation in 

Drug Discovery, Development, and Evaluarion (Sept. 20 12), 

https ://s3 ,amazon a ws.com/ go ldwater-mcdia/pd t/PD F4 W h ite+H ouscpagc3 8%23 7. pd I. 

3 Olsen, 771e Right to Try, 187. 

3 
42 

investigational medicines that are under study at the FDA but may still be ten years away from a 

green light. 4 

We designed Right to Try laws conservatively. Patients must have a terminal illness. 

Their doctor must support this choice and determine that no other government-approved 

options are available. The treatment must have passed Phase I of the FDA clinical trial process 

and remain in the clinical trial process. These laws simply extend to terminal patients who are 

out of time and options the same permission to use investigational treatments as those who are 

fortunate enough to be enrolled in clinical trials. 5 

Right to Try laws will not help every patient in need, but they are a powerful step in the 

right direction. We know that people arc being treated under the laws at this time and that lives 

are being saved thanks to those treatments. 

In addition to state Right to Try laws. there are two key reforms that Congress should 

adopt this year to connect patients to new and potentially life-saving treatments. 

First, federal law should allow doctors to prescribe- and manufacturers to sell- drugs to 

terminal patients after they have passed Phase I safety testing on a provisional basis. Terminal 

patients don't have time to wait 12 or 15 years for efficacy testing. This would put treatments 

and medicines, like those that saved Ted Harada's life. in the hands of dying patients today. 

Provisional approval would also allow data to be collected on both the benefits and risks of a 

4 In just two years, Right to Try has passed in 24 states, often near unanimously and with 

bipartisan support The current Right to Try states are: Alabama. Arizona, Arkansas. Colorado. 

Florida. Illinois, Indiana. Louisiana, Michigan, Minnesota, Mississippi, Missouri, Montana, 

Nevada, Notih Carolina, Notih Dakota, Oklahoma, Oregon, South Dakota, Tennessee, Texas, 

Utah, Virginia, and Wyoming. 

5 Right to Try Model Legislation. 

http://scienceblogs.com/insolence/files/20 14/l 0/GoldwaterlnstituteRightto TrvModcl.pdf. 

4 
43 

new drug in the actual full patient population rather than a tiny subset available to a select few in 

clinical trials. 

Second, Congress should allow for reciprocal approval of treatments approved in 

advanced nations. An estimated 30 percent of the newest advances in medicine are first available 

overseas. Drugs that have already received the green light in countries such as Germany and 

Japan, for example, should be made available to patients here in the U.S. 6 This would bring 

countless proven, life-saving treatments to patients in America now. 

The main concern I heard in writing The Right to Try was that some treatments could be 

dangerous. But as Ted puts it, "ALS is I 00% fatal. It"s not a big risk for a guy with a fatal 

disease." 

lfyou were on a sinking ship. would you pass on the only available lifeboat because the 

government hadn't certified it yet? No, you'd say, "Put the lifeboat in the water!" 

As a society, we can and should debate the best ways to make better, stronger lifeboats. 

We can and should figure out the best ways to pay for lifeboats and make sure we have more of 

them. But there is no argument for withholding the lifeboats we do have from drowning kids. 

We should all keep in mind the people. like my friend Hazel, who are facing their last 

day as we debate these issues. They don't have time to wait. 

Let's get the lifeboats in the water. 

Respectfully submitted, 

6 For an example of a bill that would permit reciprocity, seeS 2388, "Reciprocity Ensures 

Streamlined Use of Lifesaving Treatments Act of2015," https://www.congress.gov/bill/114thcongress/senate-bi 11/23 8 8/tcxt. 

5 
44 

Darcy Olsen 

President 

Goldwater Institute 

500 E. Coronado Rd. 

Phoenix, Arizona 85004 

www.Goldwaterinstitute.or!! 

6 
45 

APPENDIX: INVESTIGATIVE REPORT 

DEAD ON ARRIVAL: Federal "compassionate usc" leaves little hope for dying patients 

By Mark Flatten 

You are dying and have no hope. 

Your disease is 100 percent fatal. It's only a short time before it kills you. 

There are no treatments that have been approved by the federal Food and Drug Administration. 

There is a new therapy that could save your life. But it is still being tested in people who have the same 

disease in rigidly controlled studies called clinical trials that you are too sick to qualify for. 

It will be a decade or more before the new drug is available to your doctor. You will be long dead by then 

What are you willing to do. and how much risk are you prepared to take to try to save your life? 

Those are questions thousands of Americans face every year after being diagnosed with a deadly disease 

for which there is no cure. at least none that has been approved by the FDA. 

For them. their only chance at survival will be to get access to an innovative new drug before it's too late. 

It may be a faint hope. or even a false one. But it is their only hope. 

The FDA's compassionate usc program is supposed to be that one last chance. 

Formally known as expanded access, compassionate use is meant as a way to treat dying patients with 

medications that are still being tested in clinical trials and are therefore not otherwise available. 

Compassionate use must be requested by the patient's doctor. endorsed by the company that makes the 

drug, and approved by officials at the FDA. 

But an investigation by the Goldwater Institute shows that the entire system for gaining access to an 

unapproved medication is so rigged with bureaucracy and disincentives that it is bound to fail in most 

cases. Critics say it was designed that way, ensuring that only a tiny number of patients are able to 

navigate the complex, costly. and time-consuming maze that must be cleared just to file a compassionate 

use application tor the FDA to consider. 
46 

The problem with the current system is not just that it takes doctors I 00 hours or more to complete the 

application process for FDA approval. 

Or that clinical trials take too long and cost too much. 

Or that new cures for deadly diseases like cancer are typically being developed by cash-strapped small 

companies that risk financial ruin if they grant early access to their products to save the lives of dying 

patients. 

It's the way all of those things interconnect into an unworkable system that strips dying patients oftheir 

tina! option to save their own lives. 

It is a system of all risks and no rewards. 

And the lynchpin that binds it all together is the regulatory scheme created by the FDA. 

To sell a new drug in the United States, and make any money off of it pharmaceutical developers must 

get the FDA to certify that it is safe for use in humans and etTective in treating the targeted condition. 

The only way to prove that is thro,u;h clinical trials: slow. tightly controlled, carefully monitored tests 

that normally consist of three phases in which the therapy is given to a select group of patients to gauge 

its effects. 

With everything riding on those trials. drug companies rarely do anything that could raise their risk of 

failure, or draw the ire of the FDA. That especially includes giving their treatment to a dying patient, 

whose death could be counted against the company seeking approval. 

Those facing imminent death cannot access a Q.mg while it is being tested, even if early results show that 

it works better than existing treatments, unless they are among the fortunate few who qualify for clinical 

trials. That amounts to a death sentence for most patients, even though their cure may have already been 

found. 

lt takes an average of I 0-15 years for a new drug to get through testing and be approved by the FDA for 

sale to doctors and patients, according to g_o~~~]lment and industrv estimates. 

Most fail. 

2 
47 

Drug companies spend an average of$1.4 billion to get a product approved by the FDA. The cost of 

bringing revolutionary new treatments to market can reach $5 billion. Virtually all of those costs must be 

paid by drug companies before they can sell their first dose. 

The trials are all or nothing. failure at any stage usually means the product is dead. 

Small drug companies developing innovative treatments are normally a collection of scientists and 

businesspeople who lind a new way to treat a disease and set about raising money from private investors 

to pay for the early stages of clinical trials, usually through the sale of stock or equities. 

Once the product reaches later stages of testing and shows promise, the inventors typically sell it to a 

large drug company, either outright or through some type of licensing arrangement, according to industrj/ 

experts and company records. That business plan evolved because few start-up drug developers will ever 

be able to raise the billions of dollars required to take a product through all phases of clinical testing. 

especially since they won't make any money from the drug until after the FDA approves it. 

Only big pharmaceutical companies have that kind of money, start: and regulatory expertise. 

for the small innovators. making their drugs available to a dying patient through compassionate use is 

risky. 

They often don't have the staff to deal with patients or the money to provide their products through 

compassionate use. 

Their primary selling point to investors is that their drug shows promise in clinical trials that are 

proceeding smoothly. Any deviation is enough to send investors fleeing and potentially ruin tl1e company. 

Drug developers get no direct benefit from compassionate use. 

They do not get government funding. and are rarely paid for making their products available. 

Even if the patient does well and makes a miraculous recovery, that does nothing to help the product in 

formal clinical trials, 

If something goes wrong, it is counted against the drug by the FDA. 

3 
48 

All serious reactions or patient deaths, called "adverse events," must be reported to the FDA. The agency 

can, and has, suspended clinical trials because patients receiving treatment through compassionate use 

have died. 

The FDA maintains that such suspensions are rare, but it is a widespread fear in the drug industry. 

There also is the chance that a bad outcome will cause investors to question a drug's value and abandon 

the company's stock, leaving it with no way to raise the money necessary to continue testing. 

LOADED WITH DISINCENTIVES 

In short. the entire regulatory and financial structure of the drug industry is so loaded with disincentives 

that treatment under compassionate use is rare by design. 

"The whole system is built to be completely nonfunctional. It's a system that just is so fraught with 

barriers and disincentives and reasons not to do it," said Steve Walker of the Abigail Alliance, a patient 

advocacy group. ''Our entire system is set up. including with very unchallengeable eniorcement authority 

by the FDA, to prevent people from gaining access to a drug of any kind that has not yet been approved 

by the FDA.'' 

The Goldwater Institute has spearheaded the adoption of state Right to Try laws, which allow doctors and 

drug companies to proceed without FDA approval in providing treatment to dying patients who have no 

other options. Those laws have passed in 24 states with overwhelming bipartisan supp011 and almost no 

opposition. 

Critics of Right to Try say it is not needed, that compassionate use under FDA rules is the appropriate 

mechanism for dying patients to get the treatment they need. Drug companies are unlikely to risk the 

wrath of the FDA by providing their products to patients based on state laws alone. so the laws will not 

lead to widespread access to investigational medications, they argue. 

But even critics concede that Right to Try laws have raised public and political pressure on the FDA to 

change its system for allowing those with no other options to seck treatment with investigational drugs. 

4 
49 

That includes Dr. Arthur Caplan. director of the division of medical ethics at the New York University 

Langone Medical Center. 

"'Right to Try. as much as I fume and fuss about it, has brought the issue forward,"' he said. "It has pushed 

the issue to the forefront. Congress must pay attention. Ethicists must pay attention; companies. media. 

Even if I think the laws are not going to get us far in getting drugs to people, I think it put the issue front 

and center.'' 

'SUCCESSFUL PROGRAM' 

FDA officials and their defenders insist the current system works well, and the agency is not an 

impediment to terminal patients getting the care they need. Their primary talking point is that the 

FDA approves 99.5 percent of the applications it receives for compassionate use. 

Since 2010, the FDA has approved an average of about 1,200 applications for compassionate use per 

year. In 2015, it approved l£56 applicat[sw;; and rejected six. 

"'I would say it's a very successful program. The agency has an extremely good track record:' Richard 

Klein. director of the FDA's patient liaison program, said at a recent conference about expanded access. 

But critics say the FDA's numbers are meaningless. 

All they show is the total number of formal applications that were approved and rejected by the FDA. 

They do not show the number of requests that were squelched because of agency regulations before they 

were ever filed. 

The FDA does not track those numbers. 

No one knows how many requests for compassionate use drug companies receive or reject. They are !LoJ 

required to keep or report that information. One indication is that the number of ongoing clinical trials 

open to compassionate use is a tiny fraction. far Jess than I percent, according to the government-run 

website cl inicalttj1!]~,gg"y. 

Drug companies eannQ! be compelled to approve a compassionate use request. If a company refuses to 

provide the drug, the application cannot be forwarded to the FDA. 

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50 

When Rep. Mike McCaul, R-Texas, was crafting a bill in 2014 aimed at simplifying the compassionate 

use process, he initially wanted language that would require drug companies to confidentially disclose 

that information to the Government Accountability Office. The idea was to allow the GAO to compile 

overall industry data on the number of requests made to companies, how many were approved and 

rejected, and the reasons why. 

Drug industry lobbyists considered that provision a deal killer, and it was stripped from the bill that 

McCaul later introduced. 

Beyond that, there is no way to know how many doctors simply refuse to make compassionate use 

requests for individual patients because of the long. cumbersome, and costly process required by the 

FDA. 

"If you have to deliver the application at the top level of Mount Everest, they will approve it.'' said Garo 

Annen, chief executive officer ofAgenus Inc .. a small biopharmaceutical company developing 

immunotherapies to help treat cancer and other diseases. ·'The FDA will do the approval process, but 

everything that needs to be put into place, which is an FDA requirement. makes the process very 

onerous.~· 

The best evidence against the FDA's claim that it is not an impediment to compassionate use is the 

numbers themselves, said Carla Mann Woods. formerly a medical device industry executive. and now a 

board member of the Alfred E. Mann Institute for Biomedical Engineering at the University of Southern 

California. 

About 600,000 people die annually of ca]l.£CJ: alone. Add to that the millions of people facing other lifethreatening or debilitating diseases, and the 1.200 compassionate use applications approved by the FDA 

annually is shown to be a paltrv f).gure, Woods said. 

"In this era of both scientific revolution and information where anyone can find anything on the Internet. 

ask yourself this: Can you actually believe that only I ,200 dying Americans want to live badly enough to 

find a legitimately applicable, unapproved therapy and ask to get itT she said. 

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51 

TOO MUCH TO BEAR 

Nick Auden does not exist in the FDA's statistics. 

No drug company would allow its product to be used to save him, so no f(mnal application ever reached 

the FDA to approve or reject. 

Auden, a 41-ycar-old father of three, died in November 2013. 

The Australian lawyer and corporate executive was living in Denver when the first sign surfaced of 

melanoma, a type of skin cancer. 

In October 20 I L Auden felt a lump under his arm. When he had it checked, his doctors told him he had 

late-stage melanoma that had spread to his spine, arm, and leg. 

Doctors gave him a I 0 percent chance of survival, considering the treatments available at the time. Most 

patients in his condition lasted six to nine months. 

Auden tried the FDA-approved treatments, undergoing intensive immunotherapy that seemed to work at 

first. But then the cancer returned, and his doctors suggested clinical trials. Auden seemed like a perfect 

candidate. He maintained an active lifestyle and. aside from the cancer, remained physically strong and 

emotionally upbeat. 

Auden managed to get into one trial using a new drug that targets a type o_f genetic muta!iQD linked to 

about half of melanoma patients. It worked for several months, but then the tumors started growing again. 

That was enough to get him kicked off the trial. 

Auden·s doctors were familiar with a new line of drugs being developed. known as anti-PD I therapies, 

which allow the body's immune system to target and attack cancerous cells. 

Merck and Bristol-Myers Squibb were testing versions of anti-PD I drugs in clinical trials. 

It seemed Auden's miracle cure may have been found. His doctors scrambled to get him into one ofthe 

trials. 

Then came the complications. 

Auden developed a brain tumor, which disqualified him from trials. 

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52 

The tumor was treated with a type of radiation surgery, but by the time he was eligible to qualify for a 

clinical trial a second tumor appeared. which again was treated with the same procedure. 

In July 2013. Auden's brain tumors were considered stable, and he was tinally accepted into a Merck 

trial. By then he had spent almost seven months trying to qualify for the testing-about the same amount 

of time he was initially told most patients like him could expect to live. 

As Auden was preparing to fiy to Los Angeles to begin treatment, he experienced a partial bowel 

obstruction, which got him disqualified from yet another round of clinical trials. 

Auden's doctors told him his last option was compassionate use. 

His past business connections gave him contacts inside Merck. He and his wife, Amy. tried working those 

contacts to get the company to approve their application for compassionate usc. Their efforts were 

rejected, and the contacts told them to stop calling. 

Merck officials said the company only made enough of its drug for people in clinical trials. It was not 

available to anyone through compassionate use. 

Auden was told his only option was to enroll in a clinical trial. When he responded he'd tried that, and 

been rejected, he was told there was nothing more the company could do. 

Dealing with Bristol-Myers was even more tl·ustrating, Amy Auden said. 

Officials there refused to even discuss compassionate use, saying only that its drug was too unsafe to use 

outside of clinical trials. 

WALL STREET WATCHING 

What investors were hearing was much different. 

Researchers touted the new line ofanti-PD I drugs at a meeting of the American Society of Clinical 

Oncology in mid-20 13 as showing unprecedented safety and success in treating melanoma and other 

types of cancer. 

Wall Street took notice. with the price of Bristol-Myers and Merck shares increasing more than 3 percent 

in a single day following the oncology conference, the New York Times wrote in an extensive article about 

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53 

the new miracle cure in June 2013. Billions of dollars in potential sales were at stake for the company that 

got its drug approved by the FDA first. 

That was pa1iicularly galling, Amy Auden said. 

·'The word unsafe made me so angry because their share price increased when they announced this 

breakthrough drug at the conference," she said. "You can't say to someone who's got a death sentence 

that there is no hope for you, even though we've got this drug that we're talking on the television about 

and it's a breakthrough. That doesn't wash." 

After getting the runaround from both Merck and Bristol-Myers, the Audens took their story public, doing 

media interviews and launching a social media campaign called ",2.<.LYe ... Lockv's Dad," named after their 

oldest son, Lachlan, which gathered more than a halt~million signatures in support. 

Both companies refused to back down, even after Auden got assurance from the FDA that there were no 

safety concerns and their application for compassionate use could be approved within 24 hours once a 

drug manufacturer agreed to provide the medication. 

By November, his health was starting to deteriorate. In a last-ditch attempt to save his life, Auden flew to 

Houston to receive a ditTcrent kind of therapy unrelated to the anti-PD I drugs. 

While in Houston, he had a massive seizure and was unable to tolerate further treatments. 

He and Amy flew back to Denver to spend his tina! days with their children, and he died soon after. 

Less than four months after Auden's death, Merck announced it would make its anti-PD I drug 

available to dving patien§ through expanded access. 

The Merck version. now called Kevtruda, and the Bristol-Myers version, Opdivo, were both approved to 

treat melanoma patients in late 2014, about a year after Auden died. 

The system failed Nick Auden. said Amy, who lives in Australia, where she is raising their three children, 

now ages three, seven, and I 0. 

"It beggars belief that people still have to deal with the illness and then tight to get the drug too, which is 

proven safe," she said. "Unless you are going through something like this, you don't know what the 

system is. But the system was so frustrating that I can't believe it was allowed to exist like this. 

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54 

To not get the benefit of that given that it was available in Nick's lifetime. was just too much to really 

bear." 

JUDGMENT CALL 

Just asking for compassionate use is a logistical nightmare. 

Dying patients must first convince their doctors to make the application. Patients cannot petition the FDA 

directly. 

To qualify, the patient must have a condition that is immediately life-threatening or serious. To be 

considered immediately life-threatening, a disease must be at such a stage that there is a reasonable 

likelihood of death within months. or in which premature death is likely without early treatment. 

What counts as "serious" is a judgment call by the FDA. Federal regulations say a serious condition is 

one that substantially affects day-to-day functioning. and includes such factors as whether it is likely to 

cause death and whether the disease is likely to progress without treatment. 

Also, a patient must have exhausted all traditional FDA-approved treatments for a deadly disease like 

cancer. That means those seeking compassionate use tend to be in the later stages of their illness. wracked 

by complications such as weakened organs or immune systems. and often taking other medications to 

cope with pain and debilitation. Those facts alone are enough to prevent most such patients from 

qualifying for clinical trials of investigational treatments. By definition, they also face the highest risk of 

dying and are least likely to respond to last-ditch treatment. 

LOGISTICAL NIGHTMAIU: 

For doctors and patients, the first hurdle is just knowing that a medication exists and finding out whether 

the company that makes it might be willing to authorize its usc. 

Most drug companies do not have policies on compassionate use, or at least do not make them easily 

accessible. A review of more than I 00 companies developing multiple potential cancer treatments shows 

that fewer than 20 had compassionate use policies clearlv posted on their websites. That number includes 

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55 

companies whose websites say their medicines are only available through clinical trials. Those that did 

post compassionate use policies tended to be the largest companies. not the smaller ones which arc 

developing most of the innovative treatments that might offer the best new hope for those near death. 

The doctor must agree that there are no other viable treatments available, and that the risks of 

administering the unapproved medication are outweighed by the risks of the disease. 

Just to fill out the FDA's application form, doctors who think a drug undergoing clinical trials can save 

their patient must commit to spending I 00 hours or more compiling extensive information about the 

patient and technical data on the drug, which may be proprietary information they have no way of 

knowing. They need to write trcatm_e_llU:!nQJllOnitoring plal}!e that are acceptable to both the FDA and the 

drug manufacturer. which become part of the application. 

All of that goes into the 100-hour estimate. 

In February 2015, the FDA published proposed guidance in the Federal Re~ister to begin allowing a new, 

shorter form to be used by doctors to apply for compassionate use. If approved, it will shave about seven 

hours off the time it takes to till out the agency's paperwork, according to the notice. 

If the application for compassionate use is ultimately approved, the doctor will have to abide by whatever 

dispensing and monitoring requirements are imposed hy the company. which is unlikely to make its 

product available without such restrictions. Those requirements typically mirror the protocols for the 

ongoing clinical trials to minimize unpredictable incidents and reactions. 

Both the company and the FDA will also require that data be kept and reported on the patient's medical 

condition, progress, and reactions. That usually means extensive and expensive medical tests that are 

rarely paid for, since most insurance companies do not cover experimental treatments. 

In short, a doctor who agrees to sponsor an application is essentially responsible for designing, running. 

and usually paying for. a miniature clinical trial for a single patient. 

The next step is to get approval by the lnsti1Ll!iQ[Iaj__R£yje_w_floar9. at the hospital or medical clinic where 

the patient will be treated. IRBs are internal panels that weigh the ethical considerations of treating people 

II 
56 

with medicines that have not been approved by the FDA. They usually meet infrequently, adding weeks 

to the approval process. 

Beyond that. applications normally must be approved by the hospital or clinic's lawyers and business 

executives. or board of directors. Though not required by the FDA. those steps are necessary to ensure 

that treating the patient will not expose the institution to lawsuits or prohibitive uncompensated treatment 

costs. according to doctors and drug industry executives who have been involved in compassionate use 

cases. 

TRIAGE 

"Of course there is triage," said Raze lie Kurzrock, director of clinical trials and the Center for 

Personalized Cancer Therapy at the Moores Cancer Center at the University of California. San Diego. 

"The number of patients that we would give compassionate use drugs to would probably be much, much 

higher if the bar for compassionate use was not so high." 

Kurzrock set up and ran early-stage clinical trials at the MD Anderson Cancer Center in Houston from 

2004 until 2012, eventually building it into the largest such program in the country before she left. 

About 1.300 patients went through the trials in her department every year. Kurzrock said her unit only 

tried to get compassionate use for about one patient annually because of the time and runaround involved 

in preparing the application. 

Even before stm1ing the process of assembling the data and lilling out the form, Kurzrock spent hours on 

the phone calling the FDA and drug companies to lind out if there was even a chance that the request 

would be approved. In most cases, the answer was no. 

"So you never get to the point where you put in an application." she said. "It's almost a self-fullilling 

prophecy for the FDA to say they approve everything. because you don't even put in the application 

before you sort of get a verbal approval from the FDA that it's worth doing." 

Even with her level of expertise, assembling the information and lilling out the FDA form would take 

about 50 hours. including the lirst round of phone calls and other research needed to lind out ifthere was 

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57 

any point in seeking approval. Kurzrock said. For a front-line physician, the I 00-hour estimate could even 

be low. 

''The fact that we did maybe one a year in our department, which was the largest of its type, probably in 

the world, I think says it all," she said. "There's only two possibilities: that there was only one patient per 

year that needed compassionate use. and that's really laughable. Or that there were so many barriers that 

even at one of the best places in the world and one of the largest departments that did this as their day in 

and day out job. it was still very challenging." 

The FDA disputes that it takes 100 hours to fill out the application, even though that number appears Q1l 

!ll"-fou.!JA.se!f. The paperwork the FDA uses to apply for compassionate use was designed for a drug 

company applying to run clinical trials. not for individual physicians wanting to treat a single patient. 

Many of the fields in the existing form do not have to be filled out by doctors applying for compassionate 

use, according to Klein of the FDA. The new form, once it receives final approval, will limit the 

application to the eight appropriate fields. 

There is nothing on the form or in the agency's instructions directing doctors to ignore the fields that are 

not required. Klein did not explain why it took so long to make that clarification by developing a new 

form, or when doctors can begin using it. given a year has passed since it was proposed. 

ROADBLOCKS 

If the doctor and hospital agree to take on the task of applying for compassionate use, the patient faces the 

biggest roadblock of all: getting approval from the drug company. 

Drug makers cannot be forced to make their products available for compassionate use. If they refuse to 

participate, the application cannot proceed. 

While no one knows how manv requests they receive and reject. there are indications the numbers are 

high. 

A single company had more than I 00 applications in September 2015 alone, according to its former chief 

executive officer. 

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58 

For drug makers, participating in compassionate use is risky business, regulatory and tinancial experts 

told the Goldwater Institute. 

Drug makers can charge patients the actual cost of manufacturing their products. But they seldom do 

because they do not want to disclose their actual costs and potential profit margin in the event that the 

drug is ultimately approved. So when a company does make its product available to dying patients, it 

almost always provides it for free. 

That can be a major expense. Many new treatments make use of expensive compounds or genetic 

therapies. 

In the early stages of clinical trials, QHLi'csmilLL<J.uantities of an experimental new drug are manufactured 

to keep costs down. That raises fears that making the medicine available in compassionate use cases could 

mean there is not enough to use in clinical trials. 

About the only upside for companies under the current system is the good publicity that can result if a 

patient survives against all odds. However, even that must be balanced against the risk of bad publicity if 

an already hopeless patient dies, even if it had nothing to do with the drug. 

BAD OUTCOMES 

But the biggest fear in the industry is that bad outcomes in compassionate use cases can derail or delav 

the all-or-nothing clinical trials that o11en will determine whether the company itself lives or dies. 

Good news doesn't help. 

If a patient does well and begins to recover, that information does nothing to help the drug company get 

its product through clinical trials. Since compassionate usc patients do not meet the statistically controlled 

requirements of those in clinical trials, positive results are not deemed statistically signiticant. 

[lad news, however, does count in weighing the product's risks. 

All major adverse events, especially the death of an already dying patient, must be reported to the drug 

company and the FDA if they occur in a compassionate use case. 

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59 

That could prompt the agency to halt the clinical trials. It could also require the drug manufacturer to post 

additional warnings on the product's instructions. known as its label. if it is eventually approved and 

marketed. 

Agency officials have long insisted that they understand that compassionate use patients are already near 

death when treatments are administered. and that it would be unfair to count adverse events against the 

drug's clinical trials. However. the FDA has no formal. written policy promising not to hold such 

incidents against companies. 

Then in November 2014, a company called CytRx was participating in compassionate use on an 

advanced-stage cancer patient who died. The FDA put a partial hold on the clinical trials for the drug. 

aldoxorubicin, and forced the company to rewrite its testing protocols and add new patient-screening 

assessments. 

CytRx stock tanked, dropping about 9 percent the day the clinical hold was announced. 

The hold was lifted in January 2015. and by then the company's stock had begun to creep back up, but the 

damage was done. 

The FDA's action sent a chilling message to the industry that trials could be jeopardized by pat1icipating 

in compassionate use. said Steve Walker. cofounder of the patient advocacy group Abigail Alliance, and 

its expert on the FDA regulatory process. 

"That plays into this fear of the drug companies that doing things outside the controlled clinical trials can 

only work against them," said Walker. ··For a small company, an adverse event could not just kill their 

drug. It could kill their company. So they tend to be very conservative when it comes to doing anything 

more than what they have to do in a very careful and controlled way to move their drug towan.l the 

market." 

Walker's wife. Jennifer Me Nellie, died in 2003 of colon cancer at the age of 47 at1er she was unable to 

access potential cures then in clinical trials. 

RISKY BUSINESS 

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60 

Even if a patient's death does not cause a halt in clinical trials. it will likely force the drug developer and 

treating doctor to do an investigation to determine whether the product was to blame, Walker said. 

If it wasn't, that will have to be proven to the FDA's satisfaction. 

If it was, it could further endanger the clinical trials. force new trial designs, or ultimately lead to a 

cautionary warning on the product's label when it eventually is sold. 

That adds time, expense, and investor uncertainty. 

Even people who traditionally defend the FDA and the current regulatory system say the agency must 

address companies' perception that adverse events can endanger final approval of their drugs. 

"They are absolutely afraid." said Caplan. the New York University ethicist. "It's not the company. For 

the little guys, it's the investors ... the people who say. 'I'm putting up money as an early investor in a 

high-risk thing. I may be a big winner. but I'm taking a lot of risk. I don't want the company doing 

anything to make things riskier.'" 

Caplan added that verbal assurances li"om the FDA asserting adverse events will not endanger clinical 

trials is not enough. 

"The FDA should put their approach to interpreting adverse events when they occur in the context of 

compassionate use in writing," Caplan said. "They say. 'We've talked about this at public forums.' That's 

all well and good. Write it down. It's not going to calm fears to say. 'I gave a speech about this and we 

made our position clear.' Write it down." 

Representatives of CytRx would not agree to an interview. 

Neither would onlcials at the PDA. In an email response to questions, Deborah Miller. health programs 

coordinator at the agency. said patients' conditions are taken into account when adverse events in 

compassionate use cases arc evaluated. 

"For the most part, the information is considered anecdotal, outside the context of the trial data." she 

wrote. 

A recent FDA study found that only two drugs out of more than I .000 had their clinical trials suspended 

in a I 0-year period because of an adverse event in a compassionate use case. 

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61 

As to why there is no formal policy, despite concerns routinely cited by industry executives, Miller said 

the FDA is developing guidance "which will provide greater clarity on how the program operates." 

NERVOUS INVESTORS 

Investor nervousness can kill a company. 

Most small drug companies, the ones that tend to be developing innovative treatments to deadly and 

debilitating diseases. live or die on the smooth operation of their clinical trials, according to a review 

of dozens of financial reports filed with the U.S, Securities and Exchange Commission. 

Typically, they have one or two products undergoing trials, and have never had a product approved by the 

FDA or made any money from their new treatments. 

Instead, they survive solely on their ability to attract new money from investors, who arc wary of 

anything that could jeopardize the clinical trials that are likely to go on for years and cost billions of 

dollars. 

SEC disclosures also routinely warn investors about the dangers of adverse events and the stakes if they 

cause a glitch in clinical trials. 

"Adverse events caused by our product candidates could cause us, other reviewing entities, clinical study 

sites or regulatory authorities to interrupt. delay or halt clinical studies and could result in the denial of 

regulatory approval." a company called Chimerix said in its August2015 report to the SEC. "If our 

product candidates arc not successfully developed or commercialized, or if revenues from any products 

that do receive regulatory approvals arc insufficient, we will not achieve profitability and our business 

may fail." 

Chimerix went through the highs and lows of compassionate usc in 2014. 

The company was developing a new antiviral drug called brincidofovir. which had shown remarkable 

improvement from existing treatments in ongoing clinical trials. 

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62 

About 400 patients had been treated with brincidofovir through a compassionate use program, funded in 

part by a government grant to study its usefulness against an outbreak of smallpox. But when that funding 

ceased in 2012, Chimerix slopped accepting new requests for compassionate use. 

MIRACLE CURE 

Meanwhile. 7-ycar-old Josh Hardy was dying. He'd battled kidney cancer since he was a baby. After 10 

intense regimens of chemotherapy, his immune system was depleted. 

Following bone marrow therapy treatment, he developed an infection. His body was too weak to fight it, 

and approved treatments proved inet!'ective. 

Doctors at St. Jude Children's Research Hospital, where Josh was being treated, were aware of 

the potential miracle cure that brincidofovir could represent. In February 20!4. they asked Chimerix to 

make brincidofovir available to treat Josh through compassionate use. The company refused. 

Less than a month later, Josh was in the intensive care unit with renal failure and was not expected to last 

more than a few days. His weakened immune system could not fight off the infection. 

Doctors again requested brincidofovir. Chimerix again refused. 

On March 6, Josh's mother Aimee wrote a Face book post describing his dire condition and the 

company's refusal to help. That touched off a tlrestorm on social media and a public relations disaster for 

the company. 

Chimerix executives were tlooded with cqlli; and em ails demanding Josh be given access to brincidofovir. 

Their personal information and home addresses were posted on the Internet 

There were death threats and stories sympathetic to Josh's plight on the national news. said Kenneth 

Moch, CEO of Chimerix at the time. 

Private security was hired to protect company officials. 

Behind the scenes, there were phone calls between company executives and the FDA, said Debra 

Birnkrant, the FDA official whose unit was in charge of the drug's trials. The agency was unaware of the 

volume of requests for compassionate use access to brincidofovir that the company had been receiving. 

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63 

"I didn't fully understand why in this one particular case this child was not getting access to this drug," 

Birnkrant said at a conference in October in which she appeared on a panel with Moch to discuss the 

ramifications of Josh's case. "In my mind. this was not the case to say no to. The media storm was too 

major. 

By March I I, Chimcrix backed down and allowed Josh to be treated with brincidofovir. He quickly 

recovered. 

About three weeks later, Moch was force,! to resign. 

Josh was not treated through compassionate use. Instead. Chimerix and the FDA devised a wor~-around 

that allowed about 20 patients to be treated in a hastily approved clinical trial that tested the drug's 

effectiveness in treating the type of infection that was killing him. 

Handling Josh's request that way. as opposed to using traditional expanded access. allowed the company 

to benefit in clinical trials from the information gleaned from the patients that were being treated, 

Birnkrant said. 

The dilemma for the 55-person company was that it was deep in debt. had limited financial resources. and 

did not have enough of the drug to provide it to everyone seeking access and still have enough to use in 

clinical trials, according to \!loch and company financial records. 

Getting brincidofovir through clinical trials and approved hy the FDA was deemed the best wav to protect 

the company and help future patients. 

"It's the moral dilemma of the many versus the few. the future statistical people versus the current 

absolute need,'' Mach said. "There was no consideration of the ethical and moral dilemmas in the social 

media program. Social media in this case and in many cases is a public temper tantrum." 

Moch initially agreed to an intcrvie" with the Goldwater Institute but then backed out at the last minute. 

saying he would convey his thoughts at the October conference in which he appeared with Birnkrant. 

While Mach couches the Josh Hardy case as an ethical dilemma, it had tlnancial ramifications as well. 

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64 

Publicity over Josh's quick recovery caused Chimerix stock to soar almost 50 percent. A few months 

later, brincidofovir was used on a compassionate use basis to treat Thomas Duncan, a Liberian man who 

was the tlrst of several patients in the United States diagnosed with Ebola. 

Duncan died in October 2014. And although there was no indication that brincidofovir had anything to do 

with his death. Chimerix stock plummeted by J..i.Qgcent within 30 seconds of the announcement. Mach 

said. 

Company oftlcials still warn of the financial dangers of participating in compassionate use. 

"The risk for adverse events in this patient population is high which could have a negative impact on the 

safety profile ofbrincidofovir, which could cause significant delays or an inability to successfully 

commercialize brincidofovir. which would materially harm our business," the company said in its August 

2015 report to the SEC. 

'SAFER THAT WAY' 

Investor expectations do put pressure on small companies to avoid any risk that could endanger clinical 

trials. including participation in compassionate use. explained Victoria Buenger, who teaches strategy and 

management at the Mays Business School at Texas A&M University and has a joint appointment in the 

school's biotechnology program. 

Chimerix was already deep in debt and its stock volatile before Josh Hardy's doctors made their first 

request for brincidofovir. said Buenger. who helped organize patient advocates to get Josh treatment. 

"It would be very hard to explain to investors why you were going ahead and doing this kind of risky 

behavior when you were already losing money and you were trying to put every bit of effort at the 

company into getting the trials completed so that you can have positive cash flow," Buenger said. "To the 

extent that the stock price is already struggling and you start getting the hint of something that might 

make investors nervous. I think it is a place that becomes very. very strange territory." 

Buenger helped form the Coalition Against Childh.Q<l\LCancer, a patient advocacy group. after the 2009 

death of her daughter, Erin. from neuroblastoma, a type of nerve-cell cancer. 

20 
65 

Companies also face risks when they refuse to participate in compassionate use. Chimerix was besieged 

with negative publicity when it refused to provide Josh the treatment that ultimately saved his life. 

Rightly or wrongly. the company was seen as putting profits ahead of saving a child's life. 

That explains why there is such vehement opposition from the drug industry to disclosing the number of 

compassionate use requests they receive and reject Buenger said. 

"Some drug companies would like there to just be a cloak where you can't see what's happening or even 

ask that question. because it's just safer that way:· she said. 

'SAVING MY LIFE' 

What drug companies hate worst of all is social media campaigns that put a human face on an otherwise 

calculated business decision. 

That's what Andrea Sloan did in 2013 when she launched a social media campaign seeking a cure to the 

cancer that ultimately killed her. In the process. she drew the wrath of one drug manufacturer and inspired 

a push for reform in Congress. 

Sloan was a successful attorney in her late 30s when she was diagnosed with ovarian cancer in 2006. For 

more than seven years, she underwent the standard treatments. She had five surgeries, a stem cell 

transplant, and two full regiments of chemotherapy. Eventually. they stopped working. and she could no 

longer stave off the spread of the disease. 

Her doctors at MD Anderson tirst raised the prospect of compassionate use. 

A new line of drugs was being developed that specifically targeted her type of ovarian cancer and genetic 

makeup. Known as PARP inhibitors. they allow the body to attack cancerous cells without damaging 

healthy tissue. 

Several companies were testing similar drugs. but none were approved by the FDA for use outside of 

clinical trials. 

£3ioMarin Pharmaceutical had reported promising results for its version, BMN-673, in a press release 

aimed at investors and financial media. 

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66 

Sloan met all of the FDA's requirements for compassionate use. When she initially contacted the agency. 

she was told there were no safety concerns about the drug, and her application would quickly be approved 

once BioMarin agreed. 

The company refused. 

BioMarin officials would not answer basic questions, including whom Sloan could talk to about applying 

for compassionate use, according to Sloan·s close tfiend Michelle Wittenburg, who helped her navigate 

the compassionate usc application process. 

"They just summarily turned her down," Wittenburg told the Goldwater Institute. "'She asked and they 

said no, all the while telling their shareholders in investment meetings and documents that they were the 

best thing since sliced bread and the highest performers in this classification of drugs." 

Frustrated and running out of options, Sloan launched a social media campaign to pressure the companv 

to stop stonewalling and allow her compassionate use access to BMN-673. Sloan also started a 

Change.org petition that eventually received about 200,000 supporters. Her battles with cancer and 

BioMarin eventually became nationalnc~c;; and attracted the attention of elected officials in Texas, 

including Congressman McCaul, who authored a compassionate use reform bill he called the Andrea 

Sloan CURE Act. 

"I do have to tell you that I'm a little frustrated at our inability to have an open dialogue about how we 

might be able to get to a solution that both advances your goals of making sure that this treatment is 

available to everyone and advances my goal of saving my life," Sloan said in a video she recorded in 

September 2013, aimed at BioMarin CEO Jean-Jacques Bienaime. 

'SPOILED, PETULANT HRAT' 

Things turned ugly when Bienaime responded directly to Sloan supporters. 

In one emaiL he decried '"a 2.QIDilll'illraJion oft he risks associated with politics and lobbying taking 

precedent (sic) over science." 

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In another, he forwarded a message ti·om someone else saying Sloan "comes across in the media as 

a spoiled, petulant brat'" 

A third and apparently internal email that reached a Sloan supporter discussed the need to hire a public 

relations agency. 

The company was more reserved in ofJ!cial statements to the media. 

"It's our policy to provide access to unapproved drugs only after substantial evidence on safety and 

efficacy has been collected, and registration applications with health authorities are underway," 

spokeswoman Debra Charlesworth told the International Business Times. "The FDA has not approved the 

drug for compassionate usc." 

She did not say whether BioMarin had ever sought approvaL 

A social media campaign was not something Sloan wanted to launch, Wittenburg said. She was by nature 

a private person, so going public was not easy for her, especially to talk about terminal ovarian cancer. 

But BioMarin's absolute refusal to even talk about her options left her no choice. 

"You only pull those triggers when you have to," Wittenburg said. "If there was a more expeditious 

compassionate use, a more navigable and expeditious grant of drugs for someone who is legitimately 

qualified, those things would never be in the press and people would never know." 

A different company developing a similar drug did agree to supply it to Sloan about October 2013, on the 

condition that its name not be disclosed. Nearly three months had passed since she first sought 

compassionate use treatment. 

Sloan responded well at first. But she developed pneumonia, which her body was too weak to fight off 

She died on Januarv I 2014. 

"A company took a chance on her. They gave her the drug and it worked," Wittenburg said. "That is 

wonderfuL It is sad that she did not get it in a timely manner because of the rigmarole of the system. We 

were all clumsy and cumbersome at navigating the system because nobody really totally knew what you 

needed to do, 

"Any delay in time like that when you're terminal, it's a sure-tire killer." 

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BioMarin sold the rights to 13MN-673. now called talazoparib, to Medivation in August 2015, for $410 

million and up to $160 million in additional milestone and royalty payments. 

Sloan would be included in the FDA's 99.5 percent approval rate for compassionate use, despite 

BioMarin's rejection of her requests. Another drug company did allow treatment even though it came too 

late to save her life. 

BALANCING THE RISKS 

After a dying patient finds a doctor and drug company to endorse an application for compassionate use, 

the final hurdle is to get the blessing of the FDA. which has its Q_\VJl set of rules. 

The FDA will determine whether the patient qualities for an ongoing clinical trial. If not. FDA officials 

must agree that the risks of the disease outweigh the risk of administering a treatment that has not been 

fully tested and approved. 

The FDA also must be satistied that treating an individual patient or a small group of patients will not 

interfere with ongoing or future trials. 

Only then will it approve an application and allow a patient to be treated. 

The time and expense of clinical trials created the need for compassionate use. 

The FDA has two missions when it comes to approving a new drug: getting genuine cures to the public as 

quickly as possible, and preventing unsafe or ineffective drugs trom being sold. 

The risk-averse culture at the FDA puts those two missions in conflict. according to critics who say 

agency ofticials are more worried about approving an inetTective drug than getting real cures to patients. 

If the FDA approves a drug that docs not work or has unforeseen side effects. the agency risks a barrage 

of negative media stories and congressional hearings punctuated by anecdotes from patients who were 

harmed. Failing to approve an effective drug may mean more people will die for lack of treatment, but 

those deaths are harder to quantify, and will not happen until sometime in the future. 

"When promising treatments are kept off the market, the patients who fail to benefit go unseen," Avik 

Roy, founder of a health care investment research tirm and a senior fellow at the Manhattan Institute. 

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observed in a 2012 analysis of how FDA regulations stifle innovation in the drug industry. "'What is seen. 

by contrast. are concerns about drugs that were approved by the agency and later turned out to pose 

problems. When this happens. FDA officials are often hauled before Congress and asked to defend their 

decisions. At the agency, expeditious approval of innovative drugs is risky; excessive caution is not." 

Roy would not agree to an interview. 

RISK AVERSION 

The very power of the FDA to regulate the effectiveness of drugs was borne from risk aversion. 

Drugs were essentially unregulated until 1902, when in response to a series of deaths caused by a 

diphtheria vaccine, Congress passed the Biologics Control Act. Four years later, it passed the Pure Food 

and Drug Act that prohibited false or misleading labeling on food and drugs. 

Modern FDA regulation began in 1962, in response to bit1h defects linked to mothers who had taken the 

drug Thalidomide to ease morning sickness. 

Most of those occurred in l:Ctropc. where the drug was commonly used. In the United States, use of 

Thalidomide had been blocked by a single FDA doctor. Frances_Qldham K~. who worried about 

possible side effects. 

Because of Kelsey's persistence. the drug was not sold in the United States. 

Kelsey was hailed as a hero who had saved countless children from horrible disfigurement and was 

presented the nation's highest civilian award by President Kennedy at a White House ceremony. 

Congress also responded by granting the I'D A its modern power to control both the safety and 

effectiveness of new drugs. To prove a new drug worked, manufacturers were required to submit to the 

FDA data from "'adequate and well controlled investigations.'' 

They were also required to repot1 adverse reactions to the FDA. 

The testing process established by the FDA was a simpler version of the trials in use today. But they still 

delayed the time it took to bring a new treatment to market, and drove up the costs necessary to begin 

selling the product. 

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Then came the A IDS crisis of the 1980s. 

People were dying oft he previously unknown disease. There was no FDA-approved treatment to cure it 

or vaccine to prevent it 

A drug known as AZT. originally developed to treat leukemia. was tested on patients with the Human 

Immunodeficiency Virus. or H!Y. which causes AIDS. However. the drug had not been approved by the 

FDA. and therefore was not available under the laws at the time. 

Intense political pressure prompted the FDA to revise its practices. and AZT was made available to AIDS 

patients. Soon patients with other incurable conditions, including cancer. were lobbying for expanded 

access to investigational medications. 

Compassionate use was put into law in I 987. and in 2009 the FDA adopted rules that created the modern 

expanded access program. 

Political pressure changed the Jaw. But it did not change the mindset at the FDA. 

"Every FDA reviewer wanted to be the next Frances Kelsey." wrote Dr. Scott Gottlieb, a former deputy 

commissioner of the FDA and a resident fellow at the American Enterprise Institute, in a 2012 article on 

the agency's risk-averse culture. 

"The episode had a lasting effect on the FDA's work," wrote Gottlieb. "It fostered an idealization of the 

lone reviewer championing an issue of safety against the prevailing orthodoxies, especially when it meant 

taking on corporate interests." 

PHASES OF TESTING 

Clinical trials are 9ivided into three and sometimes four phases. not including the initial research and 

animal testing. 

In phase I, the new drug is given to a small group of healthy volunteers. usually between 20 and I 00, to 

determine if it is safe enough to continue testing. This involves monitoring patients for side effects and 

gaining initial information on dosage levels. 

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Phase 2 is where the drug's effectiveness is tested. Those trials normally include a few hundred patients 

with the disease the drug is meant to treat. Appropriate dosing levels are retined and the product is further 

evaluated for potential safety risks and side effects. 

Phase 3 trials involve hundreds or potentially thousands of patients with the disease. Additional safety 

and efficacy information is gathered to determine whether the risk of the medicine is outweighed by the 

risk of the disease. and whether the new drug is better than existing treatments. 

In some cases, a Phase 4 trial is required to continue monitoring the side effects and effectiveness of the 

drug after it is approved for sale. 

Failure in any phase of trials can mean failure of the product and the company that makes it 

Adverse events in any phase of the trial must be reported to the FDA. which at any time can halt the trials. 

require the protocols to be rewritten. or impose additional screening, testing, or monitoring requirements. 

After all clinical trials arc completed, a tina! New Drug Application is tiled with the FDA. which spends 

months, sometimes more than a year, to decide if there is sufticient data to declare the drug safe and 

effective. Only then can a new medicine he made available to doctors for prescription, and sold for use in 

patients. 

The whole process takes more than a decade on average, according to the Pharmaceutical Research and 

Manufacturers of America (PhRMA), an industry trade and lobbying group. 

HITTING A BULLET 

Once a drug has been approved tor any condition, doctors can prescribe it as they like through what is 

called "off label" use. That means if a drug has been proven effective in fighting. for instance, one type of 

cancer, doctors can use it to treat a different type without restrictions. 

With everything riding on clinical trials. drug companies do everything they can to ensure trials arc 

completed as quickly and predictably as possible. They select patients based on rigid criteria regarding 

health, age, stage of disease and other conditions to remove as many variables as possible that could lead 

to unforeseen reactions. Companies also select test subjects most likely to show positive results, since 

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gaining approval for a single condition is all that is needed to take drugs to market for either the targeted 

disease or any off~labeluse doctors later deem tit. said Walker of the Abigail Alliance. 

"They are literally trying to hit a bullet with a bullet when they design a clinical trial," Walker said. "They 

try to pick a very narrow population of patients that they believe gives them the greatest chance of hitting 

a very small statistical target at the lowest cost and in the shortest amount of time to get that very first 

indication." 

The consequence of that is many patients with terminal conditions do not qualify for clinical trials 

because they are too sick or have other conditions unrelated to the disease itself 

And since drug companies often try to ensure the patients they approve for compassionate use are 

statistically similar to those in clinical trials. someone in an advanced stage of the disease is especially 

unlikely to be approved for treatment, Walker said. 

Kurzrock, the UC San Diego oncologist who used to run clinical trials at MD Anderson, recounted one 

case in which she sought compassionate use for a 19-year-old woman who was dying of cancer and 

deteriorating quickly. All conventional treatments had proved ineffective. and Kurzrock was familiar with 

a particular drug she hoped could save the \\·oman's life. When she contacted the drug company, she was 

told compassionate use would only be allowed if the patient had perfect organ function. 

Fortunately she did, and was approved for treatment. 

Conditions like those. coupled with the convoluted process doctors must go through to file an application, 

can mean the difference between life and death. Kurzrock said. 

"Sometimes an alternative today may not be viable next week, especially if compassionate use demands. 

as in the example I gave, that the patient maintain near perfect organ function," Kurzrock said. "Perfect or 

near perfect organ function is not typical for people dying of cancer. A clinically irrelevant blip in a blood 

test can make the patient ineligible." 

'YOU'RE IN A SLAUGHTER' 

Just such a blip could kill Mike DcRartoli. 

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For 28 years, De8artoli worked as a firefighter, most of it in Sacramento. About three years ago, he 

returned to the station after a fire and noticed cramps in his hand, not an uncommon ailment given his 

profession. 

But the pain persisted. Over the next several weeks, the cramps got worse. Then his tingers began 

twitching. He thought he might have nerve damage. 

What doctors eventually told him could not have been worse. 

DeBartoli had amyotrophic lateral sclerosis. or A LS. more commonly known as Lou Gehrig's disease 

because that is what killed the baseball star. 

ALS is 100 percent fatal. 

There is no cure or effective treatment. 

Before he dies, his body will deteriorate and he will no longer be able to care for himself. 

His life expectancy could be anywhere from six months to five years. 

There was nothing doctors could do. 

"You don't know how devastating it is to face your own death." De Bartoli told the Goldwater Institute in 

a recent interview. "You're in no battle. You're in a slaughter. You have nothing to fight against this 

disease and you just get massacred by it. and you are supposed to just sit there and wait." 

The only glimmer of hope for De8artoli was enrollment in a clinical trial for new drugs being developed 

to slow the progression of ALS. He tried unsuccessfully to get into several. 

He was rejected for one study because his disease was too far advanced. 

Another turned him down because he took medicine for high blood pressure and depression. 

Drug companies want people who are "pure" so they can get the test results they need to get their 

products approved, De8a!1oli said. Those unlucky enough to fall outside the statistical models are left to 

die. 

"They're just studying the drug," he said. "They're not trying to make you better." 

Deba11oli was finally accepted into a clinical trial for an investigational drug that may slow the 

progression of the disease. which he began taking in December. He doesn't know whether it's working. 

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'HORROR STORY STUFF' 

DeBartoli still has another worry: placebos. 

The standard way to test a drug's effectiveness is to give it only to some of the volunteers being tested. 

The rest get placebos (sugar pills. basically) or are treated with existing therapies that may not be 

effective. A drug's success is determined by whether the patients who get the real drug do substantially 

better than those who don't. 

"What we do is ghoulish: it's horror story stuff." said Walker of the Abigail Alliance. ·•Jfyou are in one 

of the trials you are a lab rat. They are going to put you on a sugar pill. and wait for you to die on the 

schedule of an untreated patient for the good of science .... They are willing to waste you to answer a 

statistical question." 

One criticism of both compassionate use and Right to Try laws often cited by the pharmaceutical industry 

is that clinical trials could be endangered if too many patients seek treatment through those means. It is 

couched in terms of the greater good. If people don't enroll in clinical trials. it will take longer for the 

drug to receive f-DA approval and be made available to all patients with a particular disease. That means 

more people in the future will die because of delays caused by efforts to treat patients today. 

"While PhRMA has not taken a position on any of the state or federal expanded access or 'right to try' 

proposals. we have serious concerns with any approach to make investigational medicines available that 

seeks to bypass the oversight oft he Food and Drug Administration and clinical trial process. which is not 

in the best interest of patients and public health." Sascha Haverfield. vice president of Scientific and 

Regulatory Affairs at PhRMA. said in an emailed statement to the Goldwater Institute. 

No one from PhRMA would agree to an interview. 

The industry's arguments are bogus. said Frank Burroughs. who cofounded the Abigail Alliance with 

Walker after Burroughs' 21-year-old daughter Abigailllli'd_of cancer in 200 I. 

Drug companies typically pay for the treatment of patients in clinical trials. a powerful incentive to enroll. 

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The main thing that discourages people from participating is the reliance on placebos, which for most lifethreatening diseases are not needed, Burroughs said. 

Modern technology allows doctors to monitor things like tumor shrinkage in cancer patients. Yet the 

FDA's model has remained relatively unchanged since its inception in the 1960s. Burroughs said. Also. 

doctors and scientists already know the natural progression of most terminal diseases like lung cancer, so 

it makes no sense to continue giving patients placebos to come up with a statistical equation on the death 

rate of those left untreated. 

''If you have a drug that is efficacious in clinical trials. you have people whose length of their lives is 

sacrificed for an unnecessary placebo ann." Burroughs said. 

BARRIER TO ENTRY 

The time and expense of clinical trials means most small companies will be unable to take their product 

all the way from invention to approvaL regardless of its success, according to industry financial analysts 

and some drug company executives. So at some point they are forced to partner with or sell to one of the 

big players in the drug industry. which have the money and regulatory expertise to complete clinical trials 

and navigate the FDA's approval process. 

And that's the way big pharmaceutical companies like it, critics say. 

"The barrier to entry is maintained by Big Phanna," said Woods. who holds over 40 patents for medical 

devices. "They like it that way. They have the money to go and pick and choose what they want to buy. A 

mom-and-pop company has no chance of coming up and competing against my billion-dollar cancer drug 

unless I decide to buy it myself. because they can't do it without me. So they definitely want to maintain 

the status quo. It's in their interest because it will prevent competition." 

Only about 12 percent of the new drugs that enter clinical trials will ever be approved by the FDA for 

sale, according to PhRMA. Of those, about 20 percent generate enough money to cover the cost of 

research, testing. and approval. 

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Cost estimates vary. A Tufts University study. published in 2014 and frequently cited by PhRMA, says 

the real cost of developing a new drug is about $2.6 billion on average, including about $1.4 billion in 

actual out-of-pocket expenses paid by the drug developer. Another $1.2 billion represents the lost revenue 

investors forego because of the long development timeline. 

The most expensive part of the process is Phase 3 testing, which accounts for up to 90 percent of the 

development costs of those drugs that are eventually approved and marketed, according to Avik Roy of 

the Manhattan Institute. 

NEW BUSINESS PLAN 

The ever-increasing cost and complexity of clinical trials spawned a new business model for the 

pharmaceutical industry. said Mark Pauly, professor of health care management, business economics, and 

pul>lic policy at the Wharton business school. 

Twenty years ago, big pharmaceutical manufacturers were in the drug development business from start to 

finish. They had their own scientists who would develop a new product, and would run their own clinical 

trials through all phases and apply for final FDA approval before manufacturing and selling their drugs. 

That proved to be an inefiicient wav of doing business because of high failure rates in early stages of 

testing, Pauly said. 

So rather than inventing their own new cures, most big companies now favor allowing the early research 

and testing to be done at smaller firms that will invent the new product and take it through sufficient 

testing in clinical trials to show it is both safe in humans and more effective than existing treatments. 

Once that has been proven, and there is a strong likelihood the new drug will be approved and turn a 

profit, the big companies will buy the patent rights or the company itseiL 

From the small company's perspective, there is little chance they will be able to raise the billions of 

dollars needed to get their products through all phases of testing. particularly Phase 3, since investors are 

not likely to wait a decade or more before the finn can begin selling the drug and turn a pro lit. 

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"Once the product gets to a stage where it does show sufficient promise, usually in Phase 2, then at that 

point there's this large mountain to climb of FDA approval and Big !'hanna knows how to do that" Pauly 

said of the small companies developing new drugs. "They are mostly founded by scientists. occasionally 

with a visionary venture capitalist. They are not good at dealing with large entities. Now they come faceto-face with that big bureaucracy in the form of the FDA. and they have to be able to cope with that 

alternative environment." 

High research and development costs are driving record levels of mergers and acquisitions in the 

pharmaceutical industry. according to reports from Fitch. 

There are exceptions. 

Some big drug makers still develop and test their own products. 

OveralL about 20 percent of the clinical trials for new cancer drugs are being run by the world's 15 largest 

pharmaceutical companies, according to a Goldwater Institute analysis of a list of investigational cancer 

drugs published bv PhRMA. 

There are also some small companies that have taken their products through the regulatory process and 

become major players in the industry. But those are rare exceptions, according to industry experts. 

BELLS AND WHISTLES 

The new business model works only because of the time and expense of getting through clinical trials and 

FDA approval, said Garo Annen, chairman and chief executive of A genus Inc. Smaller companies may 

have a better drug, but not the money or regulatory expertise to navigate the federal bureaucracy. 

"Are Big Pharma companies sitting down and coming up with this conspiracy'' The answer is they are too 

dumb to do that," Annen said. "Is all of this happening by default? The answer is yes. Of course it's 

happening by default. It's the sweet spot that's been created organically because of all the bells and 

whistles within the system. Do you think Big !'hanna is going to protest against it? Hell no, because it's 

helping them." 

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Pauly agreed that big pharmaceutical companies have an interest in preserving the status quo. since it 

allows them to avoid early research failures and cherry-pick the most promising new drugs. 

··It's certainly true that Big Phanna. which has a Jot of expertise in that model. is not particularly eager to 

see alternative ways of generating information about the effectiveness and safety of drugs brought into 

existence." Pauly said. 

Big pharmaceutical companies have more than the expertise needed to navigate the FDA's regulatory 

system. They have the political muscle to preserve it. 

The pharmaceutical and health products industry is by far jhe biggest spender in federal lobbying. with 

expenditures of more than $235 million in 2015. according to data compiled by the Center for Responsive 

Politics. PhRMA alone spent about $18.5 million. 

One consequence of the industry's new business model is it is even harder for people to get 

compassionate use access to new drugs in early testing. Smaller drug companies are the ones least likely 

to have the money or expertise to make their products available through compassionate use. They also run 

greater risk since they are often reliant on one or two products. and are subject to the whims of investors 

who may panic if there is any glitch in clinical trials. 

"They are generally on a much shorter leash." Pauly said of small drug companies. •·Even now there's a 

lot of money sloshing around at nig Ph anna firms. and they can use it to cover the administrative 

expenses of doing the compassionate use part. 

"In some ways. the fundamental question is why would a profit-seeking firm do compassionate use at all? 

The answer. in large part. is because they want to curry favor. produce a good reputational effect. But 

that's a luxury that many small firms really can't indulge in. Nobody's going to remember their brand 

name anyway. For the most part. a good reputation is more important for a Merck or a Pfizer than it is for 

XYZ Pharma:· 

OBVIOUS RISKS 

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The current structure of the drug industry and pressure from investors does make it tough for small 

companies developing promising new products to treat patients through compassionate use, said Robert 

Erwin, president ofiBio, Inc., a small finn Q_~veloping_lreatments and vaccines using plant-based proteins. 

Money is always tight. There is always the fear that if something bad happens, it could harm the clinical 

trials or scare away investors, Erwin said, adding he believes those fears are overblown. 

Executives at small companies also tend to play it safe because that's what investors expect. 

Their natural inclination is to say no. 

"From the perspective of a small company, the deviation from the standard accepted practice is difficult 

because they have to deal with investor psychology:· Erwin told the Goldwater Institute. "There's a lot of 

comfort in doing what everybody else is doing. So more than the actual economic analysis or an actual 

risk analysis, that comfort of not deviating from the standard is pm1 of the psychological problem.'' 

Erwin has seen the compassionate use debate from all sides. He spent his career as an executive in 

pharmaceutical companies. He came face-to-face with the hurdles of getting potentially lifesaving 

treatment when his wife, Marti Nelson, developed breast cancer. 

Nelson, a practicing physician, underwent the standard treatments. After they all failed, she sought access 

to a drug then under investigation through compassionate use. but she was rejected after what Erwin 

called "the classic runaround." 

Nelson died in 1994 after she and Erwin cofounded the Marti Nelson Cancer Foundation, which helps 

patients navigate the complicated process of seeking early access to drugs that are still being tested. 

Erwin, president of the foundation, also advises patient advocacy groups on technical aspects of the drug 

industry, and sometimes helps drug makers develop their own compassionate usc programs, all without 

charge. 

HIDDEN REWARDS 

Despite the risks, Erwin now preaches to drug companies about the hidden benefits of participating in 

compassionate use. It allows executives and researchers to talk about their products in ways they 

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otherwise could not because of the confidentiality of clinical trials and the federal rules restricting what 

companies can say to investors. Erwin said. 

Success in treating otherwise untreatable patients can create a buzz among doctors and patient support 

groups. especially those who specialize in rare or incurable diseases. 

That is why when big drug makers set up a compassionate use program. they typically will bring in both 

medical and marketing people. he said. 

"They started to sec expanded access as a potential marketing tool," Erwin said. "Companies began to see 

that operating expanded access was a way to tout their product long before it was FDA approved. to 

communicate with thought leaders in their market, and to begin cultivating some experience with the 

product beyond the fairly narrow criteria of the clinical trial population." 

The short-term benefit from success is heightened investor interest. It can also make it easier to recruit 

volunteers for clinical trials. The long-term interest is a built-in brand acceptance of the product when it is 

eventually approved and sold. 

Yet Erwin acknowledges the downsides. including fear of how adverse events will affect clinical trials or 

public perception if a patient dies. 

Even if an adverse event does not cause problems with the FDA. it would likely be something a small 

company would have to disclose to investors. which can make it harder to raise money. Erwin said. 

For a big drug maker with dozens of different products. a single patient death involving one 

investigational drug would not pose a major threat to its tinancial health. But it could devastate a small 

company that has only one or two products. and would have to be reported in its SEC tilings. 

That is often used as an excuse by industry executives and corporate boards unwilling to participate in 

compassionate use out of fear that such treatment could disclose problems with their product, Erwin said. 

In any case, the inclination of executives at small drug companies is still to say no unless there is a strong 

advocate on the inside pushing for expanded access. 

"lt takes somebody to go and present a rationale that they can look at in business terms backed by 

scientific evidence that the rationale makes sense in the context of their particular product." Erwin said. 

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"I view it as a judgment call evaluating risks versus benefits .. The problem is a fundamental problem 

that we're never going to be able to address very well, and that's this risk/benefit analysis and when in the 

process it shifts enough for a company to see it as a favorable prospect." 

RIGHT TO TRY 

Changing that risk and reward equation is not easy. 

Even small attempts at reform have drawn stiff opposition from big drug manufacturers and less-thanenthusiastic responses from the FDA. 

State Right to Try laws are an effort to bypass the federal bureaucracy by hlSjJ]g state Ia \los to give dying 

patients better access to investigational medications. Pushed by the Goldwater Institute and patient 

advocacy groups. the laws have been adopted in 24 states. always with bipartisan support and virtually no 

opposition from lawmakers. 

States have bro<[Q_p.Q.IYJ~.ci to regulate health and safety issues, including the licensing of doctors and 

hospitals. Under Right to Try. patients, doctors. and drug companies decide whether a patient has access 

to a drug being tested in clinical trials if certain requirements are met. The FDA does not have veto 

power. 

The requirements to gualifv for Right to Try vary slightly by state, but arc similar to the federal 

compassionate use requirements. 

Only a patient who has a terminal illness and has considered all available FDA-approved treatments can 

receive investigational medicines under Right to Try. A doctor must agree that the investigational product 

represents the patient's best chance at survival. 

Only drugs that have been shown safe enough to continue testing after Phase I clinical trials can be used. 

and those trials must be ongoing for them to continue to qualify. 

Drug companies are not obligated to provide their products, and can charge for the cost of making and 

administering the treatments. 

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Patients must sign an informed consent form saying they understand the risks of using a drug that is not 

yet approved. and agreeing not to sue. 

Insurance companies are not required to pay for the care. 

No approval is needed from the FDA. 

There are other differences between Right to Try and federal compassionate use. Institutional Review 

Boards do not need to approve treatment under most of the state laws. and patients are required only to 

have considered all FDA-approved treatment options. not to have tried them. 

Critics. including the FDA, warn that treatment with medications that have not been fully tested through 

clinical trials can be d_<!_Qgegllri and could do patients more harm than good. 

But Darcy Olsen, president and chief executive officer of the Goldwater Institute. counters that the basic 

safety of the drugs is established in Phase I trials before they are available under Right to Try. The 

medications dispensed to patients under the law are the same ones now being given to patients in clinical 

trials. 

"The risks are exactly the same as they are for patients who get into clinical trials." said Olsen, author of 

the book The Righrto Trv. "For patients suffering from conditions for which there is no approved known 

cure, the FDA's traditional role of protecting pHtients from drugs and devices that have not yet proven 

effective has little meaning. These medications have already been deemed safe enough to enlarge the 

group of patients involved in the clinical trial to several hundred or even several thousand individuals." 

Both supporters and skeptics of Right to Try laws say drug companies are unlikely to make their products 

available under state laws alone. They are unwilling to risk the wrath of the FDA. which has absolute 

power to prevent their new drug from being approved and sold commercially. 

"They ain't going to do it," Caplan said. "In the real world it's never going to happen. And the other 

problem in the world of really getting access, until you give them some incentive, they're not going to do 

it. There are a few companies with nice leaders and nice boards who would say, 'Okay, we're going to try 

and do this a little bit.' Aut for the most pm1 they're like. 'This is getting me delayed. slowed. I'm not 

paid. I can't deal with this."' 

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CHANGING THE EQUATION 

Olsen believes changes in federal law may be required before there is widespread treatment of dying 

patients with investigational medications under Right to Try or federal compassionate use. Those changes 

should remove the risks drug companies face and create positive incentives to participate, such as 

allowing them to charge for their products and making drugs more available to desperate patients while 

they are still being tested and monitored. 

Similar laws have been in place in Europe for more than 20 years. she said. 

Rep. Matt Salmon. R-Ariz.. introduced a hill last year that would prohibit the federal government from 

interfering with the use of investigational drugs on dying patients under state laws. The bill, which now 

has five cosponsors, was referred to two House committees, but neither has held a hearing on the 

proposal. 

There arc other federal proposals that would make simple fixes to the system. 

Rep. McCaul. the Texas congressman. is trying to force the FDA to issue formal guid.?Jl<:f on how it treats 

adverse events in compassionate usc cases. His bill would require the FDA to "clearly define" how it 

interprets those events. 

That bill is unlikely to pass. However, the provision was included in a broader reform bill called the 21st 

Centurv Cures Act that has bipartisan support and better odds at becoming law. 

Another McCaul proposal that made it into the omnibus bill would require drug companies seeking 

expedited review of their applications under various FDA programs to publicly disclose their 

compassionate usc policies. It docs not dictate what the policy must be. only that the company have one. 

WEIGHT OF EVIDENCE 

McCaul's provisions seek to ease some of the drug industry's worry about pat1icipating in compassionate 

use, but they would not create positive incentives. 

Rep. Morgan Griftith. R-Va., is trying to do that by taking the FDA largely out of the business of 

regulating compassionate usc. 

39 
84 

Griffith has written two bills to allow certain lifesaving drugs in early clinical trials to be prescribed to 

dying patients. One prohibits the FDA and other federal agencies from interfering with the dispensing. 

sale, or importation of investigational drugs or devices to terminally ill patients. The other bill is 

similar but adds restrictions regarding which drugs can be dispensed. 

Both proposals curb the FDA's ability to force drug companies to report adverse events, which would 

help remove some of the risk of participating in compassionate use. 

Griffith believes the best approach would be to allow both good and bad outcomes to be weighed equally 

as anecdotal evidence to supplement data !rom clinical trials. That would begin to create incentives for 

drug companies that really have developed an innovative treatment to help dying patients. because 

success could help them in clinical trials. 

"'We need to be able to say that. good or bad. it comes into the evidence." said Griffith, a lawyer by trade. 

"The weight of the evidence will clearly be much lower than it would from a clinical trial. But the 

evidence comes in. Right now the negative evidence is at least believed to be used by the FDA. but none 

of the positive evidence is. So if you let all of it in. the positive and the negative. and have it at a lower 

level than a clinical trial, it's still a pa11 of the report and a pm1 of the process. then you have some 

benefit.''· 

Big pharmaceutical companies oppose Griffith's bills. Industry representatives have told him the current 

clinical trials system '"is the gold standard of drug regulations and we don't want to mess with that." he 

said. 

"I really have a hard time understanding it. Since I can't understand it, I really can't come up with what 

their motivation would be." 

RAISING THE REWARDS 

Griffith's concept is not new. 

A similar approach was endorsed by the FDA's own science and technolol!y subcommittee in 2007, and. 

on a more limited basis, by the President's Council of Advisors on Science and Technology in 2012. 

40 
85 

Bipartisan bills have been introduced in Congress to create provisional approval since at least 2005. 

The idea is to allow certain drugs that are superior to existing treatments to be prescribed by doctors and 

sold to terminal patients afier they have been shown safe through Phase I testing in clinical trials. The 

testing would have to continue for a drug to be available on a provisional basis, and the drug would still 

need to go through the standard FDA approval process before it could be prescribed and sold to the 

general population. 

Doctors would be able to normally prescribe the medication to patients who meet the requirements. which 

are similar to those for patients seeking compassionate usc. No approval would be required by the FDA or 

an institutional review board. 

Drug companies could charge for the products. allowing them to begin recouping the cost of developing 

the drug and paying to take it through clinical trials. 

If done right. insurance companies would also pay for treatment since the investigational drug would be 

prescribed like any other approwd medication. said Burroughs of the Abigail Alliance. 

Details of various proposals vary. Some would allow provisional approval only after Phase 2 testing. 

Others would allow only drugs that have received an expedited designation from the FDA to be available 

to patients. 

But conceptually. provisional approval would allow dying patients early access to potentially lifesaving 

drugs. allow doctors to treat patients without going through the FDA's red tape. and create a financial 

incentive for drug companies to participate. according to Carla Woods, who produced a documentary 

called Fight to U1·e which describes how the current compassionate use system prevents dying patients 

from getting the care they need. 

In the existing system. small drug developers have to raise money from investors who know there will not 

be any income fi·om a particular product until it passes clinical trials and is approved for sale by the FDA. 

Woods said. Under provisional approval. companies could begin making at least some monev from a 

product after early testing; in three to five years instead of I 0 to 15. That money could be used to finance 

subsequent clinical trials. and create an early income stream for investors. 

41 
86 

That means small drug companies would no longer be forced to sell the rights to their most promising 

products to the big players who are the only ones able to aff(mf the billions of dollars needed to complete 

Phase 3 testing and get FDA approval under the existing system. 

That would completely reshape the pharmaceutical industry. And that's why big pharmaceutical 

companies will do everything they can to prevent it, Woods said, calling it "a game changer" for the 

industry. 

''They will no longer be dependent on getting to market at the whims of Big Pharma," Woods said of 

small drug developers. "!fan independent company gets to market without them, then Big Pharma's 

existing products are threatened. Thus, Big Pharma will do anything to prevent this from happening." 

There are other advantages, both financial and regulatory, suppmiers say. 

It would do away with the "all or nothing" approach that often forces drug developers to abandon 

promising treatments for financial rather than medical reasons. said Roy of the Manhattan Institute, who 

advocates prgvision'!l1ullrq_val of a broader class of medications after Phase 2 testing. 

Provisional approval would also allow data to be collected on both the benefits and risks of a new drug in 

a broader population than is available in the statistically controlled clinical trials, according to an analysis 

from Strategy&, a consulting subsidiary of PricewaterhouseCoopers. 

Calling their plan "real-world evidence," Strategy& recommends allowing drugs to be prescribed 

normally afler basic safety and etlectiveness have been established, sometime during traditional Phase 2 

testing. Data collection would continue. but instead of expensive. lengthy, and highly structured Phase J 

testing, data would be generated by monitoring the much larger population of patients in the real world. 

That would reduce the time it takes to bring a new cure to market by about five years, and cut the cost by 

about 60 percent, according to Strategy&. 

It would be no more risky than traditional Phase 3 testing, because rare safety issues even now arc missed 

before a product is approved, thanks to the limited sample sizes in clinical trials. 

42 
87 

There are other proposals to create incentives for drug companies to participate in compassionate use, 

such as expediting the FDA's review of their drugs or extending their exclusive patents once the products 

are approved for sale. 

ONE LAST SHOT 

Something needs to change. said Mike DeBartoli. the California firefighter who knows he faces a slow 

and debilitating death from Lou Gehrig's disease if he is not allowed at least to try the new treatments that 

could bring hope. 

The current system is a death sentence, he said. 

"I have no hope now. I will take false hope," DeBartoli said. ·'To live the rest of my life knowing that I'm 

not even given a shot. What is that? 

''I don't know who the FDA thinks they are protecting. Who are they to tell me what I should be hopeful 

for or not hopeful tor? You're telling me you won't approve me to take a possible medication that doesn't 

hurt me, that will possibly save my life, because you want to have your fingers in it? I just don't 

understand it." 

43 
88 

Laura Mclinn & Jordan Mclinn 

Testimony for the HSGAC Hearing- Connecting Patients to 

New and Potential Life Saving Treatments 

Thursday, February 25, 2016 10 a.m. 

Hello. My name is Laura Mclinn and this is my 6 year old son, Jordan Mclinn. I will let 

Jordan say hello and he might want to say something else into the microphone. His ears 

are a little more, "mature" now so after he speaks I will let him put his headphones on 

and play on his iPad probably. © 

You may recognize Jordan from a special Christmas wish he was granted in 2014. His 

story went viral after I put together a resume for him to be "hired" at a local fire station. 

The response was overwhelming as he started getting job offers, patches, shirts, letters 

and other gifts from fire departments all across the nation. He had a couple of interviews 

in our home state of Indiana and then found two job offer letters in his stocking on 

Christmas morning. He started going to "work" on a regular basis ... eating meals at the 

firehouses, washing the firetrucks, fixing taillights and taking part in special trainings. He 

has even worked with the firefighters at some Nascar races in Charlotte, NC. At just 5 

years old he was welcomed into a very special family ... the firefighter brotherhood. 

Jordan is living out this dream as a child instead of at the normal adult age. Let's talk 

about why ... 

Jordan was diagnosed with Duchenne Muscular Dystrophy just a few months before his 

4th birthday. It came as complete shock to everyone. The disease is 100 percent fatal. 

To look at Jordan now, you might not even realize he is any different than most 

energetic, active kindergartners. He is super smart, "runs" and plays with his friends, 

has more faith than anyone I've ever known and absolutely loves life. The reality, 

however, is that his muscles are slowly wasting away and without a miracle he will lose 

his ability to walk very soon. Jordan is missing some exons on his dystrophin gene so 

his body is unable to produce this very important protein. As a result, he is getting 

physically weaker every day. Most boys with Duchenne are in wheelchairs before age 

10 and do not live past their twenties. Many do not even make it to twenty years old. 

Duchenne effects 1 in 3,500 boys. Without a miracle Jordan will lose the ability to walk, 

climb, dress himself, feed himself and he will even lose the ability to hug me. Many of 

you in this room are parents. I don't have to tell you how heart wrenching this diagnosis 

is. I also don't have to tell you how fast these childhood years go by for us parents. 

Jordan is in a race with the clock for his life but there is tangible hope at our fingertips ... 

For the first time in the history of Muscular Dystrophy there are promising treatments 

coming up through the pipeline. There are boys who are receiving exon-skipping 

treatments through clinical trials and it is working to slow the progression of the disease! 

These boys are walking, playing soccer, riding bikes as teenagers because of the exon-
89 

skipping drugs they are receiving through these trials. This is unprecedented, unheard 

of in the natural course of this disease. These exon-skipping drugs have no safety 

issues and they are working. Unfortunately, Jordan and many other boys may not get 

access to these treatments in time if we have to wait for the standard FDA approval 

process. Knowing that something exists that is safe and effective gives us hope but it 

also rips our hearts out because he's not able to get it yet. Jordan is already starting the 

decline phase of this disease at just 6 years old. He is getting tired faster, he often cries 

at night because his body hurts, he can't keep up with his friends, he is starting to fall 

more frequently, he can't do the things they are doing at recess and he doesn't 

understand why. We do not have time to keep waiting. With muscle disease once you 

lose function, there is so much damage and it's hard to regain any of that which is lost. 

This treatment is not just a pill he can take at some point in his future and then be okay 

all of a sudden. He needs it NOW, before he declines further. I want to see my son grow 

up. I want to see him be part of the first generation of boys to survive this. And that IS 

possible. Now, let's talk about the barriers and most importantly some solutions for how 

to make this happen ... 

Last spring, Jordan and I helped get the Right to Try Law passed in the State of Indiana. 

Jordan bravely stood in front of state lawmakers and told them to, "Please say yes". And 

they did. It passed unanimously in the house and senate. Our family and Jordan's 

firefighter family was there with Jordan when the governor signed it into law. It was a 

very special day for us because we felt like we had a new hope, kind of a back-up plan 

in case Jordan couldn't get the treatment through a trial or even better through 

accelerated approval. "Right to Try" basically says that if you have a terminal illness 

and a drug exists that could potentially save your life, you have the right to try it before it 

gets approval from the FDA. It has to have made it through a couple of important 

phases with the FDA showing it is safe. You can check out more about "Right to Try" 

and Jordan's story in Darcy Olsen's book, The Right to Try that was released last 

November. Jordan is featured in the chapter, "We are the 99 percent." Even though 

Jordan legally has the "Right to Try" now, the drug company has to be willing to give or 

sell him the drug. At this point, they are not open to doing that. .. for reasons that are 

understandable but not really okay for us at the same time. Maybe the drug companies 

are afraid to get sideways with the FDA and risk their billion dollar investment. I don't 

know. Unfortunately people die in the meantime because no company really knows 

what the FDA will do and the FDA is not really transparent about it. Therefore, the drug 

companies choose to be cautious. Patients deserve the, "Right to Try" to save their lives 

though when options are there. 

I'd also like to talk about another pathway that can help Jordan. Back in 2012 Congress 

passed and President Obama signed the Food and Drug Administration Safety and 

Innovations Acts (FDASIA). FDASIA gave the FDA the backing and support they 

needed to more broadly grant accelerated approval for safe and efficacious therapies 

for rare or severe diseases that meet an unmet medical need, just like the exonskipping drugs I've been talking to you about today ... drugs for rare disease like 
90 

Duchenne. FDASIA mandates that the FDA include the patient voice in their review 

process. Sometime in the next few months there will be patients testifying in front of an 

FDA adcom panel and asking the panel members to endorse the approval of an exonskipping drug that has shown to be safe and efficacious in clinical trials. Now ... we want 

to see the FDA use the tools in FDASIA to grant accelerated approval to potentially lifesaving treatments, starting with eteplirsen, Sarpeta's exon-skipping drug that could 

potentially be approved by the end of May. We need to hear a YES to this safe and 

efficacious therapy from the FDA in May. While this mutation-specific therapy will not be 

able to treat Jordan's mutation, future exon-skipping therapies will. We must start by 

approving these therapies as soon as possible, because Jordan does NOT have the 

time to wait. 

Please, in order to help Jordan and all other boys living with Duchenne, encourage the 

FDA to use the tools you have given them to expedite life-saving drugs to patients. FDA 

has the flexibility and resources needed to approve these life-saving therapies, and they 

must use them in order to save children's lives. Additionally, if you are willing to stand 

with us at that adcom meeting and remind the FDA to use the tools you have given 

them, remind them to listen to the patients on the drug and the patients who want 

access to the drug, our family and the entire Duchenne community would be eternally 

grateful for your support. 
91 

Statement of Diego Morris 

"Connecting Patients to New and Potential Life Saving Treatments" 

February 25,2016 

Good morning Mr. Chairman and members of the Committee. Senator Johnson, thank you for 

inviting me to testify. I am incredibly honored to be with you today. 

I am grateful to have the opponunity to explain my story and tell you why I am dedicated to the 

Right to Try movemenl. 

Four years ago I was a typical II year-old boy. I was playing two spans at the time, baseball 

and soccer. One morning I woke up with pain on the outside of my left knee. I thought it was 

just a typical spons injury. I continued to play in my games and did everything as usual for a few 

days. But the pain would not go away and it was causing me to limp. My mom took me to the 

pediatrician and thank goodness my doctor knew immediately that something was not right. She 

sent me to an orthopedic surgeon the following day for an X-ray. The doctor told my mom that 

he believed I had osteosarcoma. a rare type of bone tumor, just by looking at my X-ray. 

The orthopedic surgeon sent us down to the lower floor for an MRI and my mom called my dad 

and asked him to come right over with my little brother, Mateo. My mom told me much later 

that she felt sick when she saw a technician running out the door. She knew he was running up 

to tell the surgeon of my results. 

Everything happened quickly after that appointment. My parents consulted with many of their 

physician friends about what we should do next. My parents took the advice of our close family 

friends, he is a radiation oncologist and she is a pediatrician. They told my parents I needed to 

have a biopsy as soon as possible at a premier research institution. 

Just three days after my trip to the pediatrician we were on our way to St. Jude Hospital in 

Memphis, Tennessee. We never stopped hoping I did not have cancer. After a long week of 

different types of tests and scans they performed a biopsy. We knew the surgeons would be 

looking at a quick type of analysis they perform in the operating room. They look at something 

called a frozen section during surgery to determine if a person's tumor is cancerous. If the 

surgeons determine it is cancer at that point. they go ahead and place a pon in the patient's chest 

for treatment. When I had barely come out from anesthesia. I whispered to my parents- I asked 

them "do I have a port?" and they said "yes". The three of us cried and my life was never the 

same again. 

After many conversations with physicians, we decided I should stan chemotherapy treatment 

back home in Phoenix, Arizona. My parents came to the conclusion that if I would receive the 

exact same pre-surgery chemotherapy in Phoenix then I should be close to home, in my own bed 

as much as possible, surrounded by friends and family who love me. I received chemotherapy 

for ten weeks at Phoenix Children's Hospital before returning to St. Jude for limb salvage 

surgery. I am so grateful the surgeons were able to save my leg and completely remove the 

tumor. They inserted a signil1cant titanium device in my leg which partially replaced my femur 

and my knee. 
92 

After surgery, the analysis of the tumor indicated that the necrosis, or the amount of the tumor 

killed off by the initial chemo, unfortunately was only fifty percent. The doctors were hoping to 

see at least eighty percent necrosis. This meant that I would need to have a very aggressive plan 

oftreatment. I needed a total oftwcnty-one rounds of chemotherapy, with some of the strongest 

chemo drugs. 

Thank goodness my parent's physician friends never stopped doing research on every available 

treatment for me. They told my parents about a drug called Mifamurtide, or MTP. MTP is an 

immune therapy drug that has improved survival rates for children with osteosarcoma. My 

parents were excited about the drug but quickly realized it had not been approved in the United 

States. MTP was available in so many countries all over the world, they were astonished it was 

not available in America. The trials for MTP had actually been started by physicians in the U.S.! 

My parents flew to Mexico City with our friend who is a pediatrician to sec the results of MT'P 

on their osteosarcoma pa,tients. The doctors there showed them their findings and told my 

parents I was welcome in their hospital to obtain MTP. 

The clock was ticking. In order to have MTP immune therapy I had to start it at the exact time I 

started my post-surget·y chemotherapy- just ten weeks after undergoing significant surgery at St. 

Jude. My parents communicated with physicians in several countries and, after reviewing the 

facts of my case, every oncologist determined I fit the criteria and welcomed me at their hospital. 

My parents never gave up hope they could get MTP in America. They contacted our 

Congressman, the FDA, the drug manufacturer, and anyone they thought could help us find a 

way. They even spoke with the lead physicians for the US trials at MD Anderson and at Sloan 

Kettering. The doctor at Sloan Kettering explained MTP and answered all of my parents' 

questions. He told them there are no guarantees with MTP. My parents told him they weren't 

looking for guarantees- just hope. My dad asked the doctor one last question. He asked whether 

if (God forbid) the doctor's child or grandchild had osteosarcoma, would he take them out of the 

country in order to get MTP? He responded that he would indeed travel for MTP. Little did I 

know that we were about to make a very significant move in record time. 

I will never forget my parents and their friends explaining to me and to my brother that we were 

going to London so I could have MTP treatment along with my chemotherapy. We were so 

upset with my parents at first but ultimately accepted the fact that this treatment might help save 

my life. Our entire family left our home in Phoenix, Arizona and moved 5JJOO miles away. My 

dad commuted between Phoenix and London for nine months and my mom, brother and !lived 

with family in England. Throughout my MTP treatment and chemotherapy my parents continued 

to look for ways to get this treatment at home but it was just not possible. 

My chemotherapy treatment was brutal and I was in the hospital more often than not. My dad 

was always exhausted and hated not being with us when I had to be rushed to the hospital for 

emergencies. My mom was exhausted too, going back and forth between the hospital and home 

to take care of me and my little brother. We were blessed to have relatives in England who 

insisted we stay with them. Many relatives were amazing to us, and showed us so much love and 

kindness. 
93 

But there is no place like home. I felt so isolated. !missed my friends, my home, my puppy and 

my school. 

My family and l were very fortunate to have the resources to relocate to another country to get 

this potentially life saving treatment. Most people do not have that option. When my family and 

l returned to the United States we all agreed we would do anything to help other families not 

have to go through what we did to get treatment, or worse- not to have a promising treatment at 

all. So when the Goldwater Institute asked me to serve as the Honorary Chairman of the Right to 

Try campaign in Arizona !jumped at the opportunity. I am grateful to Darcy Olsen and the other 

people at Goldwater for giving me the chance to do something positive with my terrible 

experience. lam grateful to be alive and I am grateful to be here, with your esteemed Committee 

today. 

Mr. Chairman, members of the Committee, thank you for giving me the opportunity to tell my 

story. I hope and pray we can make it possible for Americans to have easier, faster access to 

critical medical treatment. Please help us give Americans a better chance to save their own lives 

and those of their loved ones. No guarantees -just hope. Thank you very much. 
94 

Joseph V. Guljb, MD, MBA 

United States Senate Committee on Homeland Security and 

Governmental Affairs 

Written Testimony 

Title: Connecting Patients to New and Potential Life Saving Treatments 

Description: 

This hearing will focus on identifYing possible barriers that prevent patients from 

accessing new and potentially lifesaving therapies, often in the face of terminal or 

debilitating conditions. We will hear from patients and experts about the steps 

Congress can take to reduce impediments and help connect willing patients and 

potential medical innovations. 

Witness: 

Joseph V. Gulfo, MD, MBA 

Executive Director, Rothman Institute of Innovation and Entrepreneurship 

Fairleigh Dickinson University 

Visiting Scholar, The Mercatus Center, George Mason University 

Thank you for inviting me to participate in this hearing. I hope that my testimony proves 

useful to the Committee. 

Introduction and Problem Statement 

The Food and Drug Administration has been charged by Congress with a truly daunting 

responsibility with respect to drugs, biologics, and medical devices - to approve 

products that are safe and effective. The mission of the Food and Drug Administration 

(FDA), as stated in the Food, Drug and Cosmetic (FD&C) Act, is to: 

"promote health by promptly and efficiently reviewing clinical research and 

taking appropriate action on the marketing of regulated products in a timely 

fashion." This includes "ensuring that ... (B) human and veterinary drugs are 

safe and effective; (C) there is reasonable assurance of the safety and 

effectiveness of devices intended for human use." 

Safety and effectiveness are the sole criteria that FDA is to use in determining which 

new products should be approved. In addition, Congress implied urgency to this 

function by using three key words- promptly, efficiently, and timely and called for 

the FDA to be forward-looking- promote health and not simply content with 

preserving the status quo. 

However, we have seen progressive erosion of the safety and effectiveness cornerstone 

upon which FDA law has been built, and with that erosion, a loss of urgency to deliver 

safe and effective products to patients. 

Safety and effectiveness arc difficult enough to determine, and the FDA deserves our 

respect and admiration for the work that it performs along these lines. How much more 

February 22, 2016 
95 

Joseph V. Gu/fo, MD, MBA Written Testimony 

difficult and often impossible are other criteria and unrealistic expectations that have 

been wrongfully laid at FDA's doorstep? 

The expectation from certain areas of society is that the FDA completely defines the 

clinical utility, clinical outcomes, and benefit-risk of new drugs, and vets all potential 

side effects for all people in all situations, even effects resulting from uses that are not 

intended and are not in conformity with approved labeling. Such an expectation is not 

just impossible to satisfy-it is entirely unreasonable. When we consider that conflicting 

studies continue to emerge about health outcomes related to coffee and red wine, which 

have been in use for thousands of years, we can see the absurdity of expecting the FDA 

to somehow anticipate, unerringly, all possible health outcomes from the use of new 

drugs. 1 

Due to fear and pressure from the media, members of Congress, and others, the FDA 

does not take as its starting point the view of doctors who are on the front lines of 

patient care and of patients. Instead, over the last 20 years, the FDA has become 

markedly more restrictive concerning new drugs, particularly through its efforts to 

anticipate clinical outcomes of drug treatment (as opposed to surrogate or intermediate 

endpoints, amelioration or reduction of signs and symptoms of disease, biomarkers, 

etc.). 

As Figure 1 depicts, fear has caused a shift in FDA posture from promoting health to 

protecting health. With this shift, the safety and effectiveness standard has been 

dramatically changed - safety no longer applies to the use of the drug according to 

conditions of use contained in the label and effectiveness no longer means substantial 

evidence of disease activity. In the fear-based paradigm, safety is determined by 

projected benefit-risk and effectiveness requires proof of clinical utility, outcomes and 

survival. 

'Searches of the National Institutes of Health's PubMed research database for "coffee consumption" 

(http://www.ncbi.nlm.nih.gov/pubmed/?Db~pubmed&term=coffee%2oconsumption) and "red wine 

consumption" (http:/ jwww.ncbi.nlm.nih.gov/pubmed/?term=red+wine+consumption) turn up hundreds 

of studies. 

2 

February 22, 2016 
96 

Joseph V. Gulfo, MD, MBA Written Testimony 

Figure 1. Fear-based shift in emphasis to protect health and associated changes in the meaning of 

safety and effectiveness 

Congressional mandate to 

promote health 

(Food, Drug and Cosmetic Act) 

A 

s.:1fety effectJveress 

~ + 1 sate when used lf'r 

ClCCOfdClnce With 

i labeled conditions ;;mel 

mstrurt:ons 

OC!IVIty 111 modUI?.tlf'rQ t!'l!? 

d1sease (phamacolog1c 

cilnJCal, patJenHeportecl. 

b1omarker 

Safe and effectrve products are mdde ava:!able to 

the med:cal marketplace for real·world use. Drugs 

are vetted and best drugs selecte-d basea O'l Jeal· 

world clm!cal ut1l1ty <n tnd!VIdual patients 

FDA's assumed primary emphasis on 

safety 

~ effectiveness 

~ effect1vene! defmed by 

s.Jfety ultnnate clinical utility m large 

determined by populat1orrs of pat1ents 

benefit/risk unp10vement 10 disease 

evaluntton mod1f!catron outcomes and 

' 

surv1val of the "average pat1e11t 

Ji 

EpidemlokJQiCCll-scale studJes 

determine optimal pract1ce 

Drug use and disease 

~ rtli1nager1ent are 

diCtated to the tnf.>d!CCll rnarketpl{1ce 

The effect of the fear-based increased restrictiveness verges on telling doctors how to 

treat patients, as though the regulators arc to prescribe drugs remotely from Silver 

Spring, Maryland. The FDA is applauded by many, particularly those who have 

misinterpreted the rise of an academic movement known as evidence-based medicine 

(EBM), when it purports to debunk medical practice on the basis of the humongous 

clinical trials that it requires drug companies to perform as a condition for approval. 2 

And so the trend has been for the FDA to become more and more restrictive, protracting 

its pre-approval processes and now frequently requiring that additional controlled trials 

be done after approval.:l 

This fear stems from unreasonable expectations of perfection from certain segments of 

society. Fear of being blamed for the failings of approved products has caused the FDA 

to be too cautious in its reviews and approvals.4ln a sense, the FDA has restated its 

mission from promoting health to protecting health-from permitting new safe and 

effective products that can advance health to demanding certainty that products will 

improve clinical outcomes and will not cause any harm. However, as drugs are small 

'Matthew Herper, "Robert Califf Could Transform the FDA-the Right Way," Forbes, September 16, 

2015, http:/ /www.forbes.com/sitesjmalthewherper/2015/09/16/robert-califf-could-transform-the-fdathe-right-wayj. 

:1 Michael Dickson and .Jean Paul Gagnon, "Key Factors in the Rising Cost of New Drug Discovery and 

Development," Nature Reviews Drug Discovay 3, no. 5 (May 2004): 417-29. 

February 22,2016 

3 
97 

Joseph V. Gulfo, MD, MBA Written Testimony 

molecules designed to have an effect by binding to targets in the body, it is impossible to 

give assurance that no harm will ever occur. 

Of course, protecting health is part of promoting health, however, the FDA has elevated 

"protecting" health as its main mission. Promoting and protecting health are two 

different postures - the latter looks to preserve that which currently exists while the 

former engenders optimism and belief in the advancement of scientific discoveries as a 

means of improving the health of Americans. Implicit in promoting health is an 

understanding that occasionally new products may not be found to be as desirable as we 

would like them to be, however, the only way to have genuine progress is to accept and 

deal with "bleeding edge" issues as we try to bring cutting-edge treatments and 

diagnostics to patients as soon as possible. 

The Primacy of the Scifety and Effectiveness Standard 

The law reinforces the primacy of safety and effectiveness in FDA's decision-making as 

evidenced in the language of C.F.R. Title 21, Chapter 1, Suhchapter D, Part 314, Subpart 

D, Section 314.125(b)(2)-(5), which lists permissible reasons to refuse an application. 

Specifying reasons for refusal implies that approval is the anticipated (or hoped-for) 

outcome: 

(3) The results of the tests show that the drug is unsafe for use under the 

conditions prescribed, recommended, or suggested in its proposed labeling or the 

results do not show that the drug product is safe for use under those conditions. 

(5) There is a lack of substantial evidence consisting of adequate and wellcontrolled investigations, as defined in 314.126, that the drug product will have 

the effect it purports or is represented to have under the conditions of use 

prescribed, recommended, or suggested in its proposed labeling. 

By listing the specific deficiencies for which approval can be withheld, as opposed to 

conditions that must be met for approval to be granted, the law clearly presumed 

approval to be the likely outcome. This makes sense because in order for review dossiers 

to be submitted, drugs (hereinafter inclusive of drugs, biologics, and medical devices) 

must first survive the low probability and roughly decade-long rigorous gauntlet of 

preclinical testing, early clinical development, and large late stage trials for sponsors to 

feel confident that the drugs meet the safety and effectiveness standard. 

Safety and Effectiveness Does Not Mean Clinical Utility, Benefit-Risk, 

Survival, or Comparative F.ffectiveness 

Notably absent in the law is any description of refusing an application on the basis of the 

FDA's predictions as to how benefit-risk assessments will be made by an "average 

patient" and the patient's physician. The agency has also departed from the statutory 

language by considering possible uses outside of the labeled uses. The law states that the 

FDA is to judge a drug's safety, on the basis of "tests" and "investigations," in the context 

of the "conditions of use prescribed, recommended, or suggested in its proposed 

4 

February 22, 2016 
98 

.Joseph V. Gulfo, MD, MBA Written Testimony 

labeling." This expressly does not include possible off-label uscs.s Yet the FDA now 

asserts that it "must also consider how people will actually use newly approved drugs 

once they are marketed," using "methods from social and behavioral science" to 

anticipate "cognitive and behavioral factors affecting human judgment and decision 

making in the context of health care delivery."6 It is now commonplace for FDA 

guidance documents to stray, not only from the statutes passed by Congress, but also 

from the FDA's own rules. This is how the safety and effectiveness standards have been 

progressively eroded and changed over time. 

Benefit-risk is a private health decision to be made by doctors and patients when 

weighing whether to use drugs that are safe and effective (public health decision) see 

Table 1. Interestingly, the criteria of safety and effectiveness are relative to that which 

the sponsor claims in its proposed labeling, not in the absolute. All drugs have side 

effects -the FDA's job is to label products appropriately so that they can be 

administered safely to patients for which they are intended. Benefit-risk is more of a 

labeling issue (relative to FDA's responsibility) than it is a basis for approval, yet, 

benefit-risk has seemingly supplanted safety and effectiveness as the operating approval 

standard. 

s C.F.R. Title 21, Chapter 1, Subchapter D, Part 314, Subpart D, Section 314.125(b)(2)-(5). 6 FDA, Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making: Draft 

PDUFA V Implementation Plan, February 2013, 2. 

February 22, 2016 

5 
99 

Joseph V. Guljo, MD, MBA Written Testimony 

Table 1. Public Health Decisions (made by FDA) versus Private Health Decisions (made by patients and 

physicians) 

Health decision Public Private 

Primary considerations safety and effectiveness benefit/risk 

Main question whether the drug under review whether the likely benefits 

can be labeled for safe use outweigh the likely risks of 

under conditions proposed by using the drug in the patient 

the drug sponsor presenting to the physician 

Responsibility FDA physicians in the medical 

marketplace 

Inputs into decision clinical trial results in regulatory the personal profile of the 

filings patient under treatment, drug 

labeling, personal experience, 

literature, peer consultation 

Contribution of drug determination of drug activity clinical outcomes of individual 

intervention to the decision (pharmacologic, clinical, patients treated with the drug: 

patient-reported, biomarker, improvements in survival, 

surrogate endpoints-related) in patient-reported outcomes, 

modulating disease in the reduced morbidity, improved 

"average patient" tolerability 

Extenuating circumstances conditions for which no other I patient preferences 

therapies exist I 

The use of benefit-risk opens the door for FDA to make determinations regarding 

clinical utility (proof that the treatment positively modulates disease outcome) and 

clinical benefit (proof that the effect of the drug enhances the patients' lives). This 

completely changes the nature of pre-approval clinical trials because in order to provide 

substantial evidence of clinical utility and clinical benefit, even larger health outcomes 

trials and comparative effectiveness studies are necessitated in the premarket drug 

approval process. Although "benefit-risk" sounds like a fine construct upon which to 

make determinations about the usefulness of new drugs, it is not (at least for the FDA). 

Rather, it ushers in consideration of a new drug's utility in clinical settings, which leads 

to a demand for data on hypothetical patient outcomes.? While clinical trials can readily 

show whether a drug is active in modulating disease parameters (lowering glucose 

levels, reducing pain, reducing tumor burden, etc.), however, even the largest trials 

cannot control for the m}Tiad factors that affect ultimate outcomes (survival, reduction 

in end-organ complications, etc.). Choosing to base FDA decisions on benefits and risks 

implies that the FDA will take on the decision roles of physicians and patients, 

attempting to anticipate or predict their future choices. Requiring comparative 

7 The word benefit naturally leads to the question "to whom?" By contrast, the word effective naturally 

leads one to ask "for what?" Couching the matter in terms of effectiveness thus tends to promote a focus 

on what it is that the drug under study can or cannot do, while couching it in terms of benefits tends 

toward speculative imaginings about patient circumstances (e.g., constructs such as "the average patient") 

and other unbounded consideration of matters beyond the regulator's expertise and awareness. 

6 

February 22, 2016 

I 

I 
100 

Joseph V. Gulfo, MD, MBA Written Testimony 

effectiveness trials is a logical but unfortunate consequence of such an attempt because 

someone must choose among drugs. Requiring comparative effectiveness trials further 

adds to the cost and time it takes to develop new drugs. If required to better inform 

medical decision-making, benefits and risks, and comparative effectiveness, can and 

should be analyzed post-approval, in the medical marketplace. If certain payers demand 

comparative effectiveness trials, it need not be an FDA function to oversee such trials. 

Evidence Based Medicine Should Not Replace Private Health DecisionMaking 

Despite incessant pleas from doctors and patients for more safe and effective products 

that might help when used appropriately, the FDA continues to raise the evidentiary 

threshold for permitting a new product-recasting prcmarkct approval as a venue for 

the practice of evidence-based medicine to determine clinical utility, benefit, and health 

outcomes, pre-approval. This move is aimed at satisfying FDA critics, but it consumes 

precious time and resources, and it dissuades drug developers (and would-be 

developers) from pursuing projects. 

The FDA has acknowledged the changes in its standards for product approval. In a 

March 10, 2015, opinion piece, two high-ranking FDA officials had this to say about the 

review process: "It is important to remember, however, that innovative therapies only 

save lives if they work properly. U.S. citizens rely on the FDA to ensure that the drugs 

they take are effective and that their benefits outweigh their risks. Improving a patient's 

l(fe or lifespan must be central to the concept of drug innovation." 

But the FDA is supposed to assure safety and effectiveness of drugs, not life outcomes 

for patients. A drug's proposed label indicates the effect it is purported to have; safety 

and effectiveness arc to be determined in the context of that labeling. The physician and 

the patient, acting in the medical marketplace, are to determine whether and when 

taking the drug will be conducive to improving a patient's life. That we authorize 

physicians to prescribe drugs off-label is indicative of this division of labor. 

Certainly, studies of life outcomes can be invaluable to informed decision-making by 

physicians and payers. But there arc many and varied factors that contribute to disease 

development, progression, and response to therapy. It is far harder to produce good 

knowledge about life outcomes for patients than it is to produce good knowledge about a 

drug's safety and effectiveness with respect to specific disease-related parameters. 

Moreover, the appropriate place to evaluate life outcomes is in the post-approval setting, 

by the medical marketplace. Trying to do so pre-approval, before a new drug has settled 

into practice, is not scientifically prudent. The myriad of real world factors that may 

modulate ultimate clinical benefit cannot be known or controlled in pre-approval 

studies, no matter the size, without informed data that become available only after a safe 

and effective drug has been in use for a period of time. Thus, the way that FDA currently 

approaches drug approval can actually mask clinical benefit. If clinical utility is used as 

the criteria for approval, many drugs that are safe and effective and could help patients 

will never see the light of day. 

7 

February 22, 2016 
101 

Joseph V. Gu/fo, MD, MBA Written Testimony 

In fact, using life outcomes in clinical trials introduces a significant probability that a 

positive effect of the drug will be missed (false negative). The FDA cares more about 

reducing the chances of trials showing that there is a meaningful difference between 

treatment groups (new drug versus an alternative) when, in truth, there is no difference 

(false positive). In reality, patients (particularly patients with terminal illnesses) care 

more about trials missing a potential meaningful effect (false negative) -they would 

rather have more safe and effective products that could possibly help them than fewer 

products that are likely not inferior to other treatments. 

How is Precision Medicine Best Practiced? 

The other problem with the FDA's current approach is that it is directly contrary to the 

precision medicine movement. The FDA makes its determinations based on the 

responses of the average patient in clinical trials. While immediate- and near-term 

measures of effectiveness (reducing pain and tumor size, and increasing air movement 

in the lungs, for example) are appropriately evaluated by calculating average patient 

responses, clinical benefit is not appropriately assessed in this manner. Many patients 

may truly benefit from a drug, however, the benefit may not be seen in enough patients 

to pass the average patient hurdle. As long as the drug is safe and effective as per its 

labeled conditions of use, clinical benefit should be the domain of patients and doctors, 

not of the FDA. 

In essence, the FDA, which should be the gatekeeper of safe and effective products that 

enter the medical armamentarium, has put itself in the position of judging which drugs 

arc most beneficial. The funnel diagram in Figure 2 depicts the roles and responsibilities 

of medical marketplace constituents in the diffusion of new drugs and devices into 

practice. The law provides for the FDA to be at the top of the funnel and for the medical 

marketplace to decide from among the FDA-approved safe and effective products which 

are the most beneficial, therefore, which are used the most (bottom of the funnel). 

However, the FDA in demanding data from drug developers, pre-approval, to determine 

which drugs are most beneficial, is putting itself at the bottom of the funnel, as well. 

8 

February 22, 2016 
102 

Joseph V. Gulfo, MD, MBA Written Testimony 

Figure 2. The Medical Ecosystem & Marketplace- Appropriate Roles 

FDA 

earlY adopter phySICians 

* physicians and patients 

payers, pattent advocacy 

and cooperative groups, and 

drug compantes 

new drugs. bto!OgJcs, devtces Approve safe and effective products. 

Identify product uses tMt y1eld good results and low toxiCity. Md share best proctices among chni<:Jans. 

Use onhne profeSSIOMie~nd socta! networks to share expenences with 

new produ<:ts and how to achteve good results. 

Internet of Thmgs Gather data, enable rapid data querying for truly personah:zed medicine. 

and make genomfC proflf!J"'Q rout1ne 

Widespread use Use products appropnately for best possible outcomes. 

At no other time in history have we been better equipped to perform real-world, largescale outcomes and survival studies with regard to medical interventions, such as the 

use of safe and effective drugs and devices. There is no way that pre-approval studies of 

drugs and devices, in tightly defined patient populations under scripted medical 

management protocols, can produce the kind of evidence that is available through realworld data acquisition and the Internet of Things. What's more, in the post-approval, 

real-world setting, data that will enhance the selection of therapy for an individual 

patient can be made available in an unprecedented manner, which can truly drive 

personalized medicine. 

Patient Centered Development 

There has been a great amount of discussion centered around the goal of bringing the 

voice of the patient into the development of new products. In the PDUFA VI meetings in 

October 2015, a proposal for advancing the science of patient input (Patient Focused 

Drug Development and Patient Reported Outcomes) was discussed. As summarized in 

the meeting minutes8: 

FDA identified a need to bridge learnings from PDUFA Vpatient-focused drug 

development-type meetings to the development of methodologically sound fitfor-purpose tools to systematically collect key information about patients' 

experience including the burden of disease, and benefit as well as potential 

burden of thempy. To address this FDA proposed to use public workshops to 

8 FDA-Industry PDUFA VI Reauthorization Meeting- Regulatory Decision Tools Subgroup 

October 7, 2015, 12:3oam-2:30pmFebruary 22, 2016 

9 
103 

Joseph V. Gulfo, MD, MBA Written Testimony 

develop a series of guidances focusing on recommended approaches including 

collection of comprehensive patient-community input, impacts that are 

important to patients, and the measurement of those impacts. FDA noted 

that the capacity for increasing patient engagement and review work would 

require increased staffing. 

These efforts have been fruitless to date and are unlikely to yield substantive change. 

Existing laws, rules, and guidance documents provide for the use of patient-reported 

outcomes, for example, pain scales and activities of daily living. The best way to bring 

the voice of the patient into development and approval decisions is to not presume to be 

capable of ascertaining the voices of individual patients. These efforts are likely to end 

up being representative of the fictional average patient. Patient preferences are highly 

personal and diverse and as such, the assumption that the FDA can make these 

decisions on behalf of patients is unsound. These decisions are appropriately made by 

patients and their physicians as they decide on which (and whether) available safe and 

effective products will be employed to help them, not by the FDA. 

It is imperative that the FDA get back to focusing on safety and effectiveness as the preapproval standards. The flow of new innovative therapies that can advance health is 

dependent upon all players in the medical marketplace performing their role, starting 

with the FDA making safe and effective products available. Acknowledging that 

medicine is more of an art than a science and that the FDA is not the lone participant in 

the medical ecosystem responsible for advancing the health of Americans is the first 

step. 

The Vicious CtJcle that Erodes Safety and Effectiveness Standard 

As former FDA Commissioner Alexander M. Schmidt said in 1974: "In all of FDA's 

history, I am unable to find a single instance where a congressional committee 

investigated the failure of FDA to approve a new drug. But the times when hearings have 

been held to criticize our approval of new drugs have been so frequent that we aren't 

able to count them. The message to FDA staff could not be clearer." Castigation and 

public embarrassment of the FDA when unfortunate issues with approved products 

emerge as they are used in larger real world populations is the first step of the vicious 

cycle that has eroded the safety and effectiveness standard. 

Congressional oversight has been exercised more as a "fire alarm" than as "police 

patrol," in the words of McCubbins and Schwartz.9 Congress has been deficient in 

"police patrol" oversight, that is, constant watchful vigilance to ensure that FDA laws are 

enacted dutifully. But, it has been quite aggressive in exercising "fire alarm" oversight in 

response to events like adverse reactions with medical products. 

There have been many high-profile hearings on drugs including antidepressants, Vioxx, 

Rezulin, and Avandia. In all of these, the FDA is basically accused of inappropriately 

9 Congressional Oversight Overlooked: Police Patrols versus Fire Alarms. Mathew D. McCubbins and 

Thomas Schwartz. American Journal of Political Science. Vol. 28, No. 1 (Feb., 1984), pp. 165-179 

February 22, 2016 

10 
104 

Joseph V. Gulfo, MD, MBA Written Testimony 

approving products that are unsafe. Of course, the issues are not so cut and dry. This 

kind of knee-jerk oversight, which provides great, significantly damages the cause of 

medical innovation. 

The case of Avandia is particularly disconcerting- even when the FDA does the right 

thing, for example, approving an excellent drug that helps millions of patients, it is 

castigated and publicly humiliated. In 2007, a New England Journal of Medicine 

publication of a meta-analysis of 42 small clinical trials revealed an increased likelihood 

of significant cardiovascular toxicity in patients taking the drug, so the FDA restricted 

the drug's use in response to pointed criticism at a Congressional hearing. Here is what 

the FDA had to endure at a Senate hearing on the matter: 

"This report poses several troubling questions for this subcommittee. Most 

obviously, if Avandia is unsafe, how did it ever get on the market in the first 

place? For that matter, why is it still on the market, right now? And what does the 

case of Avandia tell us about the FDA's current ability to conduct its drug safety 

responsibilities?" 10 

Subsequently, the FDA removed the restrictions from the label when the drug was 

shown not to cause increased cardiovascular problems, following a re-analysis of a very 

large prospective study, rendering the meta-analysis flawed. But the damage was done -

the FDA changed the regulations to require larger and larger clinical trials and disease 

outcome endpoints for products that are intended for large chronic diseases, like 

diabetes. Knee-jerk oversight triggered by a flawed analysis had severe unintended 

consequences. 

Sadly, Dr. Robert Califf, nominated to be the new FDA Commissioner, was in full 

support of erroneously demanding larger and larger trials in the midst of the Avandia 

saga - As Matt Herper of Forbes writes: 

"In 2008, after Steven Nissen from the Cleveland Clinic had openly criticized 

Avandia, the GlaxoSmithKiine diabetes drug, he proposed a new standard for 

studying diabetes medicines that would insist they be tested in clinical trials 

involving thousands of patients to see if they had any effect on heart attack rates. 

When Nissen mentioned the idea at an open public meeting, Califf was fast to 

back it."11 

And, these sorts of unnecessarily large, expensive, and time-consuming studies have 

remained as the new standard- they were not walked-back when the case of Avandia 

was shown to be a false alarm. In December 2015, the FDA issued the following 

statement- "continued monitoring" of Avandia, Avandamet and Avandaryl had turned 

up "no new pertinent safety information" about the drug. So, the agency lifted the final 

layer of safety measures that it erroneously imposed. But, sales of the drug were crushed 

as reported by FiercePharma, "The safety questions drove Avandia revenues down 

w Medscape. Avandia and FDA Both Subject of Severe Criticism at Congressional Hearing. May 11, 2.010 

"Forbes. Robert Califf Could Transform the FDA The Right Way. September 16, 2015 

February 22, 2016 

11 
105 

Joseph V. Gu/fo, MD, MBA Written Testimony 

from a peak of $3 billion before the controversy to $183 million in 2011, just before 

generics hit the market." 

At the Senate HELP (Health Education Labor and Pensions) committee's confirmation 

hearing for Dr. Califf on November 15, 2015, he doubled down: 

Sr. Warren:" Do you agree with arguments to lower standards for FDA approval 

of drugs and devices?" 

D. Califf: "I have never been a proponent of lowering standards for 

anything, . .I have been in favor of raising standards. In no case 

would I argue to lower the standard. I think I have been staunch in 

that regard."12 

It is understandable that the FDA would recoil when it is attacked. The agency then 

protects itself from future attack by: (1) raising the bar for product approvals by moving 

away from the statutory criteria of safety and effectiveness and demanding proof of 

clinical utility, clinical outcomes and survival; (2) demanding larger and larger trials 

that cost tremendous amounts of time and money; (3) shifting its emphasis to preapproval requirements versus a balance of pre-approval data and post-market controls 

and surveillance; and (4) preferentially approving products for niche diseases rather 

than those that affect millions of Americans. (See Figure 3, which depicts the Vicious 

Cycle.) 

After FDA recoils in response to criticism and then issues new rules and guidance 

documents with alternative interpretations and implementations of the laws, Congress 

does not perform the appropriate police patrol oversight to re-direct the FDA back to its 

mandate, forcing the FDA to honor the letter and spirit of the laws. No, it does 

something worse- it actually passes more laws, for example, as part of each PDUFA 

(Prescription Drug User Fee Act) and MDUFA (Medical Device User Fee Aet) 

reauthorization that takes place every five years, and in other legislation, like 21st 

Century Cures. This legislation, drafted in consultation with the FDA, then codifies the 

FDA's new positions taken in response to inappropriate fire alarm oversight. 

" BioPahrma Dive. Senators grilled Ohama's nominee for FDA chief. Here's how he responded. November 

18,2015 

12 

February 22, 2016 
106 

Joseph V. Gulfo, MD, MBA Written Testimony 

Figure 3. The Vicious Cycle the Progressively Erodes the Safety & Effectiveness Standard 

The vicious cycle starts over again the next time unfortunate adverse events occur with 

drugs and devices that are on the market, which invariably happens. This is how 

regulation kills medical innovation and hurts patients. With each turn of the vicious 

cycle, the safety and effectiveness standard is further eroded along with the nature and 

balance of pre-approval criteria and post-approval controls. Figure 4 demonstrates how 

the balance of pre-approval requirements and post-approval controls is shifted with 

each turn of the vicious cycle. It also demonstrates how the nature of the pre-approval 

requirements and post-approval controls are modulated. 

February 22, 2016 

13 
107 

Joseph V. Gu/fo, MD, MBA Written Testimony 

Figure 4. Shift in balance and nature af pre-approval requirements and past-approval controls as the 

vicious cycle erodes the safety and effectiveness standard 

FOA Law provide.. 1 .• 

1

. 

balance between pr&- . 

approval requirements I and post*morket controt~J 

Pre-approval 

Pre-approval 

requirements 

Po5J: ·itpproval c<mttcls (studies, 

Vigildnte, s.utwi1laoce) 

• ?re,a.ppro\lel Drug stud res longer, larger, and m-ore 

expe~~we 

Race toward mche Cl!lims. and reguiatory inc-entives 

{Orphan Drugs, Br.a~through Thorapy, Fast Trad<, 

Pnonty Revit'\V. Acce+erated Appr-oval) 

Po,st·apprcva! r~quirements re:tnt~•nf With dawbad. -•f 

s.urvtva! and. dise-a.se- O\.ltcome endpoints not met, can remove 

from market even if still "effective"' 

fewer approva.tsof drug-s affe-ctmg d!W"3Se1 that af~t mdlions of 

Amentans. .. 1-e-M mnovatk>n whe-re tt can have the most tmp.act 

Rise of Specially and Orphan Drugs in Lieu of Drugs Treating Diseases 

with Large Populations of Patients 

A direct outcome of this vicious cycle is the rise of specialty pharmaceutical products 

intended for small populations of patients. In 2014, the FDA approved 41 new drugs 

more than in any year since 1996, according to the agency's numbers. In 2015, 45 novel 

new drugs were approved. Many have cited these statistics as proof that the agency is 

performing well, consistent with its mission since the 2014 total was more than double 

that of 2007. However, 40% and 47% of the drugs that were approved in 2014 and 2015, 

respectively, were for niche orphan diseases, that is, conditions affecting less than 

200,000 patients per year. There were 467 requests for orphan designation last year by 

the pharmaceutical industry ( -35% increase from 2013), and 293 drugs were granted 

orphan status by the FDA (13% increase). 

Given these statistics, it becomes obvious that the industry's focus on niche specialty 

drugs as opposed to drugs for diseases that affect millions of Americans is driven by the 

erosion of the FDA's safety and effectiveness standard for approvals. 

The FDA, following public ridicule in oversight hearings of drugs for diabetes and 

arthritis, has imposed new standards for approval- not only must drugs for diseases 

that affect millions of Americans (diabetes, cardiovascular disease, COPD, obesity, etc.) 

14 

February 22, 2016 
108 

Joseph V. Gu/fo, MD, MBA Written Testimony 

prove clinical utility (as opposed to disease activity as embodied in the effectiveness 

standard), they must be studied in huge trials and either show an improvement in - or 

no deleterious impact on- survival and major adverse cardiac events. And, even at that, 

the FDA requires large and expensive post-approval studies to confirm the findings. 

The FDA has imposed a de facto "better than the Beatles" standard, as well; basically, if 

the drugs are not shown to be more effective or safer than drugs already on the market 

(in large trials using the "average patient standard") the FDA typically denies their 

approval. [This is very unfortunate because often, many patients experience benefit of a 

drug on an individual basis and the effect is lost when patient responses are averaged 

over the entire study population.] So, companies have increasingly foregone the 

development of drugs for these diseases and focused on rare diseases and conditions for 

which no other therapies exist. These qualify for Orphan Drug, Fast Track, BTD, 

Expedited Review, and Accelerated Approval, which provide substantial regulatory 

incentives (reduced review times, smaller trials, etc.). 13 

.. .Add to that the benefit of/ower R&D costs. Derek Fetzer, director, global 

strategic analyticsjglobal strategic marketing & market access, at Janssen 

Pharmaceutical Services, says that this made it worthwhile for a big firm like 

J&J to make a move into the specialty arena: "Improving on the many good 

drugs on the market is a significant, technical challenge," he observes. "This is 

because demonstrating smaller, incremental benefits actually requires more 

patients in c1 clinical study ,from a statistical point of view, and thus is more 

costly." 

Compared to PCP-focused candidates (drugs for use by primary care 

physicians), specialty medicine clinical development can be not only less 

expensive but offer a nearer-term opportunity for cashing-in on an investment. 

Specialtlj medicine candidates typically are vetted by big pharma along the 

dimensions of demonstrating substantial innovation, where R&D efforts can 

require fewer patients and significant differences can be demonstrated over a 

shorter period of time. 

There are regulatory rewards, too. The most prominent "X -factor" in new 

drugs-the FDA-displays more love toward products that aspire to occupy 

salient treatment voids as opposed to those gaining incremental yardage vs. 

existing therapy. Indeed, this is an essential element of FDA's charter. 

"One centra/factor FDA takes into account in determining the speed of review 

of a new product application is whether it addresses an unmet medica/need, 

hence potentially translating into shorter time to market," says Wayne Pines, 

former FDA associate commissioner, who is now president of regulatory 

services and healthcarefor APCO Worldwide. "A usual review is 10 months and 

a fast-track or priority review is six months or less." 

'3 Specialty Pharma: Niches to Riches. Medical Marketing and Media, March 1, 2012. 

15 

February 22, 2016 
109 

Joseph V. Gulfo, MD, MBA Written Testimony 

And, these specialty products are very expensive for two reasons the number of 

patients for which they can be used is small, and there is literally no competition, 

meaning no other drugs approved in these settings. 

Getting the FDA Buck to Safety and FJJectiveness 

Unfortunately, better oversight alone cannot make up for the problems that have been 

caused by many turns of the vicious cycle. Therefore, legislation is necessary to 

essentially re-set the FDA back to the foundations that were established prior to the user 

fee era. This includes: 

1. Restatement of promoting health as the FDA's principal function with respect 

to new products. The law states the following as FDA's mission "to promote 

health by promptly and efficiently reviewing clinical research and taking 

appropriate action on the marketing of regulated products in a timely fashion." 

The law is actually biased toward embracing medical innovation by assuming that 

new drugs that undergo the drug development gauntlet would be approved, 

unless the drugs (or applications) had certain deficiencies. This attitude and 

inclination is not embodied in many FDA regulations and guidance documents, 

as well as in new sections of the law that have been passed as part of 

reauthorization legislation. The law also provides for a balance between preapproval hurdles and post-approval controls and makes clear that approval 

should not be denied in cases where questions about a drug or device could be 

answered in the post-approval setting via post-market controls (studies, 

vigilance, and surveillance). 

2. Restatement of safety and effectiveness as the only requisite standards for 

approval of new prod nets. (For devices, reaffirmation of reasonable assurance of 

safety and effectiveness, and least burdensome approach is needed.) Legislation 

needs to explicitly state that effectiveness is to be evaluated by the FDA in 

accordance with the labeling proposed by the sponsor and that the FDA is not to 

impose standards requiring demonstration of clinical utility for approval. The 

FDA can and should limit the claims based on the data - if there are no clinical 

benefit data in the application, then clinical benefit should not be claimed. 

Likewise, legislation that explicitly lists acceptable measures of effectiveness that 

can support approval- pharmacodynamics effects on disease parameters, clinical 

signs and symptoms, biomarkers, surrogate endpoints, patient-reported data, 

comparative effectiveness, clinical outcomes, and survival. A strong caveat that 

comparative effectiveness, survival, and disease outcomes are not needed to 

demonstrate effectiveness, but are needed to obtain claims that include these 

parameters is needed. The legislation should also state the approved label will 

contain the measures used to determine effectiveness and claims will be limited 

to the specific findings. 

3. Congress can greatly help the FDA by providing for categories of approval 

according to the nature of the data used to provide substantial evidence of 

effectiveness, and if sponsors so desire to obtain additional, 'higher order' 

categories (for example, survival and disease outcomes), supplemental approval 

February 22, 2016 

16 
110 

Joseph V. Gu/fo, MD, MBA Written Testimony 

applications can be submitted. Such a system might lay out four categories of 

approval, as in the following example: 

Category 1. Biomarker-improvement in a biomarker known to be 

elevated or decreased in patients with specific diseases (for example, 

fasting blood glucose, hemoglobin A1c, CEA carcinoembryonic antigen, 

CD4/CD8 ratio, PSA- prostate specific antigen, INR- blood clotting, 

LDL cholesterol, HDL cholesterol, etc.) 

Category 2. Clinical Signs and Symptoms-reduction in pain, 

improvement in activities of daily living, tumor response (size, local 

control, improved progression-free interval); improvement in forced 

expiratory volume; improved walking distance; improved bone mineral 

density; improved treadmill performance and EKG findings (atrial 

fibrillation, pre-mature ventricular contractions), etc. 

Category 3. Disease Modification-reduction in flares of diarrhea, 

reduced joint space narrowing; reduction in MS relapses; reduction in the 

use of other medications (steroids); reduction in development of deep vein 

thrombosis or pulmonary embolism; reduction in sickle cell crises; etc. 

Category 4· Clinical Utility/Outcomes-improvement in survival, 

reduction on major cardiac events (myocardial infarction, heart failure, rehospitalization), etc. 

4. Provisions for Breakthrough Therapy Designation, Accelerated Approval, Fast 

Track, Priority Review and Accelerated Approval should be rescinded -with 

enforcement of the effectiveness standard defined in #2 above and with the FDA 

meeting its review time frames these programs will no longer be needed. [Orphan 

Drug designation and Qualified Infectious Disease Product should remain.] 

s. Post-approval studies should be limited to amassing greater safety databases to 

inform labeling. Studies performed to generate evidence for higher order 

effectiveness claims shall not result in market withdrawal if higher order 

effectiveness objectives are not met. This is in contrast to the current regulations, 

which allow for rescinding product approval if drugs approved on the basis of 

surrogate endpoints (Accelerated Approval) are not shown to have improved 

disease outcomes and survival in post-approval studies. 

6. Personalized medicine in the real world should be fostered, as well. Legislation 

should make clear which decisions are the domain of the FDA (public health) and 

those that are the domain of physicians, patients, and other members of the 

medical marketplace ecosystem (private health). FDA is responsible for safety 

and effectiveness. Clinical utility and clinical benefit often cannot be easily 

measured or analyzed in "average patient studies" because these can vary greatly 

from patient to patient. If sponsors seek claims that communicate clinical utility 

and clinical benefit, then, the sponsor must present data to the FDA that supports 

these claims in a meaningful percentage of patients, even if the exact profile of 

responding patients cannot be defined for labeling purposes, either 

demographically or genetically. Ideally, to further foster personalized medicine, 

the data from clinical trials should be made available to practicing physicians 

17 

February 22, 2016 
111 

.Joseph V. Gu/fo, MD, MBA Written Testimony 

who would then be able to query the databases to obtain knowledge of the effects 

of the drugs on patients given certain demographic and genetic profiles; this will 

aid physicians in their private health decisions. 

Another recommendation is for Congress to refrain from using hearings as a venue to 

publicly embarrass and humiliate the FDA when products that have been approved are 

shown to have undesirable effects and toxicities when used in the real world in larger 

numbers of patients. This initiates the vicious cycle that stifles medical innovation which 

was previously illustrated in Figure 3. 

It also sets an expectation in the eyes of the public for the FDA to be perfect when it 

comes to the review and approval of new products. We should not be conditioned to 

expect perfection, rather, we should be assured that proper mechanisms are in place to 

appropriately judge the safety and effectiveness of new products and to track them and 

rapidly report any issues that might emerge after approval. The FDA should then act, 

appropriately, either with revised labeling or other actions, including removal from the 

market in extreme settings. Congress would do well to reinforce to the public that the 

FDA is just one member of the medical ecosystem physicians, medical societies, 

hospitals, cooperative research groups, drug companies, and clinical researchers have 

an important responsibility to disseminate information quickly and to educate medical 

professionals and the public. Placing blame at the door of the FDA is neither accurate 

nor conducive to fostering medical innovation. 

Conclusion 

As Richard M. Cooper, Food and Drug Administration (FDA) Chief Counsel, said in 

1978, "The perception that agencies are out of control arises from the fact that in being 

called on to make fundamental value judgments they have moved outside their 

accustomed sphere of activity, outside their expertise, and outside the established 

system of controls. This perturbation of the regulatory process will not be corrected until 

the regulatory agencies are relieved of the necessity of making judgments they are not 

equipped to make." The FDA was never intended, and is not equipped, to make value 

decisions for individual patients. These are private health decisions. Congress charged 

the FDA with a public health mandate to approve drugs that arc safe effective for 

physicians to use in the care of their patients, on an individual basis. 

The key to reducing the amount of time required for potentially life-saving and lifeenhancing treatments to reach patients is to restore the FDA to its proper role in the 

medical marketplace, that is, to the role of gatekeeper with regard to the entry of safe 

and effective drugs into the medical armamentarium. It is in the medical ecosystem that 

the diffusion of drugs into practice takes place. The medical marketplace constituents 

(early adopters, medical consortia and societies, hospitals, doctors, payers, and patients) 

decide which safe and effective products are the most beneficial and which should be 

prescribed in widespread fashion. This occurs after using the products in the real world 

for a period oftime; much more is learned about the clinical utility and potential 

benefits in day to day use than is possible during large clinical trials of highly selected 

patient populations. 

18 

February 22, 2016 
112 

Joseph V. Gu/fo, MD, MBA Written Testimony 

Attempts to approve only those drugs that have shown clinical utility in massive 

randomized clinical trials prior to approval serve to deprive patients and physicians of 

safe and effective products that could ultimately be enormously beneficial to them. This 

also runs counter to medical practice, which is as much art as science and requires direct 

first-hand experience with drugs to determine which are most appropriate in the real 

world on an individual basis. Another unintended consequence is that drug developers 

will focus on developing drugs for niche indications that serve small populations where 

clinical benefit is obvious because no other treatments are available. This reduces 

investment and research and development in products aimed at diseases affecting large 

populations of patients. 

Determining safety and effectiveness is a daunting responsibility that should not be 

encumbered with unrealistic expectations- the FDA cannot make perfect public policy 

decisions. Neither is it possible for the FDA to make private health decisions that are 

based on benefit-risk for individual patients. FDA's role is to provide information in the 

labeling - the parameters within which drugs can be administered safely to achieve the 

approved effects -that doctors and patients can usc in their decision-making. 

The FDA is not in it alone despite having been made to feel that it, indeed, is solely 

responsible for health and well-being of the American public. In order to be effective, 

the FDA needs the support, understanding, and confidence of the American public in 

fulfilling their crucial and proper role. 

Attachments: 

The Proper Role of the FDA in the 21'' Century February 2016 

FDA must focus on drug safety and effectiveness, not patients' life outcomes- The Hill, 

February 19, 2016 

Meet FDA critic Joseph Gulfo, the Antonin Scalia of the life sciences Boston Business 

Journal, February 18, 2016 

COMMENTARY: Return FDA to its proper role - Courier Post, February 7, 2016 

Appropriate oversight is needed to change FDA behaviors, not more laws- The Hill, 

December 22, 2015 

MI3 Alert Congressional Oversight ofthc FDA December 1, 2015 

FDA 2014 Approvals- The Message Behind the Numbers- The Hill, January 8, 2015 

GULFO: "Right to Try" just another bandage on a chronic wound- Washington Times, 

July 11, 2014 

19 

February 22, 2016 
113 

The Proper Role of the FDA for the 

21st Century 

Joseph V. Gulfo, Jason Briggeman, and Ethan C. Roberts 

MIJII MERCATUS CENTER 

[trQt] George Mason University 

3434 Washington Olvd., 4th Floor, Arlington, Virginia 22201 

www.mercatus.org 
114 

Joseph V. Gulfo, Jason Bri,~geman, and Ethan C. Roberts. 'The Proper Role of the 

FDA for the 21st Century.'·' 1\1rrcaws Research, J\!Iercatus Center at George Mason University, Arlington, VA, Februar.v )016. 

M3Sif(A( I 

The FDA's mission is to permit safe and effective new drugs, biologics, and 

devices onto the market in an efficient and timely manner. But fear ofbcing 

blamed for tl1e failings of approved products has caused the FDA to become too 

restrictive. The FDA has strayed from d1e safety and effectiveness standards 

that arc set out in the law, instead applying standards for approval d1at arc 

based on predicting the benefits and risks- clinical utility, disease outcomes, 

survival-that an "average patient" will experience. But these outcomes arc 

better evaluated in real-world, post-market settings-that is, in the medical 

marketplace, where knowledge about the value of a drug or device for different types of patients can grow over time. The FDA must return to its role as 

gatekeeper of safe and effective dmgs and devices, and refrain from attempting to anticipate the future judgments of physicians and patients regarding 

benefits and risks. 

JEL code: Hll 

Keywords: Fond and Drug Administration, FDA, medical marketplace, medical ecosystem, FDA regulations, safety and effectiveness. surrogate endpoints, 

clinical outcomes, benefit risk, public health decisions, private health decisions, 

personalized medicine 

Copyright zc; 2016 by Joseph V. Gulfo. Jason Briggeman, Ethan C. Roberts, 

and the Mercatus Center at George Mason University 

Release: February 2016 

The opinions expressed in Mercatus Research arc theauiliors' and do not represent oJ!icial positions oftl1e Mercatus Center or George Mason University. 
115 

T he mission of the Food and Drug Administration (FDA), as stated 

in the Food, Drug and Cosmetic (FD&C) Act, is "to promote health 

by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in 

a timely fashion." This includes "ensuring that ... (B) human and veterinary 

drugs arc safe and effective; (C) there is reasonable assurance of the safety and 

effectiveness of devices intended for human use."' 

Ultimately, the I'D A's mission is to provide doctors in the medical marketplace with access to safe and effective new drugs, biologics, and devices in a 

prompt, efficient, and timely manner. The medical marketplace, which involves 

patients, payers,' and physicians, functions to identify the hest products for 

individual patients. The starting point should be the criteria that doctors, particularly early adopters with the most need for new products in their medical 

armamentarium, minimally demand to see from new products before they ha,·e 

the confidence to start using them. But the FDA is notaskingthe doctors what 

they need; instead, it is trying to encroach on the role of physicians. Why? 

In a word ,fear. This fear stems from unreasonahle expectations of perfection from certain segments of society. Fear ofbeing blamed for the l~1ilings 

of approved products has caused the l'DA to be too cautious in its reviews and 

approvals.' In a sense, the FDA has restated its mission from promoting health 

to protecting health, from permitting new products that can advance health 

to demanding certainty that products will not cause any harm. However, as 

drugs are small molecules designed to have an effect by binding to targets in 

I. See 21 U.S.C. § 393-Food and Dmg Administration (2010) (om· emphases). 

2. P.'l.yers are health in.sunnce companies, :.tccuuntable care urganizations, dosed pruvidernetwnrks 

(e.g., KaiserPem1~mente), Medicare, and su on. 

3. Sec Vahid MonLtzerhodj:Jt and Andrev,- W. Lo. "Is the FDA Too Conservative or T0o Aggressive'? A 

Bayesian Decision Analysis of Clinical Tri::J.lDesign,'' Au~ust 19, 2015, http://papcrs.ssm.com/sol3 

/papers.cfi11?ahstTacLid~26415'17; Ale-x Tabarrok, "Is the FDA Too Conservative or Too Aggressive?," 

1\:farginal Rt>Yolution, Augu.<:t 26,2015, hup://marginalrevolutinn.com/marginakevolution/2015/08 

/is-the-fd::~.-too-cons<:rvativc-or-too-aggressive.ht.J.n.l. 

3 
116 

"\Vhen we 

consider that 

conflicting 

studies continue 

to emerge about 

health outcomes 

related to coffee 

and red wine, 

which h~1ve 

been in use for 

thousands of 

years, we can see 

the absurdity of 

expecting the 

FDA to somehow 

anticipate, 

unerringly, all 

possible health 

outcomes from 

the use or new 

drugs." 

the body, it is impossible to give assurance that no harm 

will ever occur. 

But the expectation from certain areas of society is 

that the FDA completely vets all potential side effects of 

new drugs !or all people in all situations, even effects resulting from uses that arc not intended and are not in conformity with approved labeling. Such an expectation is not just 

impossible to satisfy ·it is entirely unreasonable. When we 

consider that conflicting studies continue to emerge about 

health outcomes related to coffee and red wine, which have 

been in use for thousands of years, we can sec the absurdity 

of expecting the FDA to somehow anticipate, unerringly, all 

possible health outcomes !rom the use of new drugs.' 

Due to fear and pressure from the media, members 

of Congress, and others, the FDA does not take as its starting poinLthe view of doctors who are on the front lines of 

patient care. Instead, over the last 20 years the FDA has 

become markedly more restrictive concerning new drugs, 

in particular through a focus on its efforts to anticipate 

clinical outcomes of drug treatment (as opposed to surrogate or intermediate endpoints, amelioration or red uction of signs and S)1nptoms of disease, biomarkers, etc.). 

The efFectofthe increased restrictiveness verges on telling 

doctors how to treat patients, as though d1e regulators are 

to prescribe drugs remotely from SilverS pring, Maryhmd. 

The FDA is applauueu hy many, particularly those who 

have misinterpreted the rise of an academic movement 

known as evidence-based medicine, when it purports to 

debunk medical practice on the basis of the humongous 

clinical trials that it requires drug companies to perform as 

a condition for approval.5 And so the trend has been for the 

FDA to become more and more restrictive, protracting its 

4. Simple searc-hes of the N::~.tiona11nstitutes ofHealth's Pub;\·Ied research 

d:tl<thase for '·cuft'ee con~umption" (http://wvnv.ncbi.nlm.nihgov/pubmed 

f?Db-puhmed&ternr:cuffeeq~,:wconstm1ptiun) and "n:d wine consumpl.inn'' 

(http://www .nchi.nhTul ihgov/pubmed/?term -:red, wine 'constmlption) 

tum up hundred~ of studies. 

5. \hrthcvl Herper, "Hobert Califf Could Tr.msform the FDA- the Right 

VVay;" Forf.es, September 10, 2015, http://wwv.,·.forbes.com/sites/IThltthew 

herper/2015/09/ltljrobel·t-raliff-conl(l·U\'l.l1Sftwm-the-fd3-the-right-w:ly/. 

4 
117 

pre-approval processes and now frequently requiring that additional controlled 

trials be done after approval." 

As we will show, the FDA is straying, not only from the statutes passed by 

Congress, but also from its own rules, in guidance documents that arc being promulgated; this is how the safety and effectiveness standards have been eroded 

and changed over time. Despite incessant pleas from doctors and patients for 

more products that might help when used appropriately, the FDA continues 

to raise the evidentiary threshold for permitting a new product-recasting 

premarket approval as a venue for the practice of evidence-based medicine. 

This move is aimed at satisfying FDA critics, but it consumes precious time and 

resources, and it dissuades drug developers (and would-be developers) from 

pursuing projects.' 

The FDA has acknowledged the changes in its standards for product 

approval. In a March 10, 2015, opinion piece, two high-ranking FDA oflicials had this to say about the review process: "It is important to remember, 

however, that innovative therapies only save lives if they work properly. U.S. 

citizens rely on the FDA to ensure that the drugs they take arc effective and 

that their benefits outweigh their risks. Improving a patient's life or lifespan 

must be central to the concept of drug innovation."" But the FDA is supposed 

to assure safety and effectiveness of drugs, not life outcomes for patients. A 

drug's label indicates what the drug will have an effect on; safety and effectiveness are to be determined in the context of that labeling. The physician 

and the patient, acting in the medical marketplace, are to determine whether 

and when taking the drug will be conducive to improving a patient's life. 

That we authorize physicians to prescribe drugs off-label is indicative of 

this division of labor.' Certainly, studies of life outcomes can he invaluable 

to informed decision-making by physicians and payers in situations where 

pointed questions have been developed about a drug's benefits and risks 

for patients. But because of the multifactorial nature of disease (the many 

6. Michael Dickson and Jc;m Pmll Gagnon. 

J.nd Development,'' Nature 

7. The FDA has noted in unc guidan<'c 

sents a major componC'nt of d.rug development time and c-n.;;t; the amount rmd n21ture of the evidence 

needed can therefore he an import:mt detl'rminant of1.vhen and whether new therapies become 

available Lo the public." FDA, Guidunce}~}rindustry: ProvidingClinicul Evidewe o[E[_/Ioctivt>r<e:s8f0r 

Hwnan Dru,s.;_and BiologicJl Pn1dw.·t.s, l\.hy 1998, Clinical6.1-2. 

8. Janet \~;oodcock anJ Karen :Vlidth~m. "US Can Continue to Lead in Drug Ilmovation,'' Tlwifill. 

March 10, 2015, http:/ /the hill.com/opin ion/op-C'd/23S2 78-us-can- continue-to-le ad-in-(hug 

-innovation (our empha~is). 

l), Kelli :VIillcr, '·Off-L:J.bel Drug lls": VVhat You I\eed to Know," Wchi\lD Featw·e, .1cc:essed ];muary 10, 

201(1, http://WWtv.webmd.comj::~-fo-z-guidesjfe.'ttun'>/off .. J:lhcl-drug-u~e-tvh:tt-you-need-t0-knG1.v. 

5 
118 

and varied factors that contribute to disease development, progression, and 

response to therapy), it is far harder to produce good knowledge about life 

outcomes for patients than it is to produce good knowledge about a drug's 

safety and effectiveness with respect to specific disease-related parameters. 

The fact that improved life outcomes for the "average patient" arc frequently not proven in trials of drugs that show activity on specific disease 

parameters and arc safe may often have more to do with the multifactorial 

nature of disease than with the drug. Since studies cannot control for all important disease-modulating factors, proof of disease activity and safety should be 

suiTicient for approval; it should not be necessary to show improved life outcomes. For example, it can be shown in a trial that a drug causes dilation of the 

bronchial tubes, but it would be extremely difficult or impossible to prove that 

the drug will improve the lives of a specif1c cohort of asthma patients. Tndeed, 

it is very often the case that even large, lengthy, and expensive outcomes trials produce inconclusive results, so to impose a blanket requirement for such 

lrials-encmnpassing even those drugs \vhuse safety and effectiveness can be 

proven and where tl1ere is an absence of any definite contnwersy~willlead to 

many instances in which useful drugs are needlessly suppressed, causing costs 

and harms to patients. 

The FDA is thus imposing new standards before approval rather than 

allowing the medical marketplace to determine whether and for whom a new 

product is a real innovation. This is directly contradictory to the desires of some 

current legislators, as expressed in the most recent draft oft he 21st Century 

Cures bill, that the FDA consider the individual preferences and experiences of 

patients.10 Different patients experience conditions differently, and are willing 

to accept different levels of risk. An ex ante standard nf improving the life or 

lifespan of an "average patient" cannot take this into account. 

The shift in regulatory philosophy from promoting health to protecting 

health has not only increased the cost and time of drug development, it has 

also moved tl1e FDA !rom its proper role in making public health decisions to 

become an improper force driving private health decisions (see table 1), We 

must change this philosophy in order for medical innovation to deliver on the 

potential tl1at 21st century science ami medicine has to offer, We need to bring 

the FDA into the 21st century by bringing it back to its roots: assuring drug 

sa fcty and efTectivcness, not outcon1es. 

10. H.R.6-21st Century Cures Act, 114th Congress (2015-2016), https://\VWw.congress.gov;bill 

/ll4th*congress./housC'·bill/6. 

6 
119 

TABLE 1. PUBLIC HE-" All H V$ PRIVJ\1 E HEALTH DECISION-MAKING 

MEDICAL KNOWUDCI: IS c,rWWINC AND BEING SHAReD 

l1S NEVH~ BEFORE 

\Ve are firmly entrenched in the information economy. Consumers can go 

online, engage in social media, and ask as many friends and followers as possible about cars, appliances, schools, child care, vacations, lawn mowers, kitchen 

gadgets, and electronics before buying these products and services. Doctors 

can also access unprecedented amounts of data, and they can do so faster than 

ever before. They don't have to wait for the next conference or the next edition 

of a professional journal they can share observations and outcomes instantaneously. Patients benefit because the doctor can combine specific knowledge 

about the individu<tl patient with data on how similar patients responded to 

treatment. The medical marketplace will never be the same. 

Owing to such trends, the future of medicine is at least as exciting as its 

present. Simple software and hardware can turn a smartphone into a device 

that can, mnongothcr things, diagnose ear infections, distinguish a heart attack 

from digestive distress, and identify sleep apnea. Data from Internet searches 

can help the medical community identify previously unknown side efrects of 

medications. These kindsoftechnologicaladvances make it easier to self-diagnose symptoms and to improve monitoring and communication of vital data, 

which brings down medical costs to consumers and leads to safer, more rapid, 

and more cfrcctivc treatment. 

Furthermore, at no other time in history have we been better equipped 

to perform real-world, large-scale outcomes and survival studies with regard 

to medical interventions, such as the use of drugs and devices. There is no way 
120 

that pre-approval studies of drugs and de\'ices, in tightly defined patient populations under scripted medical management protocols, can produce the kind of 

evidence that is available tl1rough real-world data acquisition and the lntcrnet 

of Things. What's more, in the post-approval, real-world setting, data that will 

enhance the selection ofthcrapyfor an individual patient can be made available 

in an unprecedented manner, which can truly drive personalized medicine. 

BUT THE ITli\, PERHAPS Sllf<Pf(ISI~J(~l Y, Hf\S BrCOME 

MOPE f<ESTPICTIVE 

Given the president's 2015 State of the Union address/' which unveiled the 

Precision Medicine lnitiative designed to give doctors a wider range of tools, 

knowledge, and therapies to select from when treating patients, one would 

think tl1at the FDA would embrace the great opportunity represented by the 

information economy. Regrettably, it hasn't. The FDA has in fact moved away 

from personalized medicine, increasing its emphasis on trial results for an 

"average patient" as the standard for permitting new drugs and devices. And 

even though patients, doctors, hospitals. and payers now have ready access to 

knowledge about medical products, the FDA has become more restrictive with 

regard to permitting new drugs and devices. 

In large part, it has done so by moving away from what is written in the 

FD&C Act regarding new applications. This law lists permissible reasons to 

refuse an application. Specifying reasons for refusal implies that approval is the 

default position. The safety and effectiveness criteria found in chapter I of the 

law are the most important: 

(3) The results of the tests show that the drug is unsafe for use 

under the conditions prescribed, recommended, or suggested 

in its proposed Ia he ling or the results do not show that the drug 

product is safe l(Jr use under those conditions .... 

(5) There is a lack of substantial evidence consistingofadequate 

and well-controlled investigations, as defined in 314.126, that 

the drug product will have the effect it purports or is represented to have under the conditions of usc prescribed, recommended, or suggested in its proposed labcling.12 

lL VVhitc House, '·Fact Sheet: President Obama's Precision .1\tledicine Initiative," pressrelcJ.se, 

J.muary 30,2015, https://www.whitehouse.gov/the·prcss:-office/~015/Ul/30/f.J.ct·sheet·president 

·o bam a ·S-precision-medicine· initi:l! ive. 

12. C.F.R Title 21, Chapter l, SuhC"h:~pter D, Part 3H, Suhp.'lrtl).:) 3H.l25. 

8 
121 

Notably absent in the law is any description of refusing an application on the 

basis of the FDA's predictions about how henclit-risk assessments will be 

made by an "average patient" and the patient's physician. The agency has also 

departed from the statutory language by considering possible uses outside of 

the labeled uses. The law states that the FDA is to judge a drug's safety, on the 

basis of"tests" and "investigations:· in the context of the "conditions of use prescribed, recommended, or suggested in its proposed labeling!' This expressly 

does not include possible off-label uses.13 Yet the FDA now asserts thatit"must 

also consider how people will actually usc newly approved drugs once d1ey are 

marketed," using "methods from social and behavioral science" to anticipate 

"cognitive and bcha,~oral be tors affecting human judgment and decision making in the context of health care delivery!'" It is now commonplace for FDA 

guidance documents to stray, not only from the statutes passed by Congress, 

hut also from the FDA's own rules. This is how the safety and effectiveness 

standards have been progressively eroded and changed over time. 

The agency has also become more restrictive by requiring that preapproval clinical trials be far larger than in the past15 --often enrolling participants in numbers comparable to those seen in epidemiological studies of 

post-approval use in the population. The goal of such massive pre-approval 

trials is to obtain data on outcomes (d1at is, whether a patient recovers or lives 

longer, etc.), in order to guess at the clinical utility that a product will have 

once it is in real-world use~even though a predicted lack of clinical utility is 

arguably not a pennissible reason to refuse an application." 

Such outcomes-focused trials, which must he lengthy as well as broad, are 

far more uncertain in their conclusions than are trials that aim to show that a 

drug has biological aclivity related loa disease and is safe to use in that setting." 

§ 3H.125(b)(2) (5). 

Drag Rt",>,:ru/auny De,"ision-Making: Draft 

15. Dickson rmd Gat,'llon, "Key Factors in the Hising Cost." The authors note that data fi:om a vm•iw 

cty of sotu·ccs indicate that tl10 length 1)fd1c proce.ss, from synthesis of a compound to approval of a 

new drug .1pplication, has- increased, and th.'lt thls increase is brgcly due tn llwrc~iscs in H'f.'l..tlatory 

requirements, the length oftTials, and rhe 

16. Surrogate or scales, were used in fe;ver than half of 

the plvotalprema.rkct Lherapeutic: ,Igenl-'> tlL'tt were eventually approved dur· 

ing the period 2005-2012. Sec Nicholas S. Downingd al., "Clinical Trial Evidence Supporting FDA 

Approval of Novel Therapel.ttic Agents, 2005~ 2012," Jmmwf oftheAmeriom ?vfedical Assofiution 3Jl, 

no. 4 (201·1}: 368·-77. Generally !'peaking, comparably S)'Stermtic data arc not or eannot be a~sembled 

regarding drugs that remain unapproved. 

17. Clifton Leaf: ''Do Clinic:d Trials \Vork?," New York Tim('S, July 13, 20I3, http://www.nytimes 

.cum/2013/07/l4/opini•)11/sw1d3.y/do-clinic:ll·tri::~ls-workhtmL 

9 
122 

For example, a cholesterol drug may safely improve cholesterol levels for a given 

patient, but a trial may not show the drug to have positive effects on outcomes 

such as the patient's lifespan. This does not mean, however, that the drug should 

be denied to all patients it could help. Safety and effectiveness are the measures 

that the FDA needs to usc, as per law, in public health decision-making. And 

it isn't just safety and effectiveness·-the question is whether the drug can be 

labeled for safe usc according to the claim submitted. That is, the law in fact 

instructs the FDA to consider new drugs for approval on the basis of the uses 

submitted by sponsors (who are responding to the medical marketplace). The 

FDA should not be telling sponsors that their drugs must showimprovcmentin 

clinical outcomes; rather, the Fl lA's role is to label drugs for safe administration 

in accordance with uses for which they determine the drugs are indeed active. 

It is d1en the job of doctors in the medical marketplace to determine the benefits 

and risks of using new drugs in individual patients, informed by the drug label, 

their experience with the drug, post-approval studies, and patient factors. 

Much of the uncertainty in outcomes-focused trials comes from the 

many assumptions that are made about how real-world settings will differ 

from the controlled trial setting. The FDA's use of such assumptions flattens the real world down to the experience of an imagined "average patient." 

This can mean, of course, that if the "average patient" doesn't surpass certain benchmarks in a trial, the FDA will not permit the drug for use by any 

patient." Yet it is well knuwn that patients often vary dnunaticallyin responsiveness to a given drug, and even though the reasons for such variation are 

often unknown, the responsiveness itself is often readily observable." Therefore, in d1e real world a doctor and patient often have the opportunity to try 

a treaunent, observe that it is not working, and switch the patient to another 

treatment. The availability of additional safe and effective treatment options 

will often improve the results that doctors and patients obtain by using that 

routine trial-and-error process_.," 

18. One useful di~cussion of the FDA's 'average patient'' standm·d is provided in An up Malani, Oliver 

Rcrnbom, and l'vhrk van dcr Laan, ";\c:c:ounting for Heterogeneous Trcam1ent Effects in the FDA 

Approv.:d Process," Fvod dnd Dmg Ldw]ll111Tllll67, no. 1 (2012): 23· 50. 

19. See, e.g., AmlwnyY.li. Lu, ''Dmg-J\fetabolism Hcs.e.1rch Challenges in the :"Je-..v i\!illennium: 

Individual Varirrbility in Drug Therap,>· and Dn~gS:tfety," Dru,1.:;A!etabdism &_ Dispo5itimt26, nu.l2 

(1998): 1217~ 22. 

20. Surh a process-observ;Hion of patient responf;c to treannent, followed by a derision either to 

S'-Vitch or not to switch therapies-is c-ommonly inrorporared in formal modeling of therapy selection. 

For nne ex::tmple, see Daniel CJ..rpenter, Justin Grimmer, ;md Eric Lunuwft~ "Approval Regulation 

and Endogenous Consmner Contldence: Theory .md Analogies to Licensing, Safety, :md Fin:mcia] 

Regubtion,'' Regulation {t Go\•fntd/(c'e-4, no. ·1 (2010): Jf(3-407. 

10 
123 

The FDA sometimes imposes another restrictive 

standard that impedes routine learning processes as well 

as medical innovation in general: the standard requiring 

that a new drug demonstrate superiority over previously 

approved drugs in order to be approved. (lmar,>ine if every 

popular song could only he played on d1e radio if a panel 

of judges declared it "better than the Beatles!"n) An unintended consequence of the imposition of this standard has 

been a relative dearth of novel drugs for major diseases 

that some previously approved products also treat. This 

scenario is an embodiment of the FDA's "protect health" 

mentality, where continuation of the status quo--when 

there are already, say, one or two drugs available to combat 

a given disease--is considered better than a changed sintation, even when the change in question is giving patients 

and physicians access to a drug that is different from existing dru,q:< and comparable in quality. It hardly needs to be 

said that such a drug, when tried, would surely be found 

by some patients to be more tolerable or useful than the 

previously approved alternatil'es. A given drug will not 

cause the same side effects in the same intensity for all 

patients, and so keeping a drug off the market because it is 

not deemed "superior'' in fact does deny many individuals 

access to better drugs the safe and effective options that 

would cause fewer or less intense side effects for them. If 

there were only one birth control pill a\'ailable, a woman 

would not be able to find the pill that works best for her. 

So here is an olwious and frustrating instance of a missed 

opportunity for the PDA to promote health. 

Figure 1 shows the transformation of the FDA 

approval process because of regulators' fear. Safety in 

accordance with labeling becomes safety lor an imagined 

"average patient" with an arbitrarily assigned risk threshold. Effectiveness as identified by activity in modulating 

:n. Credit for the phr.1sc, though 3pplied to consmner decisions as oppost:d 

to re£1.-llatory decisions, goes to.l.1.rk Sc<Jnnell; see "FourRe:l.sons Drugs 

Are Expensive, of Which Two Are False," Forbes, October 13, 2015, http:// 

www.forbes.comjsites/rnatthewherper/2015/10/B/ff)\tr-rea;;:ons-drugs 

-an>expemive-of-which-two-:.lre-falsc/ 

11 

"Imagine if every 

popular song 

could only be 

played on the 

radio if a panel of 

judges declared 

it 'better than the 

Beatles!' '' 
FIGURE 1. FDA REGULATION FOLLOWS PHILOSOPHY 

Congressional mandate to 

promote health 

(Food, Drug and Cosmetic Act) 

A 

safety effectiveness 

+ 

safe when used in 

accordance with 

labeled cond1t1ons and 

instructions 

activity in modulating the 

disease (phamacologic, 

clinical, patient-reported, 

biomarker, surrogate 

endpoints-related) 

Safe and effective products are made available to 

the medical marketplace for real-world use. Drugs 

are vetted and best drugs selected based on realworld clinical utility in individual patients. 

FDA's assumed primary emphasis on 

protecting health 

safety effectiveness 

safety 

determined by 

benefit/risk 

evaluation 

effectiveness • defined by ultimate clinical utility in large 

populations of patients: 

improvement in disease 

modification outcomes and 

survival of the "average patien

Ji 

Epidemiological-scale studies 

determine optimal practice. 

Drug use and disease management are 

dictated to the medical marketplace 
125 

the diseases becomes statistically signiftcant improvements in disease outcomes, requiring very large trials that are all but necessarily longer. 

Finally, FDA talk ofbenefits and risks also creates pressure for comparative effectiveness studies to be brought into the premarket drug approval process. Although "benefit and risk" sounds like a fine construct upon which to 

make determinations about the usefulness of new drugs, it is not (at least for 

the FDA). Rather, it ushers in consideration of a new drug's utility in clinical 

settings, which leads to a demand f(Jr data on h)1Jothetical patient outcomes." 

While clinical trials can show whether a drug is active in modulating disease 

parameters, however, even the largest trials cannot control f(Jr the myriad 

factors that affect ultimate outcomes. In other words, choosing to base FDA 

decisions on benefits and risks implies that the FDA will take on the decision 

roles of physicians and patients, attempting to anticipate or predict their future 

choices. Requiringcomparativeeffectiveness trials is a logical but unfortunate 

consequence of such an attempt because someone must choose among drugs. 

Requiring comparative effectiveness trials further adds to the cost and time 

it takes to develop new drugs. Benefits and risks, and comparative effectiveness, can and should be analyzed post-approval, in the medical marketplace. If 

certain payers demand comparative effectiveness trials, it need not be an FDA 

function to oversee such trials. 

Increased FDA restrictiveness is also manifest in required post-approval 

studies. In years past, required post-approval studies were strictly observational, performed to determine whether a safety signal occurred when populationsofpatients different from those enrolled in the pre-approval clinical trials 

received newly approved products. Now, the FDA is demanding very large and 

costly clinical trials after approval for some drugs, and if a drug does not meet 

the endpoints of these additional trials, it may be taken off the market or its 

labeling may be sig11ific<mtly altered. This amounts to a sort of pharmaceutical double jeopardy, with an attendant chilling effect on investment. Further, 

reasserting the "average patient" standard after some doctors and patients have 

found the drug useful to them and incorporated it into their routines seems 

particularly counterproductive. 

One way to measure the effects of FDA requirements is to look at drug 

development costs. Estimates of total pre-approval costs show that out-of22< The word benefit naturally kads to [he question "to whom?" By contr.:~st, [he wordeJ]Cttivl' natu~ 

rat!y leads one to :1Sk "for wl1:1t?'' Couching the mancr in terms of effectiveness thus tends to prom ott: 

a foc:us on what it is tJut the dmg under study c:m or cannot do, \vhile couching it in terms of benefits 

tends toward speeulative ilnaginings about p.1tient cirtumstances (e<g., constn.tcts sttch as ''the average 

patient") and other unhcn_mlleJ c(m:-;ideratinn ofnutters beyond the re~:•uht<Jr's e"XpelTise and a•van:1wss. 

"'1ERCATUS Cf:NfEP. AT ~:,EOR-GE tvtAS,CN UN!VH1SITY 

13 
126 

pocket expenses have increased at a rate well beyond inflation." This is in part 

due to an increase in the ref,'l.!la tory burden and the greater length and complexity of required trials.'·' Even minor changes in FDA requirements, such as narrowing the window for meeting a trial endpoint, can lead to important changes 

in the pharmaceutical and medical technology sectors:"' 

Observable changes in R&D spending and drug de\·elopment time may 

hint at the problem, but it is likely much larger than this kind of data~or any 

data--can show. A quote by Sergey Brin, cofounder of Google, illustrates the 

impossibility of empirically demonstrating d1e full extent of d1e problem: 

Generally. health is just so heavily regulated. lt's just a painful 

business to be in. It's just not necessarily how I want to spend 

my time. Even though we do have some health projects, and 

we'll be doing that to a certain extent. But I think the regulatory 

burden in the U.S. is so high that I think it would dissuade a lot 

of entrepreneurs." 

Brin has a record of success, yast resources at his disposal, and a network of 

connections, which makes it especially concerning that even he voices such a 

view. If the cofounder of (~oogle perceives the health care sector this way, it is 

probable that there is a significant amount of unseen loss. 

The price that priority review vouchers command is further evidence 

that burdensome regulation has caused harm. Priority re,.~ew Youchers are 

reg11latory inccntiyes awarded to companies that develop drugs for rare pediatric and tropical diseases; upon approval of these orphan drugs, companies 

are awarded a voucher that can he redeemed for priority review of any future 

new drug application, even for drugs that are not intended to treat pediatric 

or tropical diseases. Priority review vouchers are transferrable---they can he 

23. Joseph A. DiMasi, Rom.ld W. Hnnsen, and Henry G. Gr.1bowski, "The Price ofTnnovation: 

~c\v Estim.1tcsofDrug Development Costs," Journ,Il (~(I-I~alth E<:orwm£rs 22, no. 2 (2003): 151·-85. 

Christopher P. Ad.'lms and \'an V. Brantner aLtcmpted to replicate this study. They verified the tlnd~ 

ings and aridcd dut their own estimates varied h·om $SOO million to $2 billion. "Estimating the Cost 

of~ew Drug Development: Is It Really $802 MiUJon?." Health .AJ):Jirs 25, no. 2 (l\'1a.rch 2006): 420·28. 

2·1. Dick:>on and Ga~'TIOn, '·Key Factors in lhe "'""'" 'C"'"· 25. Bruce Boo1l1:md Rodney Zemmel, '·Prospects Rel'iews Drog Dfsi'O\'t'rY ~' 

451-56. The authors note that narrowing the window for meeting an endpoint led 

tiom developing antibi<)tics. 

26. Sergey Brin, interview by Vinod Khosla, "Fireside Chat wiLh Go ogle Co-folmders, Larry Page and 

Sergey Brin," Khosla Ventures, July 3, 2UH, http://W\VtV.khoshventurcs.com/ll.reside·chat-with 

-googl~-i'o-founders- b1Ty-p ~1ge· :md-serge y- brin 

~1ERCATUS CE_NTER .AT 13EORGE t<IASC1N UNIVERSITY 

14 
127 

sold to other companies, and frequently they arc.27 On August 19,2015, United 

Therapeutics announced that it had agreed to sell a priority review voucher to 

AbbVie for $350 million:" Presumably AbbVie believes that a priority review 

will lead to cost reductions that exceed the purchase price of the voucher. The 

expected costs to an entrepreneur of developing a drug or device are clearly 

quite large. Any possible venture that does not involve even larger expected 

benefits will not be pursued~-and there is, o[ course, no systematic data on 

projects that never started." 

WHY HAS THL FD~\ BE COM I:: ~10P[ fi[Sl RICTIVE? 

Fear o[ making a mistake is d1e major driving force of the FDA's mission creep 

and increasingly onerous pre-approval requirements. In !974, l'DA Commissioner Alexander M. Schmidt said, "In all of FDA's history, I am unable to find a 

single instance where a conJ:,>Tcssional connnittee investigated the failure of FDA 

to approve a new drug. But the times when hearings have been held to criticize 

our approval of new drugs have been so frequent that we aren't able to count 

them. The message to FDA staff could not be clearer.""' In subsequent years the 

FDA was sometimes criticized for slow approvals or for reducing innovation, 

but still today the strong perception is that congressional criticism has created 

within the FDA an "underlying motto": "never do what's best, when ylJU can do 

what's safe:' 31 Reviewers, burned li-om the recalls ofVioxx, Meridia, Rezulin, and 

others, have made life easier [or themselves by requiring larger studies focused 

on outcomes and event rates, and even on proving negatives (that a drug doesn't 

cause a particular ellect). They seemingly have decided that d1e best way to avoid 

27. Alexander G3ffney :md Mkhael Mezhcr, "RegubtoryExpbiner: Ever~thing You Need to Know 

about FDA's Priority HevicwVoucb.:J·s," Hcgulatory Affairs Profl::ssionals Society, July 2, 2015, http:// 

www .raps.org;'Regubtory~ Focus/N ews/20 15/0 7/0 2/2172 21'R egulatory-Exp b iner- Everything-You 

• N e cd-to- Kno \\'-A l")()ut -l<'DA ~oE2~{,80S(,99s- Prim·ity-Reviev/-Vouchers/ 

28, United Therapeutics, "United Therapeutics Corporation Agrees to Sc 11 Priority Review Voucher 

to ABBVie for $350 Million,'' press release, Au.._~ust 19,2015. 

29. The lllllrkct price for a priority rcvie"\.V voucher has risen rapidly. In May 2015, Sannfipaid 

$2-iS million to Ren·ophin, mJ in November 2014. Gilead Sciences bought a voucher from Knight 

Ther.1pcut.ic~ !()r $125 milli0n. 

30, ·while Schmidt's oft-l}Uoted ch:tracterizatiun was a slight exaggeration, ell the time nfhis statement it \Vas esscnti::dly :Iceunte. See Daniel Carpenter, Rqmtu.tion and Power: Organi:wtional Image 

and Phanrutcemical Regulation m the FDA (Princeton, I'\J: Princeton University Press, 2010), 337-40, 

especially table 5.6up to 1974. 

31. Tom Coburn, quoted in IIanna Krueger, ''Ex-Sen. Coburn: Congress 'Beats d1c Crap' Out ofFDA," 

The II ill, July 14, 2 UlS. http:/ /thebillcom/policy/he::dthcare/247911-cx~;s.en-<'nbum-c0ngress 

-unflirly-be:lts.-thr-(T~-lp-ntn-of-fi.b 

15 
128 

criticism is to require near certainty before approval. 32 There has been much less 

pressure on them to avoid a different type of error~··the error ofover~caution, 

which leads to more victims of diseases who might have been helped by drugs 

that have been suppressed." Such \~ctims are often bceless and voiceless because 

the public generally cannot know what has been lost due to over-caution. 

A second cause of the FDA's move away from the statute is the increasing influence, starting around l990,ofccrtain strands of an academic movement 

called "evidence-based medicine" (EBM). E\~dence in v:trious forms was of 

course already central in most medical decision-making, and appropriate systematic attention to improved application of evidence is to he cheered." A sophisticated understandingof EHM allows that both researchers' production of guidelines and physicians' individual decision-making are inevitable and necessary, 

that the two must work in tandem, and that e\~dence has relevance to both. For 

example, evidence in the context of physician decision-making can refer to e,;_ 

dcnce about guidelines themselves-fur example, evidence on which guidelines 

to trust, on when to use them, on how lO interpret them, and so forth. 36Butsmne 

have misinterpreted the advent of e~dence-based medicine as representing an 

abrupt paradigm shifl.37 This misinterpretation sometimes manifests itself in 

disparagement of prc-EBM practices in the medical marketplace as bcingrepresentativeo fan unscientific "art of medicine:' In the extreme, the term e,~dencebased medicine has been used pejoratively to insinuate that~-in the currenl EBM 

era-physicians and odlCr care1,<ivers can, and should, have little role in decision 

making. In light of the strength of the EBM movement, it seems reasonable to 

interpret, say, FDA insistence on outcomes studies as an EBM -inspired vote of 

mild to little confidence in physicians and the medic alma rketplace. 

32. Joseph\'. Gulti1, TnnC>\•ati£ln Tfrealrdown: Ffow tht' FDA and Wall Stnet Cripple 1\.f~dical.A.dvances 

(Franklin, T.'\1: Post Hill Press., J014), 239-44. 

33. The distlnction between c:mtiousness and s.1fety is similar to the distinction hcnvecn protecting 

hc.'llth ~md promoting he:-~lth, discus:<;.ed 3bove. On such di1'tinctii)JlS see Aaron I:Vildavsky, Seurching 

for S<Jjet)' (Ne1.\' Rrun:w .. ·ick, N.J: Tr:111S!W1inn Publishers, 1988). 

,H. Jeffr<>y A. Claridge and Timorl1y C. Fabbn, ''History md Development ofEvidence-B~!.<;ed 

~Iedkine,'' Wor!dJoumal (~(Surgery 29 (2005): 547-53. 

35. D.1\'id iv1. Eddy, ''Evidcncc-H:tsed Medicine: A Unifi.cdApprn.1ch," Health ;\.f}:-lirs 24, no. 1 

(January 2005): 9-17. 

36. '·So m:myp:utics have jumped on the EBM band\vagon and so many c:li.nical practice guidelines 

are chumed out by individuals, professional org<.~nizations. insurers, and others that the benetits 

of uniformity may Jis:tppe:Jr in the ctcophony ofovcrbpping, conflicting, and poorly consll'ucted 

t,'l.tidclines. \Nith more tJunl,UOO guidelines created :mnually, c-Jlls for 'guidellnes for cllnical guidelines' have been is:;ucd." Stef:m Tinunt'rmans and Aaron :\huck, "The Promises anJ Pitftlll1' of 

Evidence* Based !\'kdlc-lne,'' I.Te.zlth Aj)Jirs 24, !11).1 ()anu,1ry 200S): 18-28. 

37. Earl P. Steinberg and Bryan R. Luce, ''Evid~;nce B:1scd? CaVt..':lt Emptor!," H~althAjJJirs 2-t, no l 

(Janu:::~.ry 200S)~ 31, l)Jnl 

UNIVERS!TY 

16 
129 

!tis true rl1at certain lines of the EBM literature, such as the evidence on 

geographic variations in medical practice, have pointed strongly to a conclusion 

that the medical marketplace can err, in the sense of falling short of a standard 

or ideal. However, there is also little to no evidence that using the FDA premarket approval process to anticipate adoption decisions is a relatively superior 

approach. 38 Health economists An up Malani and Tomas Philipson have put 

this point very bluntly: 

Economists have conducted relatively little theoretical or 

empirical research on d1e efficiencyofFDA policies. Ironically, 

if a product application were presented to the FDA with the 

scant amount of C\~dence that currently exists on the efliciency 

of the policies ofthe agency itself, such an application would 

likely be rejected on the basis of insufficient e\~dence." 

Their point is only strengthened when one notes thatMalani and Philipson are 

speaking about premarket approval per se, and not necessarily with regard to a 

particularly restrictive variant. 

Jill CATlf<EEPll~ 1\ND Tf![ !vii:DIU\L MAPKUPLAC:E 

Figure 2 shows the FDA's appropriate role as gatekeeper to ilie medical marketplace, which is how it functioned in the 1980s and early 1990s. Regulators 

helped the medica 1 community by approving safe and effective products. Then, 

as described above, physicians, patients, and payers in the medical marketplace 

identified the best products for individual patients through a process not unlike 

natural selection: the drugs mat offered tl1e best clinical results for appropriate 

patients were used preferentially. 

In the 1980s and early 1990s-that is, before the current period of 

increased restrictiveness-the standard used by the FDA in determining 

whether a drug was suilicicntly effective was more about observing the 

drug's pharmacologic activity on a disease, and less about attempting to 

anticipate the drug's clinical utility. Rather than endpoints such as sun·ival 

or fewer bad medical outcomes (e.g., heart attacks, strokes, amputations, or 

38. Jason Briggem:m, Searchingj(y Justffi{_'<Ition of tlw P~)liey of Pre- mJrket _,lppn.mrl oi 

Phurm;:lceuticals, Ph.D. diss., George Mason University, 2015. 

39. Anup Ma!:miand Tomas Philip sun, "The Regulation of Medical Products," in The Oxford 

HanJbook oftheE<:tmomics <.fthe Biopharrn.1cewioJi Industry, ed. PatTicia ::\1. Danzon :m~t Sean 

~ khol..;;on (tJxford, l K: Oxford l !niversity IJre~s, 1011), 101. 

17 
I IG\ tRE 2 THE MEDI(;\L IN THE l'::!8('s ANO EARLY 1990:; 

FDA 

early adopter phys1c1ans 

cooperative groups and 

drug companies 

widespread use 

Approve safe and effective products for 

med1cal armamentanum. 

IdentifY product uses that y1eld good results and 

low tox1c1ty, and share best practices. 

Publish data, discuss results, and rev1se disease 

management algorithms. 

Inform package insert rev1sion or, if toxicities emerge, 

market withdrawal/black box warning. 

Use products appropnately for improved health. 
131 

progression of disease), trials routinely used surrogate 

and intermediate endpoints (e.g., fasting glucose levels, 

blond pressure, tumor shrinkage, and stress tests).40 

How was clinical utility assured? It flowed out of 

the medical marketplace. The FDA of the 1980s ami early 

1990s knew its place in the medical ecosystem to be that of 

a gatekeeper of new products entering the medical armamentarium. The FDA's role was to permit drugs, biologics, 

and devices based on safety and efficacy (reaS<)Ilahle assurance of safety and effectiveness for medical devices), and 

then the medical marketplace would adopt the best treatments from among those permitted by the FDA, for usc by 

individual patients. The 1rgencywas at the top ofthe funnel, 

making sure that only safe and effective products passed 

through. As they still are today, doctors were assigned 

responsibility for authorizing nnd guiding pnticnt usc of 

prescription-only drugs, and also as they are today, doctors 

were empowered and expected to prescribe drugs off-label 

when appropriate:" 

How were decisions to adopt drugs made? How was 

personalized medicine exercised? Mostly, such decisions 

were based on real-world experiences of doctors treating 

patients and by additional clinicnJ trials sponsored by cooperative clinical groups (e.g., National Institutes of Health), 

hospital networks, <md the biopharmaceutical and meJ tech 

industry. This infornwtion would he shared at medical 

meetings and in the literature. Doctors who observed B 

patient experiencing an idiosyncratic adverse response 

would switch that patient to an alternative treatment." 

In a natural selection process, doctors and patients would 

learn the best treatment for individual medical situations 

40. Russell Katz, '"Bionurkers and Snrrog;lte l\hrkers: An FDA 

Perspective," Journal t~(thc Ameril,m Society for NcuroTherJpewics 1, no. 2 

(April2004): 189-95, Joi: 10.1602/ncururx.L2.189. 

41. Alexander T. Taba.rrnk, ''t-hsessing: the FDA via the A.nunnly of Off~ 

Label Dmg Prescribing,'' Independent ReviewS, no.l (Summer .2000): 

25--53. 

42. G. H.. Venning, "V:tlidity of Anecdotal Reports of Suspected Adverse 

DrugReaclions: The Problem of False Alam1s," JJritish Jl!fedical Journul284 

(1982): 2•1'1--52. 

19 

"The FDA of 

the 1980s and 

early 1990s 

knew its place 

in the medical 

ecosystem to 

be that of a 

gatekeeper of lJe\\ 

products entering 

the medical 

armamen tclri um .'' 
132 

and use the appropriate drugs and devices in the medical armamentarium. This 

narrowed the funnel by identifying optimal uses of available safe and effective 

products. More often than not, these pearls of wisdom, even as they were codified in practice guidelines <md medical pathways, would never make it into the 

package insert (that is, the labeling approved by the FDA). The abilityoftoday's 

medical marketplace to vet approved products and drive the adoption of those 

that have the greatest clinical utility is greatly strengthened by the emergence of 

online patient and doctor communities for immediate sharingofknowledge and 

best practices. The FDA itself has acknowledged the power of the lnternet by 

partncringwith Google to usc search terms and topics as a meansofidentifying 

new information ahout drugs:n 

We believe that a reinvigorated medical marketplace system, with the 

FDA returned to its proper role at the top of the funnel, could help realize the 

promise of the information economy and personalized medicine for 2015 and 

beyond. FDA pre market approval is designed to deliver an initial permission 

decision; posunarkct controls are aimed at modifying drug labels, or even withdrawing the drugs, if issues emerge in their use in the medical marketplace. 

Adoption decisions do, and should, Yaryover time as more is learned in clinical 

practice, additional trials, and epidemiological research. \\'ith knowledge so 

much more readily available to doctors, drugs should again he permitted on 

the basis of safety and effectiveness-and not rejected on the pretense that, by 

invoking a mythical "average patient," the FDA can credibly wrap all future 

adoption decisions into its permission decision. Prescription requirements 

remain a viable means of restricting patients' access to drugs that are ditlicult 

to use appropriately and as directed. 

Figure 3 shows the FDA at the Lop of the new and more dynamic medical 

marketplace, in its proper role of permitting safe and effective drugs onto the 

market. It also shows how the information economy and the ability to rapidly 

share and process data help doctors improve patient outcomes at a rate and 

scope previously not possible. The new marketplace better assures that appropriate treatments arc pro>~ded to patients. 

43. Michael Mezher, "FDA and Google Talk 'Adverse Event Trending-,'·''TI.egtllatory Affairs 

Professional Society, July 16,2015, http://\VWW.rlps.org/H.egub.tory-Fo('us/Ne\vs/2015/U7 /16/22888 

/FDA· and-Googk-Talk-Ad verse-Ewnt-Trending/ tJ. 

!">1ERCATUS (f.Nf£R t,f (it.OP.GE HASPN UNIVERSITY 

20 
f- !GUf-/L ) THE-. ME:DICAL HARKE:_ TPLACE AS r! SHOULD BE TODAY 

FDA 

early adopter physrcians 

physicians and patrents 

payers, patrent advocacy 

and cooperative groups, and 

drug companies 

Internet of Things 

Widespread use 

n£-v<l dmgs, biologics. devices 

Approve safe and effective products 

Identify product uses that yield good results and low toxicity, 

and share best practices among clinioans 

Use online profess1ona! and soc1a! networks to share expenences V..'lt

new products and how to achieve good results 

Conduct additional use studies (including studies of different !X)pulatio

publish data, discuss results, and revise disease management algorithm

Inform package tnsert reviSIOn or market withdrawal/blackbox warnin

Gather data, enable rapid data querying for truly personalized medicin

and make genomic profiling routme 

Use products appropnate!y for best possible outcomes 
134 

fiE/\ SONS TO I<Ei~WIGOf<ATE 11-IL fWLI:". ()F 1 ilE 

r•lEDICAL ~-lARKETPLACL 

Why should we go "back to the future" in this way? Why will this system be 

better? We believe an important element of the answer is that doctors believe 

it will help patients. And, patients want their doctors to try to help them morethat is what Right to Try laws, approved now in 21 states, are all about. 

PhysiCiclllS clnd l·'iltl•'llh Should HcWP More Option;, ~·lute> Ouickly 

\Vhat do early adopters want to sec from the FDA approval process before they 

start the real-world use of drugs, knowing that drug studies do not directly correlate with individual patient experiences? 

I, They want products that have been evaluated in a manner that gives them 

confidence to prescribe drugs safely and in accordance with appropriately 

labeled conditions of use and instructions. In addition, they want to see 

data demonstrating that new compounds have activity in clinical parameters ofimportance to them and to their patients. Statistically significant 

assessments of safety, as well as data supporting the pharmacologic activity of new drugs (sltrrogatc markers, intermediate endpoints, symptom 

relief, resolution or improvement of clinical sit,'ltS of disease) are required 

prior to use by early adopters. Defmitive evidence of improvement in discase outcomes and survival is not required. 

2. There has hel'n :m inexorable progression toward greater and greater data 

demands by the FDA before approvaL This greatly impedes the development of products for diseases that alrect large segments of the population 

in filVor of niche diseases, hurts patients by delaying products that can 

provide medical benefit, and adds to the time and cost of trials. Doctors 

need more drugs to treat diseases that affect millions of Americans. 

3. Unfortunately, today's FDA often requires unequivocal evidence of clinical utility to be demonstrated before approvaL vVhile the doctors are in 

support of having as much data as possible to inform their treatment decisions, there is no doubt that some doctors feel that post-approval studies pcrfi1rmed hy industry, as well as independent clinical investigators, 

are well-suited for prmiding evidence of clinical benefit. Moreover, they 

want to see clinical benefit for themselves, or they will not continue to 

use the drugs. 

'L There are many exampl~s of th~ FDA having denied approval, or having inhibited further development, of drugs that would make valuable 

'JHIVERSIT'/ 

22 
135 

additions to the current medical armamentarium. Doctors want more 

safe and effective products that can help their patients. 

Table 2 shows the minimum amount of information physicians need for 

several medical conditions in order to make choices with their patients, both 

immediately after the release of new drugs and after the drugs have been in the 

medical marketplace for a while. In summary, before using new drugs, doctors 

who are early adopters want to know that drugs can be safely administered, have 

pharmacologic activity, and, in some cases, have shown a hint or trend (rather 

than statistically significant proof derived from epidemiologic-scale studies) of 

improving disease outcome parameters. Dcfinitiw proof of clinical utility and 

outcomes or sun~val before approval is not necessary and unduly delays or holds 

back important new medicines that doctors want to use in some of d1eir patients. 

The appendix contains additional discussion about the medical conditions and 

the development efforts of drugs to treat the diseases highlighted in the table. 

Tile FDt1's Exp<'~nciHI F<oltc flds Cr•:''lted l:conurnic Problems 

Economic analysis can shed light on unintended consequences of the FDA's 

increasing restrictiyeness and imposition of an outcomes-focused standard. 

Here we focus on two growing problems, both of which can be addressed by a 

reinvigoration of the medical marketplace model. 

tncrcsas0d r(~sltlct_lv,.:>i"l<:~ss i;as cJt::tiiiCd [XltH?i1ts uood Jlt~>rnatJVt:'S to ·J!dE'I 

clruqs. There are many drugs in the current armamentarium that were 

approved hack when there were smaller and much less rigorous trials. The 

FDA keeps these on the market (generally appropriately), while often refusing to approve drugs that are being developed in to day's world, with today's 

biomarkers and assessments. and today's brand of transparent rigorous trials. 

We should, all else being equal, probably favor drugs that were developed 

more recently even if they demonstrate only comparable safety and effectiveness, rather than superior performance. Drugs developed in recent times have 

been characterized to a much greater extent (commensurate with discoveries 

and advances in basic biology, laboratory methods, genomics, and medicine) 

compared to drugs developed 15 to 30 years ago. However, by supplanting 

safety with benefit-risk and ~tfectiveness with clinical utility and outcomes, 

the FDA has moved the goalposts, with the ironic result that older drugs have 

been protected from newer would-have-been competitors, even in instances 

when the clinical usefulness of the older drugs has faded. 

MER(ALJS CE~'>!TER AT 1::iEOqGE MA.S0N UNh/ER5!TY 

23 
TABLE L MINIMUM INFORMATION PHYSICIANS NEED TO MAKE DRUG CHOICES 

r {/>e FDA ottenreqU!rescardirriJSCUI.¥ outcrvr>es~reductron!fl myrxiHUJa! 

;nt¥CI/Of1. stroke etc ~~to be 1!11tl¥edascxJfldJf/Of!SD! approval) 

: ihe FO/', oflcorcQuJre!, a redud,on !nfrequenc{ of ma;orc;)(dtac events/ 

( T,'"fe FDA ofienrec;wrescard!nvil'itular outw:nes~Jeduct!on !!l myoearofaf 

mf;ycuon. :make e!c. ""iJSCIJflditmnsof app•ova.l) 

( Tf>e FDA reqwres reductron ill unc and m Pdllems Wltfl gout.v <Htlw;t;s as me 

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l r!J<?FDA oflenreqwres flgbAic rer.itXf.lCJI"~'> an(j/argeoutcomes stuOJCS tu 

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"The reason 

the FDA had 

approved no other 

oral drugs to 

treat methicillinresistant SSSI \vas 

largely that it h<ld 

been requiring 

superiority to 

active treatment 

as the criterion for 

approval, which 

is very ditl1cult to 

demonstrate." 

The antibiotics crisis a host of health problems 

caused by emerging bacteria that resist treatment by 

approved antibiotics~ is a prime exarnple~44 ZyvoX"" (linczolid), an antibiotic granted approval by the FDA in 2000, 

was "the only oral drug approved for complicated SSSI 

(skin and skin structure infections) caused by methicillinresistant Staphylococcus aureus (MRSA)" until 2014. The 

reason the FDA had approved no other oral drugs to treat 

methicillin-resistant SSSI was largely that it had been 

requiring superiority to active treatment as the criterion 

for approval, which is very difftcult to demonstrate. (Further, it is unethical to force patients into a treatment to 

which they are knowingly resistant for the sake of a clinical trial -that is, a treatment that is certain to provide no 

benefit to them- in order to show superiority, a situation 

that can often complicate clinical trials.) 

To address these issues, the Qualified Infectious 

Disease Product (QDIP) designation program, passed as 

part of the 2012 Prescription Drug User Fee Act (PDUFA) 

reauthorization (FDA Safety and Innovation Act), allowed 

for fast track approval of antibiotics for serious or lifethreatening infections, including those caused by an 

antibacterial- or antifungal-resistant pathogen, which 

permitted the demonstration of non-inferiority~~ rather 

than superiority~~~ to active treatment as the endpoint for 

clinical trials to support approval. Following this, Sivextro" (tedizolid) was approved in 2014 by demonstrating 

non-inferiority to linczolid. Unfortunately, outbreaks of 

linezolid -resistant strains ofStaphylococws au reus had by 

then been occurring for several years." In general, over 

14. See, e.g., Fnmrc;c; ·weaver, ''The Antibiotics Crisis,'' The Week, 

November 1f:., 2U13, hup://theweek.com/articles/4563.J-O/antibiotirs~crisis. 

45. Pllzer, HighLight:<. of Prescribing Information: Zyvox, last modified July 

2015, http:/ /labcling.p flzer.com/Show L aheling.aspxfid-64 9. 

46. :'vlerck,Highlights of Prescribing Infrnmation: Sivextro.la~! modified 

July 2015, http:/ ;w~nv .merck .comjproduct/usa/pL circul:u·s/s/sivexu·o 

/sivcxtro_"pi.pdf. 

'!7. Philippe Prokoc:imer ct ,'ll., '·Tetlizolid Phosphate vs I.inezolid for 

Treatment of Acute Bacterial Skin and Skin Structure Infections.'' Journal 

tlfthe r1mcn'can Medital Assodati,..1n 309, no. 6 (20 l3): S59-6Q. 

!...1ER(A1 CEP.ITER ,~.I GEO={Gr ~IASCN UNIVERSIT\' 

26 
139 

this period the problem of antibiotic resistance had continued to grow while 

the flow of new antibiotics diminished. 

rhe ·av~·r,::~Jf) pr=ltl~lnt" ~t:Jncl~Hd IS drsf~vorVIQ drU~JS for L.11\Jt~·populat!On ellSThe "ayeragc patient" standard as applied in outcomes-focused trials 

has caused a burgeoning of narrow, niche claims:" Once the domain, rightfully 

and appropriately, of rare pediatric diseases such as enzyme deficiencies, targeting narrow diseases is now a preferred deYelopment pathway for eyen the 

largest companies because of the FDA's implicit and explicit incentives, such 

as priority review youchers, Breakthrough Therapy designation, Fast Track 

review, and Accelerated Approval. 

Could these incentiyes cause companies to abandon pursuit of drugs to treat 

diabetes, heart failure, obesity, chronic obstructive pulmonary disease, addiction, 

early-stage cancer, and other diseases with massiye numbers of patients? For 

claims of effectiveness in those diseases, the FDA may require clinical trials with 

tens of thousands of patients, assessing not only disease outcomes but also survival'' Meanwhile, fi:>r narrow. niche claims---which are often created by simply 

taking refractory (disease recurrence despite prior treatment) populations or 

those with a sped fie mutation --the FDA requires comparadvclyvery little in the 

way of testing. Not only arc required trials smaller and thus less costly for niche 

drugs, there is also a lower bar for approval. Recall that -unfortunately -the FDA 

often considers "the benefits and risks of other available therapies'' when making 

approval decisions on new drugs."'' But a maker developing a niche drug, where 

there are no available therapies, doesn't have to worry about the FDA attempting to estimate the drug's value compared to existing drugs. Furthermore, tbe 

speciftcily of a niche drug assures its good performance in an "average patient," 

and there is a limited number of patients that would be exposed should tbedrug 

turn out to he more toxic than originally thought. For all these reasons, the final 

decision to approve a niche drug is often a no-hrainer.51 The FDA loves to tout 

48. Joseph V. Gulfo, 

Rt~port, Arrtl27, 

-orphan-drug-def'ignation-\V3rps-mcdic:-t!-rcscarch. 

49. See, e.g., .\ialorye Allison, "Can Cancer Clinical Trial" Be Fixed?,'' N.1t!./.rt' BioteclmohlR,..Y 29 (2011): 

13-15. 

The FDA uses rev,:a.n.b such 

:1s prioriryrevie·w vouchers [Jnd extendedperiuds ofm .. 'lrket exclusivity to induce makers to develop 

dtugs for rare diseases. The Breakthrough Therapy designation, made law in 2012, provides regubtory incentive for developer.::. to pursue drugs tlut address signific:,mt unmet medical needs, including niche, refractorycbims. And there .1re new incentives fur niche product devt.:lopment in the 21st 

Century Cures bill. 

27 
140 

niche-drug approvals and wants them to weigh heavily in evaluations of FDA 

performance (i.e., PDUFA)-and Congress has generally let d1c FDA get away 

withit.51 

The FDA Shottld P,lY lll•E•d to tlw Sptrit ot tlw LilW 

We believe that the system of the 1980s and early 1990s was more in keeping 

with the law than is the more restrictive regime the FDA now imposes. Back 

then, Congress limited FDA consideration of a drug's effectiveness to the effect 

represented on the proposed labeling. 53 Congress intended drug developers to 

conduct clinical trials and submit applications for uses of their products that 

they see ftt, assuming that market forces would drh·e the selection of meaningful and appropriate endpoints in order Ji)r their products to compete. Drugs 

were meant to be sakwhen used as labeled, and to have some activity in modulating a tmgeted clinical parameter. FDA approval was not to be interpreted as 

meaning that a drug could be supposed risk-free for an "average patient" or as 

meaning that a drug's etlicacy had been measured relative to other drugs.5

'' nut 

in practice, it is the FDA that tells companies what is and is not appropriate 

evidence, and today's FDA has moved away from pharmacodynamics acth;ty, 

surrogate markers, and intermediate endpoints to survival and major health 

outcomes. Companies have no choice but to listen. 

The increased sophistication and etliciency of today's medical marketplace in carrying forward a natural selection process to arrive at the best products for appropriate patients should give us confidence in reasserting d1e spirit 

of the law as described above. In particular, the capability and importance of 

payers in assessing medical value has grown enormously. Payers have a very 

strong incentive to select from among the safe and effective products those 

that arc of the greatest medical value--that is, the ones that provide health 

52. If FDA revinv perfom1anr-e were meeting goal-. setout in the Ll.w-such !lS the go.1l oflO months 

for a st.111cbrd new dru_g- :tpplic:J.tion revic\v-- some niche~drug t:xdusivity incentives (,~ee previous 

note) could be reduced or dropped. But f;.)r t:ruc orphnn diseases, c .g., congenital enzyme ddlcicncics, 

exclusivity inducements \vill still he tKcckd. 

53. C.F.R. Title 21, Chapter 1. Subchapter D, P:ut 314, Suhp:m. D.§ JH.l25(b)(5) . 

.:'1<1. Another important benefit fromrettm1ing to more tightly defined standards for safety and e!Tec~ 

tiveness would he enhanced precision oftl1.e informatiun~dfunctiun served by an FDA approval decision. That is to :-ay, the meaning of ~m appruv:~l--whata drug's approv~1l by the FDA so.~ys (:md dues 

not say) alx>ut the drug-hns be~n muddled hy the greater uncert:tinty inherent in outcomes-focused 

trials and the application nfthe "average patient" c-oncept. On the import:mcc of public understandingot' the meaning of a dmg's approval b~r the FDA, see Lisa M. Schwartz md SteYen \Voloshin, 

.-'Communic:1ting l'nc('rrainties about Pre:-cription Drugs to the Public: A N:ttion.ll R:mdomized 

Trial,'' .A.rchil·cs oflnu·m.zl.ilt'dic'ine 171, no. lf, C:~Oll): 14(,3-68. 

MERC..:'J·JS CE\:TER 

28 
141 

outcomes that are satisfactory to physicians and patients. Large payers, particularly Centers for Medicare and Medicaid Services, often demand -and sometimes sponsor post-approval studies that provide evidence on outcomes, 

which give assurance to late adopters or cause early adopters to reconsider. 

Furthermore, a marketplace with multiple payers tends to mitigate negative 

impact from any idiosyncratic obstinacy on the part of the regulator. When 

there are multiple payers, there are multiple opportunities for innovative 

products to be studied and appreciated, and then later more widely adopted, 

perhaps even by a stubbornly closed-minded payer once others have validated 

the value of the intervention. A similar dynamic, of course, applies with regard 

to physicians: early adopters use the products first, and then late adopters may 

or may not follow. 

CONCLUSION: CONl~f~ESS SHOULD ACT TO DEFINE mA 

STANDARDS f=OP Sf'I.FETY /\ND EHECTIVENESS 

The good news is that the fix for mission creep is quite easy: Congress can guide 

the FDA back to the letter and spirit of the FD&C Act by more explicitly defining safety and eifectivenC'ss. Doing so can prevent the FDA from dictating to the 

medical marketplace how new drugs, biolo).,>ics, and devices should be used to 

help individual patients. There are several steps Congress can take to put the 

I"D A back in its proper role: 

1. Explicitly limit the FDA to considering the safety of intended uses, according to the label. FDA reviews should not be permitted to speculate about 

the safetyofoff-labeluses or of uses in populations beyond those the label 

indicates. 

2. Define safety with regard to the likelihood of causing death, debilitation, 

or severe harm. This definition would focus FDA reviewers on filtering out the most dangerous drugs and allow the medical marketplace to 

determine appropriate uses for medicines that might be blocked under a 

more restrictive safety threshold. Such adC'finition is aligned with the fact 

that individuals experience conditions differently, and it places the focus 

on whether the drug can be labeled in such a way as to promote its saft' 

administration, in accordance with the law. 

3. Define effectiveness as having posi tiveactivity on the disease (amelioration 

or reduction nf signs and S}1nptmns, surrogate endpoints, biomarkers, etc.). 

4. Hequire the FDA to expand its use of surrogate endpoints (including biomarkers) in trials and reviews. This should include specific, actionable 

29 
142 

targets so that the FDA can be held accountable by the public if it fails to 

take action. 

Congress should couple these reforms to the law with a strengthened 

norm against undue criticism of the FDA by Congress. Risk cannot be eradicated from the usc of drugs, and human foresight is limited; therefore poor 

outcomes cannot by themselves justify the placing ofblame for those outcomes 

upon d1e FDA. Whenever d1e FDA is assiduous in following the law and acting 

appropriately on the knowledge available at the time, then it is to be supported. 

Congressional leaders should vocally aflirm such a norm in order to reduce the 

fear that has led the Fl )I\ to a stance of excessive cautiousness and protraction. 

The FDA has an integral role in the medical marketplace as arbiter of 

appropriately defined safety and effectiveness, but the FDA's judgment with 

respect to safety and effectiveness clearly has gone awry. Congress must act to 

address this so dnt the other constituents of the ecosystem can perform their 

roles in order to ensure that the best products for each individual patient arc 

used in a manner Lhat will enhance the health of all Americans in a prompt, 

efficient, and timely fashion. 

i'-1ERCATUS(t 1

'-ITER 1:JEORGE f"LASCN UN!VER$rfY 

30 
143 

APPENDIX 

EXAMPLES UF Til[ lr·1PfWPEP I~OL.E OF THE FDA IN DRUG 

DEVELOPMENT liND PEVIEWS OF N[W DRLJC) .APPLICATIONS 

The FDA's efforts tn dictate to the practice of medicine and to supplant the 

medical marketplace in determining the most appropriate usc of drugs for individual patients are very apparent in the development requirements it imposes 

on drug companies and the labeling restTictions it places on new products. This 

section highlights recent examples in which safety and effectiveness were not 

the primary focus of the Ffli\. In these examples, the FDA assumed the role of 

the medical marketplace by demanding data on clinical utility, clinical benefit, 

and disease outcomes as conditions of approval. 

Hypercholc'sterolem i,1 

Hypercholesterolemia is a particularly interesting example because it demonstrates the FDA's approach to surrogate markers, the use of which it does not 

support as the basis of product approvals in other than narrow or niche disease 

populations. 

The finding that LDL cholesterol reduction leads to improved survival 

has been shown in numerous landmark studies of several different drugs (e.g, 

pravastatin, atorvastatin, rosuvastatin) over d1e last 20 years. Why must new 

drugs to reduce cholesterol he made to show improved survival? With all of 

the studies that have been performed on multiple different compounds, ifLDL 

lowering is not a good surrogate for cardiovascular outcome, the concept of 

surrogate endpoints is hollow. 

At the June 2015 FDA Advisory Committee meetings for evolncumab 

(Repatha by Amgen) and alirocumab (Praluentby Sanofi and Regeneron), both 

monoclonal antibodies directed against a new target in cholesterol synthesis, 

impressive data demonstrating dramatic LDL reductions were reviewed. The 

FDA approved the products on the basis ofLDL lowering for very high-risk 

patients, hut is withholding approval for broader patient populations until the 

studies on survival and cardiovascular outcomes (major cardiovascular events, 

abbreviated MACE) are completed and positive. Many in dJC medical community are not in support of withholding that approval: 

"I was really focused on the very large unmet medical need in 

patients who arc high risk," said panel member Dr Philip Sager 

(Stanford University School ofMedicine, San Francisco, CA) in 

explaining his "yes" vote. "It's mDre likely than not this drug 

31 
144 

will actually he able to reduce cardiovascular outcomes. I do 

acknowledge the uncertainty in not knowing what the cardiovascular outcomes will actually show, but r was unwilling to 

wait until2017 or 2018 to get those results!'" 

Michael!!. Da,~dson, MD, FACC,FNLA, professor and director 

of the lipid clinic at the University of Chicago Pritzker School 

of Medicine, said more populations should have been recommended for immediate indication."! was disappointed that the 

panel did not recommend approval for statin intolerance, which 

is ditlicult to define, but from a patient perspective is dearly a 

real issue;· he said. "The FDA panel vote is a sober reminder 

that there are many skeptics who want outcome trials he fore 

utilizing these very effective and well-tolerated agcnts."'6 

The European Commission approved Amgen's Repatha (e,·olocumab) to 

treat patients with uncontrolled cholesterol who need intensive low-density 

lipoprotein cholesterol reduction, which indudes stalin-illlolerant patients." 

The FDA approved Praluent and Repatha only for patients with cardiovascular 

disease who need more help getting their cholesterol under control, including 

sufferers of a rare genetic disorder called familial hypercholesterolemia, hut 

didn't indicate Praluent and Repatha for statin-intolerant patients." 

Heart disease is the leading cause of death in the United States. One 

would think that the FDA would want to get as many safe and efl'ective drugs 

on the market as possible in order to reduce the number of deaths due to heart 

disease. However, rather than accepting proof that a drug reduces LDL, the 

FDA withholds appnwal for the general population until drug makers have 

conducted longer and more expensive studies. As any student of Economics 

55. Michael O'Hionbn, 'Approve PCSK9 Tnhihitnr F.v(lloc-um:-J.b, FDA Panel Recommend:;,'' 

1\Jcdscapc.com, June 10, 201:1, http://wv,.'l.v.medsC'npe.comjviNvnrticlc/S'l6236. 

56. Erik S\vain :md Adam Taliercio, "'FDA Advisory P:l.11t>l Backs Approval ofPCSl\9 Inhibitors,'' 

Cardioiog:.· Today, July 2015, htt p:j/wwv..·.healio.comjcardio logy/chd-prcvcntion/n C\vs/print 

inEU." 

58. FDA, "FDA Approves Pr.1luent to Treat Cert.'l.in Patients with High Cholesterol: First in a ~ev,.r 

Chss oflnject.:tble Cholesterol-Lowering Drugs," news release, July 24, 2015, http://www.ida.gov 

/NewsEventsjNe\\'sronm/Pre:->sr\nnuw1c:ements/urm455883.hlm: FDA, "FDA Approves Repatha to 

Treat Certain Patients \vith HighCholesteroV' news release, August 27, 2015, http:/Jwww.fda.gov 

/N cwsE vcnts/N e\vsroom;'Pre<;sA.nnoun renlt'll ts/urm4fJOOR2. hb11. 

32 
145 

101 knows, increasing costs leads to less of a given action. Increase the costs 

to drug makers of marketing cholesterol drugs, and they will make fewer cholesterol drugs. 

Cotrt!r:tlml nt Mcti1hollc Dr,r,lll()f'il!''lits 

Metabolic derangements are medical conditions manifested in abnormal laboratory tests, initially, which if untreated can lead to clinical manifestations, 

such as cardiovascular disease or diabetes. While doctors arc often appropriately loath to "treat lab tests;' intervening to normalize grossly abnormal 

laboratory parameters is good medicine in most circumstances. It seems clear, 

however, that the FDA will not approve drugs based on their effects on these 

laboratory endpoints alone. Metabolic derangements include correction of 

serum uric acid, triglyceride, HDL cholesterol, and glucose abnormalities.'' 

Most diseases are quite complex, so it is extraordinarily dillicult to conduct 

trials that, amid the multiple factors that simply cannot be controllPd, can 

ferret out clinical benefits resulting from the correction of derangements. So 

when clinical benefit is made d1e standard for approval, doctors and patients 

are denied access to compounds that both correct derangements and are safe 

when used as labeled. Following are two examples of these conditions and 

drugs that treat them. 

HypHlriqlycHidemti1 

\\'hen Amarin Pharmaceuticals sought to obtain approval l(Jr use ofVascepa 

in patients with elevated triglyceride levels (above 200 mg/dL), the FDA 

required the company to perform a study demonstrating significant triglyceride lowering and to recruit at least half the patients in a cardiovascular outcomes stucly(rt'duction in MACE, inclttdingmyocardial inf:1rction, stroke, ~md 

death).'" The company filed a new drug application in compliance with the 

directive frorn the FDA, but the FDA then expanded the requirements, stating 

that it now wanted to see the results of the outcomes study as a condition of 

59. Joel Schiffcnbauer, "GoUl: Clinical Hcview and Trial De~ign Issue~" (presented al the FDA 

Arthri1 is Advisory Cm1Unit1c~.;, June 

.ppt .,.&c:d -'02&-hl-:en&-ct-c-lnk&gl-us. 

60. Triglycerides are a type of fat and excessive levels are associated with a risk of heart disease. 

Approximately one~ fourth of Americans luve elevated trig!yr-erides. See MMgarct D. Carroll. Brian 

K Kit. and David A. Lacher, ''Trends in Elevated Triglyceride in Adults: t!nitcd States, 2001 2012" 

(NCHS D::~.t:t Krief 1'\o. 1q8, Center,;; for Disease Conrrul, M~1y 2015!. 

33 
146 

approval. Medical experts made the case to the FDA that the drug should be 

approved at this time for lowering triglyceridcs (even if not for reducing risk of 

cardiovascular outcomes in patients with triglyceride levels ahove 200 mg/dL) 

for a very practical reason: patients with triglyceride levels a hove 200 mg/dL 

are often taking fish oil supplements on their own. However, the supplements 

are not of defmite composition and quality, and they often have impurities 

that arc deleterious to patients' health. This common-sense argument did not 

sway the FDA. 

But on 1\Uf,"\ISt 7, 2015, in their ruling on /\marin's lawsuit against the FDA, 

the federal courts stated that the company"may engage in truthful and nonmisleading speech promoting the off-label usc of Vase epa." Now, Amarin is 

permitted to market Vase epa for usc in patients with triglyceride levels above 

200 mg/dL under its First Amendment rights to free specch.61 The FDA has not 

amended its policies in light of the Amarin decision. 

Low HDL Cl;ol<,"•l•,•t(ll 

Low HDL cholesterol is a known risk factor !(Jr patients with cardiovascular 

disease, butt he FDA has not approved drugs that raise IIDL cholesterol despite 

the fact that several agents have been shown to be effective at doing so. Niacin, 

for example, increases HDL; however, it was not shown to decrease MACE 

outcomes. Many doctors believe this was due to confounding issues in the trial, 

and-""since niacin is available-such doctors use niacin to increase IIDL. 

Drugs of a new class called CETP (cholesteryl ester transfer protein) 

inhibitors hm"e shown significant effectiveness in raising HDL. On October 12, 

2015, Eli Lilly announced that the development of its CETP inhibitor, evacetrapib, was stopped even though there were no safety issues because the trial 

was unlikely to show a reduction in cardiovascular events, as determined hy the 

independent data-monitoring committee. This is unfortunate because there is 

no telling how this drug may have been shown to he beneficial when used in 

the real world. The FDA's insistence on cardiovascular outcomes data obscures 

the medical imperath·e of raising l!DL and the potential hcncftts that could he 

assessed in actual use and in post-approval studies in subpopulations of patients 

with low HDL levels.'"' Nevertheless, ifHDL cholesterol can be increased safely 

61. Thom1s M. Burton, ''Amarin \\'ins Off-Label Case 3gainst FDA," Wail Street Journal, August 7, 

2015, http:f/wv.·v,r. wsj.com;articles/amar in-\.Vins-off-lahe l-ease- against-feb_-! 43 89617 4 7. 

62. The studies ofCETP inhibitor:,; <tre tbwed in the sense that the CETP inhibitors are administered 

on top of optimum sutin therapy; it is likely that the effect dr:.tising lD)L is p~utlymaskeJ in the 

:>tudics by the benefits coniCtTed hy lowering LDL. 

34 
147 

and reliably, why shouldn't agents be approved so that doctors in the medical 

marketplace can determine clinical utility in their patients, especially upon 

review of subgroup mwlyses and trend identification from pre-approval studies 

and large post-approval studies? 

Pr ostnte Cnncur 

The circumstances surrounding the use of Taxotere (docetaxel) in prostate 

cancer also shed light on the medical marketplace in action and on what doctors need to see before early adopters usc new drugs. This particular drug was 

originally approved in 1996 for breast cancer." A Phase !/II trial in prostate 

cancer in 34 patients, published in 1999, demonstrated a 50 percent decline in 

PSA (prostate specific antigen) and five partial responses (significant reduction 

in the size of tumor lesions); 8 of IS patients were able to discontinue narcotic 

analgesics Ltse for bone pain."" 

Unfonunately, it was not until two phase III studies ofTaxotere versus 

mitoxantrone in hormone refractory patients were conducted that Taxotere 

was approved for use treating prostate cancer patients on May 19, 2001. A 

statistically significant suryival advantage (18.9 months versus 16.5 months) 

was demonstrated." 

The six-year delay in Taxotere's approval for use on prostate cancer so 

that improved snrvival could be demonstrated made no sense, given that the 

drug was approved t(,r use on breast cancer in 1996 and there was strong evidence of its activity on prostate cancer in 1998.66 Luckily, Taxotere was given 

a compendium listing by Medicare, so there was a tremendous amount of offlabeluse of the drug occurring in the medical marketplace before the accumulation of sun•ival outcomes data: 

A study on the diffusion of use ofTaxotere in medical practice 

demonstrated that hroaderuseofDocctaxel [Taxntere] preceded 

63. l'J.xoterc (1Joc:etaxel\ CenterWatch, accessed Jamt3ry 21, 20l6, https://V.'\VW.ccntcnvatch.corn 

64. DanielL 

Prostate Cancer," Jounw/ ufC/ini<'<Ii Oncdogy 17, no. 3 (I\1;u·ch 19-JQ): 958 (,7, 

65. "FDA Approval fur Docelaxd," N!H ~aliunal Cancer In..-titute, last modified March 28.2014, 

http:/ jwl..VW .cancer.go v /about -cmcer /tTeat:ment/drugsjfda-docct:J.xe L 

66. The .American Cancer Society estimates that there will be over 200,000 new nses of prostate can~ 

cer in the Lnited ~tates in 2015 :1lone. See ''I [oR· :Vhny Men Get Prostate Cancer{," American Can<:er 

Society, January 30, 2015, http:/ j;.vww .cancer.org/c .mcerjprosi atecancer /overviewguide/prostate 

-cancer-overview-kcy-st:Itistics. 

35 
148 

phase III evidence for its eflicacy, indicating extensive off-label 

use.67 

The off-label use ofTaxotcre in the med icalmarketplace was a very good thing, 

but how many more patients could have benefitted had the FDA approved Taxotere i(lr use when ample evidence of its potential had been accumulated years 

in advance? 

Female Hc'c1ltl1 

The FDA's extreme caution is evident even after drugs arc approved and have 

been on the market for years. Take, for example, combination hormonal contraceptives (bird1 control pills, rings, and patches). These products are so safe that 

California and Oregon haw announced that they will be made available over 

the counter despite their current FDA prescription drug labeling. That labeling 

contains very frightening language (called "class labeling") conveying safety 

concerns, particularly for women who smoke and who are over 35 years of age. 

However, the condition that contraceptives prevent-that is, pregnancy ·-also 

poses risks, often much greater ones. The FDA's labeling does not include fair 

balance because it fails to report on the risk of similar adverse outcomes from 

pre~nancy. In short, the FDA doesn't conduct proper risk-risk analysis. 

67. Joseph i\'I. Unger et al., ·The Diffusion ofDocctaxel in Patients with Metastatic Prostate CanC'er," 

Jow-rh1f of th<I J\fationa! Cancer 1 mtiwte 107 (201 S} dju412. 

36 
149 

Joseph v. Gulfo, MD, MBA, is the author of The Care Quotient: Transforming llusiness through People and innovation Breakdown: How the FDA and 

Wall Street Cripple Medica/Advances. He is executive director of the Rothman 

Institute of Innovation and Entrepreneurship at Fairleigh Dickinson University, where he is spearheading the Tnitiative for Patient-Centered Innovation. 

He is also a visiting scholar at the Mercatus Center at George Mason University. A contributor to The Hill and Inc., he also teaches graduate-level cancer 

biology, business and entrepreneurship, and MBA classes and maintains an 

educational cancer biology blog. Gulfo received his MD from University of 

Medicine and Dentistry of New Jersey and his MBA from Seton Hall University. He was responsible for the approval of a monoclonal antibody for prostate cancer (ProstaScint), a drug for bladder cancer (Valstar), and a medical 

device for melanoma detection (MelaFind). Gulfo is also on the faculty of the 

GLG lnstilllte MastcrClass program and a member of the Life Science Council of Springboard Enterprises. 

Jason Briggeman is the managing editor ofEconJouma/ Watch, and he teaches 

economics at Central Texas College. He received his PhD in economics from 

George Mason University, where he wrote his dissertation on pharmaceutical 

regulation. 

Ethan C. Roberts is an MA fellow with the MercalUs Center at George Mason 

University and a graduate student in George Mason University's department 

of economics. 
150 

ABOUl l!!l. !vH"U\i N1 

The Mcrcatus Center at George Mason University is the world's premier 

university source for market-oriented ideas-- bridging the gap between academic ideas and real-world problems. 

A university-based research center, Mcrcatus advances knowledge about 

how markets work to improve people's livesbytraininggraduate students, conducting research, and applying economics to offer solutions to society's most 

pressing problems. 

Our mission is to generate knowledge and understanding of the institutions that affect the freedom to prosper and to lind sustainable solutions that 

overcome the barriers preventing individuals from living free, prosperous, and 

peaceful lives. 

Founded in 1980, the Mercatus Center is located on George Mason University's Arlington and Fairfax campuses. 
151 

2.11912016 FDA must focus on drug safety and effect1vermss oot pa\1ents' life outcomes I TheH!H 

February 19,2016, O?·oo am 

FDA must focus on drug safety and effectiveness, 

not patients' life outcomes ByJosephGulfo,contributor 

As the Senate Committee on Homeland Security and Governmental Affairs meets next week for a hearing on "Connecting Patients to New 

and Potential Life Saving Treatments," it is Important to remember the appropriate role of the Food and Drug Administration (FDA) in 

promot1ng the health of Americans. (Full disclosure I have been called as a witness to testify at th1s hearing.) 

The FDA's mission IS to provide doctors tn the medical ecosystem with access to safe and effectiVe new drugs, biologics, and devices in a 

prompt, efficient and timely manner. The medical marketplace, whtch involves patients, payers and physicians, functions to then 1dent1fy, and 

preferentially use, the most appropriate products in 1nd1vidual pat1ents. This is how the law was destgned. 

Despite incessant pleas from doctors and patients for more safe and effective products that m1ght help when used appropriately. the FDA 

contmues to raise the evidentmry threshold for permitting a new product- recasting pre-market approval as a venue for the practice of 

evidence-based medicine to determine dinica! utility. benefit, and health outcomes, pre-approval. This move 1s aimed at satisfying FDA critics, 

but it consumes precious time and resources. and it dissuades drug developers (and would-be developers) from pursuing projects 

The FDA has acknowledged the changes 1111!s standards for product approval. In a March 10,2015, opinion piece. two high-ranking FDA 

offic1a!s had !h!s to say about the review process '"It is important to remember, however. that innovative therapies only save hves 1f they work 

properly. U.s. citizens rely on the FDA to ensure that the drugs they take are effective and that their benefits outweigh the1r risks. lmprovtng a 

patient's life or lifespan must be central to the concept of drug tnnovat1on." 

But the FDA is supposed to assure safety and effect;veness of drugs, not life outcomes for pat1ents. A drug's proposed label indicates the 

effect 1! is purported to have: safety and effectiveness are to be determmed 1n the context of that labeling. The phys1c1an and the patient. acting 

in the med1cal marketplace, are to determine whether and when taking the drug w1ll be conducive to 1mprovmg a patient's life. That we 

authonze physicians to prescnbe drugs off-label is 1nd1cat1Ve of this division of labor 

Certainly. studtes of life outcomes can be invaluable to informed decision-making by physicians and payers. But there are many and varied 

factors that contribute to disease development, progression and response to therapy. It IS far harder to produce good knowledge about life 

outcomes for patients than it 1s to produce good knowledge about a drug's safety and effectiveness with respect to spec1fic disease-related 

parameters. 

Moreover, the appropriate place to evaluate life outcomes 1s in the post-approval setting, by the medical marketplace. Trying to do so preapproval. before a new drug has settled into practice. is not scientifically prudent. The myriad of real-world factors that may modulate ultimate 

clinical benefit cannot be known or control!ed m pre-approval studies, no matter the s1ze. Without mformed data that become available only 

after a safe and effective drug has been 1n use for a penod oft1me. Thus, the way that FDA currently approaches drug approval can actually 

mask chnica! b8nefit. If chnical utility is used as the cntena for approval. many drugs that are safe and effective and could help pat:ents w11! 

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2/19/2016 FDA must focus on drug safety and effectiveness. not pat1ents' life outcomes 1 TheH!l! 

never see the light of day. 

The other problem w1th the FDA's current approach is that 11 is directly contrary to the precision medicine movement The FDA makes 1ts 

determinations based on the responses ofthe average pat1ent in clinical trials. While immediate- and near-term measures of effectiveness 

(reducing pa1n and tumor size, and increasing air movement 1n the lungs, for example} are appropriately evaluated by calculating average 

pat1ent responses, clinical benefit is not appropriately assessed in this manner. Many patients may truly benefit from a drug, however, the 

benefit may not be seen in enough pattents to pass the average patient hurdle. As long as the drug 1s safe and effective as per Its labeled 

conditions of use, clinical benefit should be the domain ofpat1ents and doctors. not the FDA 

In essence. the FDA, which should be the gatekeeper of safe and effective products that enter the medical armamentanum. has put Itself in 

the position of JUdging which drugs are most beneficia!. The funnel d1agram available here. in a piece I co-authored for the Mercatus Center, 

depicts the roles and responsibilities of medical marketplace consl1tuents in the diffusion of new drugs and devices into practice. The law 

provides for the FDA to be at the top of the funnel and for the medical marketplace to dectde from among the FDA-approved safe and effective 

products which are the most beneficia!· therefore, which are used the most (bottom of the funnel). However, the FDA, in demanding data from 

drug developers. pre-approval, to determine whtch drugs are most beneficta!, is puttmg t!se!f at the bottom of the funnel as well. 

At no other time in history have we been better equtpped to pertorm real-world, large-scale outcomes and survival studies with regard to 

medtca! Interventions, such as the use of safe and effective drugs and devtces. There IS no way that pre-approval studies of drugs and 

devtces in tightly defined patten! populattons under scripted medical management protocols, can produce the kind of evidence that is available 

through real-world data acquisition and the Internet of Things. What's more. in the post-approval. real-world settmg, data that wtll enhance the 

selectton of therapy for an indivtdual patient can be made available in an unprecedented manner, which can truly drive personalized medtctne. 

The law instructs the FDA to constder new drugs for approval on the bas1s of the uses submitted by sponsors. Sponsors are responding to 

needs identified in the medical marketplace. The FDA should not be telling sponsors that thetr drugs must show Improvement in cllmcal 

outcomes; rather, the FDA's role is to label drugs as ··safe" for uses that the agency finds substant:al evidence has been presented. It is then 

the job of doctors in the medtcal marketplace to determine the beneftts and risks of using new drugs tn individual patients, mformed by the drug 

label, their expenence with the drug. post-approval studies, and individual patient factors 

As discussed in my recent paper noted above. "The Proper Role of the FDA in the 21st Century." it is imperative that the FDA get back to 

focusmg on safety and effecttveness as the pre.approval standards. The now of new innovatNe therapies that can advance health is 

dependent upon all players In the medical marketplace performing the1r roles. starting with the FDA making safe and effective products 

ava1!ab!e. We the public and Congress need to acknowledge that the FDA has a dauntmg enough responsibility to ensure that new medical 

products are safe and effective. and avoid the p1tfall of also demanding pertect public and pnvate health outcomes from the FDA, which is 

simply :mpossible. It IS fear on the part of the FDA that has dnven 1t to demand proof of c!tmcal utility and benefit 1n lieu of safety and 

effectiveness. The first step is acknowledging that medicine is an art. not a science, and that the FDA is not the lone participant 1n the medical 

ecosystem that IS responsible for advancing the health of Americans 

Gu/fo IS the executive dtrector of the Rothman Ins Mute of Innovation and Entrepreneurship <Jt Fairleigh Dickinson University and author of 

"Innovation Breakdown: How the FDA and Wall Street Cripple Medical Advances" (Post Hill Press) He has more than 25 years of 

experience m the bJOpharmaceut!ca/ and medical-device mdustries and 1s the former CEO of Me/a Sciences. Fo/fow him on Tw1tter 

@josephgulfo 

TAGS: Food and Drug Administration, FDA, Drug, pharmaceutical, approval 

The Hill11l25 K Slreet, NWSui!e 900 Washmglon DC 20001) 1202-028"8500 !ell202-628-85031ax 

The conten!s ofth!s srle are ©20Hl Capdol Htl! Publishmg Corp. a subsid•ary o! News Comrflun•cat•ons, !nc 

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2/1812016 Meel FDA cnt1c Joseph Gulfo, the Antonin Scalia of lhe l!fe sc1ences- Boston Busmess Journal 

I. l 

FOR THE EXCLUSIVE USE OF JOSEPHGULFO@GMAIL.COM 

From the Boston Business Journal: 

http://www. bizjou rna ls.com/bosto n/bl og/bioflash/2016/ 02/ mecct · 

fd a-critic·joseph-g u lfo-t he-ii 11ton in ·sea I ia-of. html 

Meet FDA critic Joseph Gulfo, the Antonin 

Scalia of the life sciences 

Feb 17, 2016, 2:28pm EST 

If scientists still can't determine 

whether coffee, red wine and aspirin 

are ultimately good for us, how can the 

U.S. Food and Drug Administration say 

whether any of the drugs it reviews will 

help patients in the long run? 

That's one argument made by Joseph 

Gulfo, the main author of a paper 

questioning the federal agency in 

Joseph Gulfo, MD, is author of the book, "lnnovation 

Breakdown," and an outspoken cnnc of the FDA. 

charge of approving new drugs. His point of contention: There's been 

a kind of mission creep at the FDA over the past two decades beyond 

its original role of making sure drugs are safe and effective. 

Gulfo, the former CEO of MELA Sciences, argues the FDA too often 

interprets the meaning of "effective" as beneficial for the average 

patient over the long run, as opposed to simply doing what the 

drugmaker claims. He argues that evidence of long-term benefit only 

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zr18!Z01G Meet FDA cnt1c Joseph Gulfo, the Anton1n Scalia of the life sciences- Boston Bus1ness Journal 

comes after widespread use, not from clinical trials. It's a distinction, 

he says, that keeps too many potentially beneficial drugs off the 

market. 

There's a long list of drugs that have been rejected- despite patient 

objections- because the FDA said they didn't prove effectiveness. 

For example, Lemtrada, the multiple sclerosis drug by Sanofi 

Genzyme (NYSE: SNY), was denied approval in late 2013, only to be 

approved about 10 months later with no new trial information. And a 

kidney cancer drug by Aveo Oncology (Nasdaq: AVEO) was rejected 

in 2013 despite showing more efficacy than existing drugs in slowing 

the disease's growth. And Sarepta Therapeutics (Nasdaq: SRPT) is 

now facing a harsh review from the agency over its potential drug for 

Duchenne muscular dystrophy despite hundreds of patients willing to 

take the risk that the drug may not work as well as it has in a 12-

patient trial. 

Gulfo co-authored his FDA critique with Jason Briggeman and Ethan 

Roberts. All three are affiliated with the Mercatus Center at George 

Mason University. 

In an interview last week, I asked Gulfo whether the FDA should lower 

its standards for proven effectiveness. His response: 'Til never say I 

want lower standards. I want effective drugs." 

"A lot of times I tell people, 'Don't blow up the FDA. We need them to 

do what they do,"' he continued. "But they have to do what they were 

put into business to do- not more .... they've now ordained 

themselves as the arbiters of clinical utility. And that's not in the law." 

Gulfo also said the FDA's study mandates often "mask benefit," 

saying, "I really believe benefit can only be determined when (a drug) 

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2!1812016 Meet FDA cnt1c Joseph Gullo. the Antonm Scalia ot the !ffe sc1ences- l:loston \.iusmess Journal 

is on the market." 

Another problem with the current system, Gulfo says, is a focus on 

the "average" patient. Plenty of people get a benefit from drugs that 

don't prove they help the average patient, he said. Gulfo argues that 

the FDA is usurping the job of patients and doctors in saying what 

drugs a patient should try. 

You could describe Gulfo as an "originalist" of the law that created 

the FDA in the same way Justice Anton in Scalia was an originalist in 

interpreting the Constitution. The fact that the FDA requires 

increasingly large trials for drugs for diseases that affect millions of 

patients- like diabetes, Alzheimer's or obesity- means fewer 

companies want to attempt to develop those drugs. Instead, drugs for 

smaller and smaller subsections of cancer patients (oncology drugs 

make up more than a third of all drugs being developed in the Boston 

area) are becoming more and more popular. 

"The beauty of today's medical marketplace is, now you have the 

payers saying, why do we pay more for this drug? Because they've 

proved survival versus just raising the HDL," he said. "So now the 

companies, post-approval, would be competing that way. But (the 

FDA) wouldn't be the gatekeeper to getting it on the market based on 

safety and effectiveness." 

Don Seiffert 

BioFiash Editor 

Boston Business Journal 

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COMMENTARY: Return FDA to its proper role 

.IOSf:l'li V. Gt:LFO L' 1//j am J:';f l·chr~run . :;'iiff• 

VVhen! received my driver's license my father said to me, "Congratulations, son- now you really !earn how 

to drive." Driver education courses only ensured that! knew how to operate the veh1de safely and 

appropnately to get from po1nt A to point B. I had eight fender-benders in my first decade behind the wheel. 

and I haven·! had one accident for the last decade. My father was right I learned how to operate a car very 

well- after I had my license for a wh1le 

If the Department of Motor Vehicles approved driver's licenses like the Food and Drug Administration 

(Photo· Gel/y lrnagesi1Stockphoto) approved new drugs and devtces, driving tests would go on for months and cost a tremendous amount of 

money. I would have been tested on driv1ng to points 8 to Z and countless other scenanos. It the DMV 

started doing this, Americans would surely say the DMV had lost 1ts way 

Well, the FDA has lost its way and as President Barack Obama's nominee for commissioner of the FDA- Or. Robert Califf- moves through the 

nom1natton process, the agency's proper role in the medical ecosystem should be scrutinized. 

Congress tntended the FDA to lic-ense drugs for approval, and then let the medical ecosystem prescribe the drugs in real world circumstancesguided by FDA's licensing instructmns, of course- to arrive at the most appropnate uses for individual patients. 

The FDA's role is dearly defined in the Federal Food Drug and CosmettcAct "to promote health by promptly and efficiently reviewing clinical research 

and taking appropnate action on the marketing of regulated products tn a ttmely fashton." Th1s includes "'ensunng that ... drugs are saf-e and effecttve 

(and) there is reasonable assurance of the safety and effectiveness of devtces " 

The two most important parts of the FDA's mission are to judge new products on the basis of safety and effectiveness, and to do so quickly. The 

med1an lime of approval of novel drugs is 304 days. Considenng that 10 months is the target revtew penod for a!! new drug applicahons, the FDA ts 

late half the t1me. 

The reason that the FDA is incorrigibly late, and the reason that many companies don't even try to develop drugs for many diseases that affect 

md!ions of Americans, ts because the FDA has lost stght of its proper role. The FDA ts supposed to be the gatekeeper of medictnes that become 

available to the medtca! marketplace of physictans, patients. hospttals, payers, and medtca! communtty. Congress mtended for the FDA to approve 

only those drugs that could be labeled for safe use and demonstrated the clinical effects c!atmed by drug developers. 

Instead. the FDA is tmposing its own standard for what constitutes a good drug. Rather than licensing products for use by doctors, the FDA is trying to 

dictate the practtce of medictne. Rather than entenng products that are safe and effective into !he medical marketplace for the physictans to use and 

determine which are best for indtvtdual patients. the FDA ts endeavormg to tell doctors and patients. upon approvaL whtch drugs are best and how 

they are to be used. This is not how the system was set~up. nor 1s it posstble 

In my recent research paper for the Mercatus Center on "On the Proper Role of the FDA.' we make the case for the FDA to return to 1ts proper role 

arbiters of safety and effectiveness, period. The FDA must be stopped from insisting on !ong~term outcomes that requtre humongous clinical trials 

which are exceedingly difficult, time consuming, and costly to demonstrate. especially before approvaL lf the FDA were returned to its proper role, new 

drugs would be approved quickly, true personalized med1c1ne would be facilitated, and bolh drug development costs and prices would be reduced 

You and your doctor need to dec1de which therap1es are best for you and Wh!ch are most benefictal. not the FDA. The only way that can happen is 1f 

the agency assumes its proper role in the medical ecosystem 

Joseph V Gu/fo is a VISiting scholar with the Mercatus Center at George Mason University and executive director of the Rothman Institute of 

Innovation and Entrepreneurship at Fairleigh D1ckmson UniVersity: He wrote this for Inside Sources com 

Read or Share this story http.//on.cpsj.comf1T5ZWfG 
157 

1212212015 Appropriate oversight !S needed to change FDA behaviors, not more laws I TheHill 

December 22, 2015, 07:00am 

Appropriate oversight is needed to change FDA 

behaviors, not more laws ByJosephGulfo,cor!tributor 

Joseph Gullo 

Oversight of the executive branch is a main duty of Congress that flows from the many and varied express powers of Congress in the 

Constitution, including appropnat1ng funds, enacting laws. and impeaching and removing civ1! officers. However, as former House Speaker Tip 

O'Neill (0-Mass.) once exclaimed, "Members like to create and legislate, but we have shied from both word and deed of oversight." 

Not only has Congress shied away from overs1ght, it has been used more as a "fire alarm" than as "pobce patrol," in the words of Mathew 

McCubbins and Thomas Schwartz. Congress has been deficient In "police patrol" oversight- that is, constant watchful VIgilance to ensure 

that Food and Drug Administration (FDA) laws are enacted dutifully. But it has been qwte aggressive in exercising ''fire alarm" overs1ght that 

comes from hearings in response to events, for example, adverse react1ons with medical products 

There have been many high-profile hearings on drugs including antidepressants Vioxx, Rezu11n and Avandia. In aU of these, the FDA is 

basically accused of inappropriately approving products that are unsafe. Of course, the 1ssues are not so cut and dry. This kind of knee-jerk 

oversight. which provide great theater and incentives of their own, greatly damages the cause of medical innovation· As former FDA 

Commissioner Alexander Schm1dt sa1d in 1974· "In all of FDA's history,! am unable to f1nd a single rnstance where a cnngress1onal committee 

1nvest1gated the failure of FDA to approve a new drug. But the t1mes when heanngs have been held to cfl!iCize our approval of new drugs have 

been so frequent that we aren't able to count them The message to FDA staff could not be clearer." 

The case of Avand1a 1s particularly d1sconcertmg. Even when the FDA does the nght thmg- for example, approving an excellent drug that 

helps millions of patients- 1! 1s castigated and publicly humiliated. A New England Journal of Medicme publication of a meta-analySIS of 42 

small chmcal trials revealed an increased fikel!hood of sig!lificant cardiovascular toxicity in patients tak1ng the drug, so the FDA restricted the 

drug's use in response to pointed criticism at a congressional hearing. Here is what the FDA had to endure at a Se!late hearing on the matter 

''This report poses several troubling questions for thiS subcommittee. Most obviously. if Avand1a is unsafe, how did it ever get on the market in 

the first place? For that matter, why is it stl!! on the market, right now? And what does the case of Avandia tel! us about the FDA's current 

ab1Hty to conduct its drug safety responsibilities?" 

Subsequently, the FDA removed the restnct1ons from the label when the drug was shown not to cause i!lcreased cardiovascular problems, 

following a re-analysis of a very large prospective study, rendering the meta-analysis flawed. But the damage was done: The FDA changed 

the regulations to require larger and larger clinical trials and disease outcome endpomts for products that are mtended for large chrome 

diseases, like diabetes. Knee-jerk oversight triggered by a flawed analysis had severe un1ntended consequence. 

Sadly, Or. Robert Califf, nominated to be the new FDA commissioner, was in full support of erroneously demanding larger and larger trials in 

the midst of the Avandia saga. As Matt Herper wntes, "In 2008, after Steven Nissen from the Cleveland Clime had openly cntiCIZed Avandia, 

the GlaxoSmithK!ine diabetes drug, he proposed a new standard for studying dmbetes medicines that would ins 1st they be tested 1n din1cal 

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12122/2015 A.ppropnate overs1ght ts needed to change FDA behavwrs. not more laws! TheHH! 

trials involving thousands of patients to see tf they had any effect nn heart attack rates_ When Nissen mentioned the tdea at an open public 

meeting, Califf was fast to back it." And, these saris of unnecessarily large, expensive and time-consuming studtes have remained as the new 

standard, they were not walked back when the case of Avandta was shown to be a false alarm. Just last week, the FDA noted the following 

"continued monitoring" of Avandia. Avandamet and Avandaryl had turned up "no new perttnent safety informatton'" about the drug. So. the 

agency lifted the final layer of safety measures that It erroneously imposed. But sales of the drug were crushed; as reported by FiercePharma. 

'The safety questions drove Avandia revenues down from a peak of $3 billion before the controversy to $183 million in 2011, just before 

generics hit the market." 

At the Senate HELP (Hea~h, Education, Labor and Pensions) committee's cortfirmation hearing for Califf on Nov. 15.2015. he doubled down 

Sen. Elizabeth Warren (D-Mass.): Do you agree with arguments to lower standards for FDA approval of drugs and dev1ces? 

Califf: ! have never been a proponent of lowering standards for anything. ___ ! have been 1n favor of ra1s1ng standards. In no case would I 

argue to !ower the standard. I think I have been staunch in that regard 

!tis understandable that the FDA would retrench when 1t 1s attacked. The agency then protects itself from future attack by: (1) raising the bar 

for product approvals by moving away from the statutory criteria of safety and effectiveness and demanding proof of chnica! ut1lity, clinical 

outcomes and survival: (2) demanding larger and larger tnals that cost tremendous ammints of lime and money, (3) shifting 1ts emphasis to 

pre-approval reqUirements versus a balance of pre-approval data and post-market controls and surveillance: and {4) preferentially approving 

products for mche diseases rather than those that affect ml!ions of Americans 

After the FDA retrenches in response to criticism and then issues new rules and guidance documents with alternative interpretations and 

implementations of the laws, Congress does not perfnrm the appropriate police patrol oversight to re-direct the FDA back to 1ts mandate, 

forcing the FDA to honor the letter and spin! of the laws that are passed. No, it does something worse: !tactually passes more laws. for 

example, as part of each PDUFA (Prescnpt1on Drug User Fee Act} and MDUFA (Medtca! Device User Fee Act) reauthonzation that takes 

place every five years. and 1n other legislation, like 21st Century Cures. This legislation. drafted in consultation With the FDA, then codtfies the 

FDA's new pos1tions taken tn response to inappropnate fire alarm oversight 

The vtcious cycle starts over again the next lime an unfortunate adverse events occur with drugs and devices that are on the market. which 

will invariably come to be. And this is how regulation kills medica! innovat;on and hurts pa!Jents. 

In our latest Ml3 Alert, we examine the effects of this vicious cycle and offer solu!!Ons to reducing regulatory burden so that medical 

innovations that can truly promote the health of tens of millions of Amencans can flourish. keeping pace W1th the amazing scientific advances 

that are being made. Unfortunately, better oversight. alone, cannot accomplish this- we need some laws to undo the damage that many 

turns of the vicious cycle has wreaked. For example, the FDA must be made to return to safety and effectiveness {as measured by activity in 

modu!atmg disease signs and symptoms, surrogate endpoints and biomarkers) and allow doctors and patients to determ1ne clif'!cal benefit. Of 

course, better overs1ght will require yearly reports of FDA performance with respect to product reviews and approvals in comprehensible 

terms. like calendar days and averages. as we!l as reports from the FDA ombudsman regardmg tssues that arise between the FDA and drug 

developers. And Congress should resist the temptatton to publicly flog the FDA at fire-alarm hearings when unwanted unfortunate toxicrt1es 

anse, which they invanably will, this JS the nature of medical and scient1f1c progress 

As Speaker Newt Gingrich said. 'This is the city [Washington] which spends almost all of its energy trying to make the nght dectsions and 

almost none of its energy focusing on how to improve implementing the right dectsions. And without 1mp!ementahon. the best ideas 1n the world 

s1mpty don't occur." 

We have excellent ideas that are not reaching patients. We need congress to start periorming oversight appropnately to make the FDA's first 

priority 1s promoting health. not protecttng itself from attack 

Gulfo is the executive director of the Rothman lnstituto of fnnovatwn and Entrepreneurship at Fairleigh Oickmson Umversity and author of 

'1nnovation Breakdown: How the FDA and Waf/ Street Cripple Medical Advances" (Post Ht/1 Press). He has more than 25 years of 

experience in the biophBrmaceutical and medica/-dev1ce mdustnes and 1s the former CEO of Meta Sciences. Follow him on Twitter 

@josephgulfo 

TAGS: Vioxx, Re.zulin, Avandia, Food and Drug Administration, FDA, Robert Califf, DI1Jg, pharmaceuticals 

The H11! 1625 K Street. NW Su11e 900 W11shmgton DC 20006! 202-628-8500 WI) 202-528-8503 filx 

fhe ('.Qntents of\hts stle are ©2015 Capttol Htll Publtsh•ng Corp a SlihSidtary of News Commurw:altons Inc 

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159 

Ml 3 Alert -

Initiative for 1 Patient-Centered 

l! !J Innovation 

Medical Innovation lmp,Jct lnciex 11/:50/15- Report ttl 

General Oescnptton of Issue 

Oversight of the Executive Branch IS a mam du:y of Congress that is a:l Implied, rather than an e1;umeratcd power- 1t was seen 1n 

the Federalist Papers (48, 49, and 51) ilS <1n <nherent power of representative assemblies, which enactea public law. Oversight also 

derives from the many, varied express powers of the Congress in the Constitution is implied 1n the legislature's authonty, among 

other powers and duties, to appropriate tunas. enact laws, and impeach and remove from office the President, Vice President, 

and other civil officers. Congress could not reasonably or resporsibly exerc1se these poWers without knowmg what the executive 

was doing: how programs were being admlmstered, by whom, and at what cost: and whether officials were obeying the law and 

complying with legislative intent. However. as former House Speaker Tip O'Ne1ll once exclaimed, "Members like to create and 

legislate, but we have shied from both word and deed of oversight." As former Speaker Newt Gingnch sa1d, "This IS the city 

[Washington, DC] which spends almost all of its energy trymg to make the rrght dec1sions and almost none of its energy focusing 

on how to 1mprove implementing the right dec1s1ons. And Without implementation, the best ideas 1n the world simply don't occur." 

Congress certainly expends great effort passing laws that hove the goal of enhanc1ng medic<:~! innovation, for example PDUFA 

(Prescnpt1on Drug User Fee Act) <;~nd MDUFA (Medical Dev1ce User Fee Act) reauthonzabon. The quest1on •s whether better 

Congressional oversight would result in a greater number of more profound medica! 1nnovat1ons reach1ng patients more quickly. 

Purports To Do 

Congressional oversight of the FDA could be a very powerful 

force to ensure that the letters and spirits of FDA laws are 

enacted in a manner that truly enhances medica! 1nnovation. 

Congress has at its disposal many opportunities to conduct 

this oversight, mduding: (contmued on pg. 2) 

Success in Achieving Objective: +3 

Potential Postttve Impact on Innovation 

The potent1al pos1t1ve 1rnpact on medical mnovat1on th<'lt 

would follow effectiVe CongreSSIOnal oversight IS enormous. 

Oversight on JUSt a handful of policies could have a huge 

impact (contmued on pg. 2) 

Positive Impact on Innovation: +3 

-1 

Unintended Consequences 

Inaccurate Performance Reports: 

As mentioned above, the FDA IS required to make reports to 

Congress on review time performance under PDUFA [FedNaJ 

Food. Drug, & Cosmet1c Act (FD&C) (continued on pg. 3) ... 

Emergence of Unintended Consequences: -3 

Potential Negattve Impact on Innovation 

Congress has been deficient m "police patrol" oversight, that 

IS. constant watchful vigilance to ensure that FDA taws 

are enacted dut1fu!ly. But, 1t has been qu1te aggress1ve 1n 

exercising "fire alarm" overs1ght that comes from hearings 1n 

response to events, for example adverse (continued on pg. 6) ... 

Negative Impact on Innovation: -4 

1111111111111111~~ ~,;~:1111111111111111 -10 10 

If poor oversight were eliminated and proper oversight were implemented, a substantial positive impact on 

medical innovation is likely 

Recommendations 

As Walter Oles.<:ek of the Co:lgress1onal Research Se<vice states ~r< Congress1onat Overstght. An Overv1ew. 

Congress;onal oversight ideally involves the continuous review by the House and Senate, especially through the1r committee 

structures. of how effectively and efficiently the executtve branch is carryrng out legis lot we mandates. The "continuous 

watchfulness" precept-an ob!igatJon statutonfy ass1gned to the standing commtttees by the Legisfative Reorgonization Jkt of 

7946-implied that Congress would henceforth parttcrpate actively in adminiStrative decisiOn~ making, in fine (contmued on pg_ 10) ... 
160 

Ml 3 Alert Med1cal Innovation lrrlp<:Kt lnck;x 11/30/15- Report #7 ~ Page 2 

Purports To Do (contmued from pg. 1) 

1. Hearings and investigations~ her-.rings, m particular, focus generally on the efficten.cy and effectiveness of federal agencies a no 

programs. They are also conducted in response to issues that anse as a perceived consequence of agency action or inaction_ 

2. Authorizing process~ the regular reauthorization process of laws focuses great attention to spending and whether the spending 

authorized by Congress results in the destred effects. For example, POUFA and MDUFA require reauthorization every 5 years. 

3. Appropriations- as James Madison stated, "The power over the purse may, in fact, be regarded as the most complete and 

effectual weapon with which any constitution can arm the Immediate representatives of the people, for obtaming a redress of 

every grievance, and for carrymg into effect every just and salutary measure." 

4. Inspectors General- conduct 1nvest1gations and audits of agencies to improve efficiency, end waste and frdUd, discourage 

mismanagement. and strengthen the effectiveness and economy of agency operat1ons. 

5. Government Accountability Office- the office subm1ts reports to Congress annually. describing ways to root out waste and 

m1smanagemen: in executive branch programs and to pro•note program performance. 

G. Reporting Requirements- numerous laws reqUJre executive agencies to subm1t reports periodically, and as reqUired by soeC!flc 

events or certain cond1t1ons. For exr1mple, lhe FDA 1s requ1red to prov1de Congress w1th yearly reports of rev1ew performance 

under PDUFA and MDUFA 

7. Senate Confirmation Process- through publiC quest1on1ng and rev1ew of credentials of md1viduals nominated by the President 

to lead agencies, Congress can bring to light tssues 1n the implementation of the law by the agencies. 

8, Casework* activities by members pursuant to Issues raised by lndivld<.Jal constituents. 

9. Informal- member and staff contacts w1th agency personnel. 

To the extent that many portions of FDA laws are des1gned to promote health through med1cal innovation, Congress has the 

mandate and multiple means at its disposal to conduct appropriate and effective oversight to ensure that the provis1ons and 

programs are be1ng enacted as mtended and uch1eving the deswed goals. 

Potential Positive Impact on lnnovat1on (continued from pg. 1) 

l. If PDUFA and MDUFA review time goals were enforced. drug approval times would be cut 1n half and new devices would reach 

patients much more quickly: 

a. !n 2013, the FDA's median approval t1mo for drugs wus 30<1 days- this means that rev1ew times exceeds the PDUFA goal of 

10 months for SO% of applications. 

b. In the f1rst half of 2015, the av('rage rev1ew time for a Pre-Market Approval Application (PMA) was 17,1 months (MDUFA goal 

180 days) and Humanitanan Dev1ce Exemption (HOE) took 16.7 months (MDUF/\ go<~! 75 days). In 2014. the average rE>view 

time for a 510(k) was 6 months (MDUFA goal 90 days), and a company 5ubm1tting a 510(k) had just a 22% chance of getting 

1t cleared with Ill the 3 month target, <Jnd a 61% ch<~nc8 of gett1ng 1t cleared within 6 montns. 

c. Moreover, many programs that were Implemented to exped1te the rev1ew and approval of certain classes of novel products 

(rare and diseases for which there are no other therapies or s1gn1ficant unmet medical needs) would not be needed 1f the FDA 

met the target rev1ew t1mes in PDUFA and MDUFA 

2, If Congress conducted proper oversight of the FDA, the safety and effectiveness standards for drug and dev1ce approval, as 

wei! as the reasonable assurance of safety and e<ffectiveness standard and least burdensome approach for rnedKa! dev1ces 

would be appropriately followed. The FDA has moved away from approving drugs and b1o!og1cs that are- as stated 1n the 

regulations* "safe for use under the cond1t1ons prescnbed, recommended. or suggested in the proposed Jaoe!ing'' on the basis 

of clinical trials that demonstrate act1vity 1n import<~nt d1sease parameters (dmical act1v1ty in ame!ioratmg d;sease signs and 

symptoms, surrogate endpoints, and biomarker responses) in favor of endpoints like MaJor Adverse Cardiac Events (MACE) 

rmd surv1val. Moreover, in pract!Ce. the FDA has replaced the safgty and Gffect1veness standard with "climcal benefit" go1no so 

far as to tel! sponsors wh~eh indications for use the FDA deems appropriate as opposed to reviewing climcal studies and data 

for the claims that sponsors endeavor to develop. This iS not how the laws arC' written or intended. The standards for FDA 

approval have become more onerous re-sulting m longer and larger c!in1cal tri<~ls, which prevent and delay important medicines 

and devices from read11ng patients, (continued on pg. 3) 
161 

Ml 3 Alert 

Medical Innovation Impact lnc-J~?x 11/30/15 - Report #7 -Page 3 

Potential Posttive Impact on Innovation (continued from pg, 2) 

The law IS very clear regarding the ev1dent1ary sta11dard for drug approval - "the term "substantial ev1acnce" means "evidence 

consisting of adequate and we-ll-controlled mvestigat1ons, includmg clmical mvest1gat1ons, by experts qualified by scientific 

training and experience to evaluate the effect1ve-ness of the drug involved, on the basis of wh1ch it could fa1rly and responsibly 

be concluded by such experts th<lt the drug will have the effect 1t purports or is represented to have under the cond1t1ons of 

use prescribed, recommended, or suggested in th<? labeling or proposed labeling thereof" (FD&C 505- 21USC 355(d)7)." 

Substantial evidence does not refer to clmlc<ll benefit or survival or other disease outcomes, rather to conducting <'ldequate 

stud1es from which to conclude th<>t the purported effects are real ;;~nd reliable. 

a. Indeed, if Congress exercised proper oversight to enforce review times and standards of safety and effectiveness, it would 

not have been necessary for them to pass more laws ushering-In the rapidly~expandmg series of regulatory incentives for 

n1che carve-out areas of "high unmet med:cal need" w1th such programs as Fast Trdck, Pnonty Review, Breakthrough 

Therapy Designation (BTD). dnd Qualified Infectious Disease Products (QIDP), pediatnc exclusivity. and Rare Ped1atnc and 

Tropical Diseases Prionty Rev1ew vouchers. 

3. If Congress conducted proper oversight, issues that anse m the rev1ew of new products would be properly adjUdicated. 

Sponsors have the abil1ty to challenge FDA reviCwers through the FDA Ombudsman. however, the Ombudsman does not 

report to the commissioner, rather, the Center for Drugs Evaluat1on and Research (CDER), Center for B1olog1cs Evaluat:on and 

Research (CBER), and Center for Dev1ces and Rad1olog1cal Health (CDHR) each possess a separate ombudsman who reports 

to the center d1rectors. If the ombudsmen reported to the comrnissionGr and made regular reports to Congress as part of 

oversight, the FDA would be less likely to change approval standards, ignore prior agreements with cornpanies on the clmical 

stud1es required to demonstratl2' safety and effectiveness, and would be less likely to request Information during rev1ews that 

extends the review time llm1t, all of which would increase the certamty, consistency, and t1metiness of new product reviews, 

which are the intended effects of the laws 

4. If Congress conducted proper oversight of the Advi$ory Committee process for new drugs, biologics. and devices, experts m 

the med1ca! fields of study would bE' required to rev1ew new products. However, often, tre FDA does not include several or any 

physicians who treat the disease under review. "For the purpose of providing expert se~cnUfJC advice and recommendations to 

the Secretary (secretary of HHS Heo.!th and Human Serv1ces) regarding a dm1cal mvesi!gat1on of a drug or the approval for 

marketmg of a drug under section FD&C 505 or sect1on 351 of the Public Health Serv1ce Act, the Secretary shall establisf1 panels 

of experts or use panels of oxperts ... " The statute goes on to say,' members who are qualtf1ed by tra1mng and expenence to 

evaluate the safety and effectiveness of the drugs to be referred to tile panel and who, to the extent feastble, possess skdl <1nd 

expenence m the development, IT'anufacture, or utt!izat1on of such drugs," and'' .two or more members who are specialists or 

have other expert1se in the particular disease or condition for wh1ch the drug under reVt6w IS proposed to be mdlcdted," If 

experts were 1nduded on oands routtnely, the tmportance of fmd1ngs from clin1cal stud1es would be better appreciated, 

labeling recommendations would be more clinically relevant, and more drugs and dev:ces would reach pat1ents sooner. 

Unmtended Consequences (continued from pg. 1) 

SectiOP 7368.-21 USC 379h-2] and MDUFA (FD&C Section 738A.- 21 USC 379H). However, the reports are very difficult to 

interpret and have little grounding in the rea! world metrics that Congress requestod. As former FDA rov1ewer Henry Mt!ler 

pomted out· 

I was struck by the dissonance betwt;;en a statement by (FDA Commissioner) Dr. Hamburg several years ago and the FDA's 

performance where it counts-getting new medicines to patients. She bragged that "[p]reliminary results of reviews completed 

during FY 2070 indicate th,1t FDA hus the potential to meet or exceed almost all (71 of 72) FY 2010 review performance goals " 

But 2010 was the worst year for drug approvals m a quarter century This kmd of disconnect is typical of not only FDA but of 

other federal agencies: They create easify~met performance m11estones that may have littfe rel<1t1onship to the agency's actual 

mission. !nvokmg the old medicu! cliche. the operation was a success but thf' patient died. 

Take for exampk the way rev1ew t1me IS counted. The eegu!at1ons call for non-pnonty NDA's (New Drug Approvals) to be 

conducted Wtthm 10 months. However. 1n reports to Congress, the FDA counts rev1ew tnne tn "rev1ew days" not cnlendar d<1ys, 

whereby the fDA stops ancl starts the rcv1ew clock at 1ls dtscrotton, tyo~eally requestn-.g that sponsors answer questions that 

emerge 1n the revtew of new products by submttttng PMA, NDA and BLA amendments, wh1cr: then extend the review penod. This 

has the effect of increasing the percent of app!icattons reviewed wtthin target dates defined in PDUFA and (continued on pg. 4) ... 
162 

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Medical Innovation Impact ir'ld,:.:x 11/30/15 ~ Report #7 ~ Page 4 

Unintended Consequences (contmued from pg. 3) 

MDUFA and reported by the FDA to Congress, making performance appear to be withm (or close to) review period goals, even 

when, on a calendar basis, review times far exceed the statutory targets. Also note that the FDA reports performance m median 

rev1ew times; average review t1mes are calculated by outs1de and!ysts. 

The laws that Congress passed do not say that reviews should be conducted within a certain number of rev1ew days, rather they 

state periods of time (months for drugs and biologicS and days- not "rev1ew days"~ for devices). Moreover, the FDA reports 1ts 

performance m med1an review days, not average rev1ew days. Apparently, Congress did request that the FDA report the average 

number of days, but the average rev1ew time has not been adopted by the FDA as the primary measure. And, the FDA does not 

report average review t1me performance on a rolling ongoing basis 

As stated in the 2014 MDUFA Performance Report. FDA committed to report llle average total time to final decismn once 

deCISions were made for 99 percent of the PMA cohort and 95 percent of the 510(k) cohort FDA has made decis;ons on 98 

percent of the FY 2073 SIO(k) cohort and the average total time to decision is 726 total days, Currently, FDA has made decisions 

on 73 percent of the FY 2073 PMA cohort, 76 percent of lhe FY 2014 PMA cohort, and 58 percent of the FY 2014 570(k) cohort 

and cannot yet report average review times. Once the required percentage of each cohort has received a deCision, FDA \Viii 

report the average time to fmal deCISIOn m future reports 

Even when Congress performs some degree of overs1ght- der>1and1ng performance reports, for example- 1t does not msist on 

receiVIng a clear accounting of performance based on discrete measures that 1t desires to rev1ew. This has s1gn1ficant unmtended 

consequences poor oversight g1ves the appearance that the FDA is performmg wellm 1ts miss1on to promote health. w"len tt 1s 

not Absence of transparent mformation 1s one th1ng, acceptmg m1sleadmg Information IS qutte another. And, Amencans are not 

served well by either, As Walter J. Olesz.ek of the Congress1onal Research ServiCe explains 

Woodrow Wilson, in his 1885 classic t11fed Congressional Government, declared that Congress informing function ''should be 

preferred even to its legislative [lawmaking] function." He exptamed.· Unless Congress have and use every means of acquainting 

itself with the acts and dispositions of the administrative agents of government, the country must be helpless to learn how it is 

bemg served; and unless Congress both scrutinize these things and sift them by every form of discussion, the country must 

remam in embarrassing, cnpplmg Ignorance of the very affalfs which 1( ;s most Important tt should understand and dtrect. 

Redundant and Conflicting Laws: 

Because the first mcllnatJon of lawmakers to pass laws rather than to perform oversight, many new laws are redundant With laws 

that have been passed previously, and co'lflict With pnor laws· 

l. Cons1der FDAS!A (!=ood and Drug Admm1stration Safety and lnnovat1on Act) that reauthonzed PDUFA in 2012, One of the key 

provisions of this law was Breakthrough Therapy Designation (BTD), a program to expedtte the rev1ew and approval of a drug 

that treats a serious condition AND, 1f approved, would prov1de a s1gn1f1cant Improvement m safety or effecl1veness. Lookmg at 

the GUJdancG Document on Expedited Programs for Senous Cond1t1ons • Drugs and Biologics, one is hard pressed to see how 

BTD added to the other programs that were already 1n the law to accomplisr- th1s. :ncluding Fast Track [Included i.., the 1997 

PDUFA reauthorization called the Food a:--d Drug Administration Modernization Ad (FDAMA) of 1997], Prtority Review (mcluded 

m t'1o 1992 Prescription Drug User Fee Act), and Accelerated Approval (FDASIA 2012). Moreover, many products have been 

g1ven several of these designations, and Orphan Drug Des1g"'at1on, as wet! (see Esbnot- perfen1done, Opdivo- n1volumab, 

and Xalkori- ceritinlb): in fact 56% of novel products approved m 2012 qualified for multiple expedited programs, thereby 

demonstratmg the red;_.ndnncy and lack of need of BTD, These programs are very redundant. both 1n substance and sp1nt. If 

Congress knew the contents of the law by performing proper oversight these laws would not have been passed. DeficienCies 

m the implementation of Prionty Rev1ew, for example, could easily have been addressed m oversight, rather than 1n two 

major laws that ushered-m Fast Track a•1d Accelerated Approval. And, 1f the law needed to be twea~ed subseque"t to the 

acknowledgement of deficiencies m the ongmal statute that came to light dunng actual implementation, subtle amendments to 

Prionty Review could have sufficed. (contmued on pg, 5) 
163 

Ml 3 Alert 

Medical !nnovat1on !mpact lndt-·:x 

Unmtended Consequences (continued from pg. 4} 

Comparison of FDA's Expedited Programs for Serious Conditions 

Nature of 

program 

Reference 

Qualifying 

criteria 

Fast Track Breakthrough 

Designation 

• Section 506(b) of the 

FD&C Act, as added 

by section 112 of the 

Food and Drug 

Administration 

Modernization Act of 

1997 (FDAMA) and 

amended by section 

901 of ilie Food and 

Drug Administration 

Safety and Iru1ovation 

Act of 2012 

(FDAS!A) 

• A drug that is 

intended to treat a 

g:rious_s:QD.~l!-.i_q_n 

AND nonclinicat or 

clinical datu 

demonstrate the 

QQt~_\J!i!IJJ.9_!!9_QI~~ 

unmet medica! need 

DR 

• A drug that has been 

designated as a 

qualified infectious 

disease product" 

Therapy 

Designation 

• Section 506(a) of the 

FD&C Act, as added 

by section 902 of 

FDAS!A 

• A drug that is 

intended to treat a 

~eJj_0_\!~9Jlilitioil 

AND preliminary 

clinical evidence 

i~dlca-t~-th~-t ·th~ drug 

ITl..JlY \"l_t~JD.QI!f!.riJ.t~ 

substantial 

!.!Dprovement_Qj!J! 

£!iDigfu2igni ficacy! 

endpoint{s) over 

~vailaQl~~~ 

Accelerated Approval 

Approval Pathway 

• 21 CFR part 314, subpart H 

• 21 CFR part 601, subpart E 

• Section 506(c) ofilie FD&C 

Act, as amended by section 

901 ofFDAS!A 

• A drug that treats a serious 

condition AND generally 

provides a !Ill<i!!liJl&fu.l. 

advantage over available 

!h~;r_<!pic_~ AND 

demonstrates an effect on a 

~.!!Qg_<!l~J~!NP.:QiO! that is 

rea.sonabiy llkely to predict 

flip.ical benefit or on a 

~Jilli.£~.L~ndpoint that can be 

measured earlier than 

lrr~versible morbi.lli!.yQr 

mQD:!!lil.YlL_\tMJ iliat is 

reasonably likely to predict 

an effect on IMM or other 

clinicnl benefit (i.e., an 

intermediate clinical 

endpoint) 

11/30/15 - Report #7 - Page 5 

Priority Review 

Designation 

• Prescription Drug 

Lser Fee Act of 

1992 

• An application 

(original or 

efficacy 

supplement) for a 

drug that treats a 

serious condition 

A!'.'D~if 

approved, would 

provide a 

significant 

improvem&!l-!.i!] 

safety _ _g.r 

~ffec.ti.Y~IJ.~j OR 

• Any supplement 

that proposes a 

labeling change 

pursuant to a 

report on a 

pediatric study 

under 505A b OR 

• An application for 

a drug that has 

been designated 

as a qualified 

infectious disease 

product" OR 

• Any application 

or supplement for 

a drug submitted 

with a priority 

_ .. re':\~"'.'..v9~.S:!J~rJ_ 
164 

Ml 3 Alert 

Medical Innovation Impact !ndt:x 11/30/15 ~ Report #7- Page 6 

Potential Negat1ve Impact on Innovation (continued from pg. 1) 

reacttons wtth medtcal products. Recently, calls for Congressional hearings on surgiCal meshes, ir.trautenne devtces for btrth 

control, and endoscopic eautpment that spread antibtotiC resistant infection have been made. There have been many high 

profile hearings on drugs, tncludtng antidepressants, Vtoxx. Rezulm, and Avandta. In all of these, the FDA is bastcally accused of 

Inappropriately approving products that are unsafe. Of course, the issues are not so cut and dry. However, thts kind of overstght 

greatly damages the cause of med calmnovatton: 

As ear~v as 7974, FDA Comm:ssmner Alexander M. Schmtdt sa1d: "In all of FDA's history, I am unable to find a smglc mstance 

where a congresstonaf commtttee investfguted the failure of FDA to approve a new drug. But the number of t1mes when 

heanngs hiJve been held to critictze our ilpproval of new drugs have been so frequent that we iJren't able to count them. The 

message to FDA staff could not be clearer." In other words. no problem as long as thu Victims are mvis;b/e 

Faced with CongressiOnal overstght that seeks to blame the FDA when toxiCitieS emerge from the use of new products that have 

been approved, the FDA does three thtngs: (1) it retre~ches and shifts tts emphasis to a significantly disproportionate reliance 

on pre~approva1 requirements, as opposed to postmarket controls. thereby adopting a "protect health" posture at the exptmse 

of its ·'promote health" mandate, as defined in the law; (2) 1t re-states statutorily-defined approval standards for safety and 

etfect1veness (based on substantia! evidence that the drug Will have the P.ffect it purports or Is represented to have under the 

conditions of usc prescribed. recommended, or suggested m the labelmg submitted for rev1ew by sponsors) to unequivocal 

clmical utility and clinical benefit (as defined by the FDA. not sponsors), as well as to surviVal and disease outcomes: and (3) it 

seeks to limit the populat1ons for which new drugs are approved to treat, hence. the unprecedented rise m orphan drug 

designations- two hundred n1nety-one 1n 2014- and approvals for n1che specialty claims m recent t1mes. These three act1ons 

reduce the likehhood that the FDA w1ll be nd1culed m the future for toxicities that may occur With the use of approved drugs. 

But, they severely hmder the development of new products that may be of great help to patients. 

The case of Avandia, a diabetes med1cat1on, 1s particularly illustrative· (1) a Ne.w England Journal of Mcd1dne publication of a 

pooled study meta-analysiS revealed an mcreased l1kelihood of Sl9fllflcant cardiovascular toxtcJty m patients taking the drug; (2) 

the FDA restricted the drug's use m response to pointed critiCISm at a Congressional heanng; and (3) the FDA removed the 

restncttons from the label when the drug was later shown not to cause increased curd1ovascular problems, followmg a re-analySIS 

of a very large study. But the damage was done the FDA changed the regulations to requ!re larger and larger clin1cal tnals and 

disease outcome endpoints for products that are mtenaed tor large chronic d1seases. like diabetes. Knee-Jerk oversight tnggered 

by a flawed analysis had severe unintended consequences. 

A study led by Dr. Steven Nissen of the Cleveland Clinic linked Avandia to a 43% increased risk of having a heart attack and a 

64% mcreused nsk of death due to heart disease. The fmdmgs, based on data poofcd from 42 small ci!mcal tnals, were 

published in the prestigious New England Journal of Medicine 

Those results prompted some experts to question how wet! the FDA was monitoring the safety of prescription drugs. Just a few 

years earlier, the federal agency withdrew it<::. approwJ! of the painkiller Vioxx after evidence emerged thot it doubled the rrsk of 

heart attacks and strokes. When the critique of Avandt<J emerged, three tnd]or congressional comm1ttees announced their 

mtent10n to invest1gatt.\ 

The FDA responded by addinq warning labels to Avandh 

A new analysis th1s year by an FDA adv1sory panel suggested the in1tial concerns about AvandJ~J were overblown. Members of 

the panel potnted to design flaws in Nissen's study and sawl thetr evaludttnn found no ev1dence that tile drug made patients 

more vulnerable to heart attacks or other heart problems 

The m:tia! 'signal of increased nsk of heart attacks" reported by Nissen m 2007 has not been confirmed, the FDA sa1d m the 

statement 

As a result, the FDA will no longer require doctors to !imtt Avandh1 prescnptions to certain patients. Its new !abe! will likely state 

that anyone w1th Type 2 diabetes can use the drug m combination wtth diet and exerose to control thcv blood sugar, the 

agency said. 

Attacks on the FDA ut Congressional hearings due to the Avandia rre':<J-unalysls data, thdt were shown to be erroneous later. 

The report, by Sens Max Baucus (0-MT) and Charles Grass!ey (R-IA), concluded that there are "serious health risks associated 

With Avandia." It also criticized the structure of the FDA. particularly the fact that those who make deCisions about drug 

approvals are the same experts who must later oversee drug safety. (continued on pg. 7). 
165 

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tv1edlcal Innovation Impact !ndex: 11/30/15 • Report #7 • Page 7 

Potential Negative Impact on Innovation (contmued from pg. 6) 

lntroducmg the CongressiOnal hearing, subcommittee cha1r Rep Rosa DeLaura (0-Cl) satd: "Th1s report poses several troubfmg 

questtons for th1s subcommittee Most obviOusly. If Avandta IS unsafe, how did It ever get on the market in the f~rst place? For 

that matter, why is it still on the market, nght now? And whcd does the case of Avandia tell us about the FDA's current abr/Jiy to 

conduct its drug safety responsibilities?" 

What does the FDA do when 1t IS attacked 1n this way- as stated above, it runs for cover and ratchets-up the pre-approval 

requtrements for drugs that are used c'ironical!y 1n large numbers of pattents and prefere"tlally approves drugs for niche diseases 

and conditions. Of great concern !S that the Pres1dent's nommee for FDA Commissioner, Dr. Robert Caltff. IS a fervent supporter of 

onerous approval requirements, wh1ch st1fle med1calmnovat1on 

Calrff's mdustry tres run deep. He worked closely w1th drug companies m the best possible way: convincing them to do lc1rge, 

expensive. and, for Duke. profitable cl!mcal tnals that helped prove the eftectwcness of ma}nr med1cmcs like Sanofi's P!avix, 

Merck's Vytorin, and Johnson & Johnson JNJ Xare!to But he has not been a pushover, ever, and his goal has always seemed to 

be to make sure that doctors and patients howe the best evidence possibfe for dec1ding what drugs lo give to pattents. He has 

not always been easy on mdustry. 

In 2008, after Steven Nissen from the C!eveh'tnd Clintc had openly criticized Avandia, the GlaxoSmithK!ine diabetes drug, he 

proposed a new standard for studymg diabetes medicines that would msist they be tested in c!mical trials involving thousands 

of pat1ents to see If they had any effect on heart attack rates. When Nissen menttoned the 1dea at an open pub!Jc meetrng, Califf 

was fast to back it. 

"!can't Imagine a situation, given whot we know now, other than a screenmg mechanism folfowed by some sort of tna! for the 

net nsk and bf..>nefit versus nsk," Ca!tff sa1d ut the t1111e 

Industry has hated these trials, argurng that they are preventmg new drabetes drugs from bemg developed. 

It can be fully expected that the FDA will contmue to move away from the safety and effectiveness standard and derrand 

outcomes and surv1val data routmely w1th the new leadership and tn response to other unfortunate med1cal tssues that will 

invanably happen with new marketed drugs as more and more expenence 1s obtained w1th the1r use. Dr. Califf was asked this 

d1rect question at the Senate HELP (Hei!lth Educat1on Labor and Pensions) Comm:ttee heanngs on his nomhation as new FDA 

Commissioner on November 19, 2015 

In one nom ted exchange, Warren asked Califf about the propnety of clearing ther<Jp!eS at such a rap1d rate, once again 

referencing Califf's ties to the rndustJy. "Your relatJonshtps also ra1se concerns about your motwat10ns," said Warren. "Do you 

agree with arguments to tower standards for FDA approval of drugs and devices?'' 

"!have never been a proponent of !owermg slandards for anythmg," Ca!df shot back "!have been m favor of raisrng standards 

tn no case would 1 argue to lower the standard. I think! have been sttwnch in that regard." 

Whe:1 the FDA, undcrst<Jndab!y does retrench and hes to protect itself by mak:ng the drug approval hurdles higher in response 

to public rtdicule and accusatiOns of poor job perforrrance hurled at them at Congressional heanngs, Congress does not do its 

job. It does not perforM the proper oversight to re~ms~ruct the FDA that 1ts miss1on is to promote health as defined in the statute 

("to promote health by promptly and efficiently rev1ewmg clinical research and taking appropriate> action on the marketing 

of regulated products in a timely fash1on"). Through oversight. Congress doesn't re·d1rcct the FDA to uphold safety and 

effectiveness as the standards for approval, and reinforce least burdensome approach (for dev1ces). And, Congress actually a1ds 

the FDA m preferring to approve drugs for n1cne d,seases at the expense of d1scases that affect large populat1ons of pat1ents by 

passing laws !1ke FDASIA (Breakthrough 1hcrapy Oes1gnat1on) and 21st Century Cures (Pnonty Rev1ew for Breakthrough Dev1ces 

and many other provisions), which largely focus on orphan cond1t1ons, those affecting less than 200,000 patients per year. 

And so, the vicious cycle: (1) external events, such as the errergence of public r.ealtll cnses (ebola, H!V, methlclllm·resistant 

staphy!ococcal1nfections) and adverse events of approved products call 1r.to question the adequacy of FDA's approval pollCJes; 

(2) poor CongreSSIOn<~l oversight (publicly f)umilmtlllg the FDA when products are associated w1th undes1red events); (3) FDA 

retrenchment in the form of dispropo1 tionate focus on pre-approvn! requirencenb as opposed to post-approval vigilance, nnd 

red1rectmg efforts to spec,ftc areas at the expense of others; (4) lack of Congress1onal oversight to force the FDA to comport 

Itself m accordance w1th ongma! laws when the FDA understandably sh1es away from ;ts cJjrectlves to promote health, and (5) 

P<:JSsing of unnecessary ano controdictory laws ( nitiated a/o supported by the FDA) that cement the alternative approach the 

FDA has taken, which conflicts wtth Congress' ong1nul int8....,t. and stymie med1cal innovation. (continued on pg, 8) ... 
166 

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rvled1ca! Innovation Impact Index 11/30/15- Report #7- Page 8 

Potenttal Negat1ve Impact on Innovation (continued from pg. 1) 

The law provides for a balance between pre-approval hurdles and post-approval vigilance and makes clear that approval shoula 

not be denied m cases where quest1ons about a drug or device could be a'lswered in the post-approval setting via postmarket 

studies and controls. The law also permits the FDA to demand post-approval studies as conditions of approval, and after products 

have been on the market. Moreover. the FDA has broad powers after drugs are approved to exerCise enforcement by imposmg 

restnctions, revising Jabelmg, and execut1ng Injunctions and drug se1zures: it can also charge compan1es that do not comply w1th 

1ts d1rect1ves w1th m:sdemeanors (where H'tent need not be established) and fe!ontes. Therefore. sh1ftmg emph.as.s to 

pre-approval requirements 1s not needea 

a. 513(a)(3)(C)- ln making a detenninat1on of a reasonable assurance of the- effectiveness of a device for wh1ch an 

applicat:on under sect1on 515 has been subrn1tted, the Secreti:lry shall consider whether the extent of data that otherwise 

would be requ1red for approval of the applicatloG With respect to effectiveness can be reduced through rel1ance on 

postrnarket controls, 

b. 505(k)(3)(C)- ESTABLISHMENT OF THE POSTMARKET RISK IDENTIFIC/1. TION AND ANALYSIS SYSTEM- The 

Secretary shall, not later than 2 years after the date of the enactment of the Food and Drllg Administration Amendments 

Act of 2007, 111 collaboration With public, academic, and pnvate ent1tics- (i) develop methods to obtam access to 

d1sparate data sources 1nclud1ng the data sources specified m subpar<:~graph (C), (ii) develop validated methods for the 

establishment of a postmarket nsk identification and unalysis system to link and analyze safety data from multiple 

sources, with the goals of including, 1n aggregate- (I) at least 25.000.000 patients by July 1, 2010; and (II) at least 

100,000,000 patients by July l. 2012; and (111) convene a committee of experts, including individuals who are recognrzed 

1n the fteld of protecting data pnvacy and security, to make recom1T'endat1ons ::a the Secretary on the development of 

tools and methods for t'le eth1cal and sCientifiC uses for, and commun1c<lt1on of, postrnarketing data specified under 

subparagraph (C), inclut!mg recommendations on the development of t)ffectiVe research methods for the study of drug 

safety questtons 

c_ SOS(o)- POSTMARKET STUDIES AND CLINICAL TRIALS; LABELING: (3) STUDIE:.S AND CLJNICAL TRIALS.- (A) IN 

GENERAL-For any or all of the purposes spec1fled m subparagraph (B), the Secretary may, sub)Gct to subparagraph 

(0). reqUire a responsible person for a drug to conduct a post-approval study or studies of the drug, or a post~approval 

cilmcal trial or trials of 1:he drug, on the basis of sCientifiC data deemed appropriate by the Secretary, mclud1ng 

Information regarding chemically-re-lated or pharmacolog1caUy-related drugs. (B) PURPOSES OF STUDY OR CLINICAL 

TRIAL.-The purposes referred to 1n th1s subparagraph with respect to a post-approval study or post-approval clinical 

trial are the following: (1) To assess a known serious risk related to the use of the drug involved. (li) To assess stgnals of 

serious risk related to the use of the drug. (iii) To identify an unexpected serious nsk when available data indicates the 

potential for a serious risk, (C) ESTABLISHMENT OF REQUIREMENT AFTER APPROVAL OF COVERED APPLICAT!ON.-

The Secretary may requ1re a post-approval study or studies or post-approval clinical tnal or trials for a drug for wh1ch an 

approved covered appl~eat1on IS 1n effect as of the date on wh1ch the Secretary seeks to establish such requirement only 

1f the Secn:tary becomes aware of new satety Information. 

d. 505 (p)- RISK EVALUATION AND MITIGATION STRATEGY: (1) IN GENERAL-A person may not mtroduce or 

de!lver for mtroduction mto mterstate commerce a new drug 1f-(A)(1) the apphcat1on for such drug 1s approved under 

subsection (b) or (J) and IS subject to sect1on 503(b); or (II) the application for such drug approved under sect1on 351 

of the Publtc Health Serv1ce Act: and (B) a nsk evaluation and m1t1gat1on strategy is required under section 505-l with 

respect to the drug and the person fails to mairtam compliance w1th the reqUirements of the approved strategy or with 

other requirements under sect1on 505-1, 1nclud1ng requirements rcgard1ng assessments of approved strategieS. (2) 

CERTAIN POSTMARKET STUDIES.-The failure to conduct a postmarket study under sect1on 506, subpart H of part Jl-1. 

or subpart E of part 601 of t1tlo 21, Code of Federal Regulations (or any successor regulations). IS deemed to be a 

violaton of pari'lgraph (1). 

Proper Congressional oversight IS essential to demand that the FDA use post-approval controls 1n lieu of more onerous 

pre-approval requirements, The vicious cycle of 1mproper Congressional oversight IS responsible for the progressive deteriorQtion 

of the safety and effectiveness standard in deference to more onerous din1cal utility and disease outcomes and survival 

endpoints. (continued on pg. 9) ... 
167 

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Hedical Innovation lr·npact !nde.x 11/30/15 - Report #7- Page 9 

Potenttal Negatwe Impact on Innovation (contmued from pg. 7) 

A direct sequelae of this vktous cycle IS the nse of specialty pharmaceutical products, those tntended for small populations of 

pattents. The FDA, following public nd1cu!e in oversight heilnngs of drugs for dtabetes and arthntis, has imposed new standards 

for approval- not only must drugs for diseases that affect miltions of Amencans (diabetes, cardiovascular dtsease, COPD, obes1ty, 

etc.) prove clinical utility (as opposed to dtsease actiVItY as embod:ed in the effectiveness standard), they must be studied in huge 

tnals and either show an Improvement m- or no deletec1ous Impact on- survival and major adverse card1ac events. And. even at 

that, the FDA requires large and expensive post-approval studms to conf1rm the f1ndu1gs. 

The rDA has 1rr.posed a de facto "better than the Geatles" standard, as well, basically, 1f the drugs are not shown to be more 

effective or safer than drugs already on the market (In large trials usmg the "average pat1ent standard") the FDA denies their 

approvaL [This is very unfortunate because often, many pattents expenence berefit of a drug on an individual basis and the effect 

is lost when pat1ent responses are averaged over the entire study population.] So, compan1es have increasingly foregone the 

development of drugs for these diseases and focused on rare diseases and conditions for whiCh no other therapies exist. These 

qualify for Orphan Drug, Fast Track, BTD, Expedited Review, and Accelerated Approvu!, which provide substantial re~u!atory 

incentives (reduced review times, sm<1ller tri<:Jis, etc.). 

Add to that the: benefit of lower R&D costs. Derek Fetzer, director. global strategic ana!yt;cs/g!oba! strategic marketmg & 

market access. at .Janssen PflarmdceutJcdi Services, says /hal th1s made 1t worthwhile for a big fmn !rke J&.J to tndke a move mlo 

the speCially arena· "fmprovmg on the many good drugs on the market IS a stgruflcant, techntcal chaffenge. ··he observes. "ThiS 

1s because demonstratmg smaller, incrementtll benefits actua:ly reqwres more patlf!nts m a climca! study, from a stattsttcal point 

of vtew, and thus is more costfy. .. 

Compared to PCP-focused candidates. spec1afty medictne clinical development can be not only tess expenswe but offer a 

nearer-term opportunity for cashmg-in on an investment. SpeCialty med1cme candidates typtcafly are vetted by big pharma 

along the dtmensJOns of demonstratmg substantial mnovation, where R&D efforts can require fewer patients and Significant 

differences can be demonstrated over a shorter penod of t1me 

There are regufatory rewards, lao. The most prominent "X-factor" in new drugs-the FDA-displays more Jove tov.;ord products 

that asptre to occupy snhent treatment vo1ds as opposed to those gau1mg incremental yardage vs existmg therapy Indeed. this 

iCJ an essentiaf element of FDA's chdr"ter 

"One central factor FDA takes into account in dctcrminmg thr: speed of review of a new product application is whether it 

addresses an unmet med1cal need, hence potentially translating mto shorter t1me to market," says Wayne Pmes, former FDA 

assoct<Jte commissioner, who is now president of regulatory services and hea!ihcare for APCO V'lorldwide. "'A usual review is 10 

months and a fast~track or pnonty rev;ew ;s six months or less." (continued on pg. 10) ... 
168 

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'-1edica! !nnovCJtion Impact index ll/30/15 • Report #7 - Page 10 

Potent1al Negative Impact on Innovation (contmued from pg. 7) 

Another upshot of Congress not performmg appropnate oversight 1s the passage of an ;ncreas1ng number of laws, many of WhiCil 

are redundant. Ne1ther the FDA nor mdustry can keep pace. The fact that the 21st Century Cures Act includes prov!slons for tramn•g 

FDA rev1ewers on least burdensome approach validates what many have observed over the last several years m dealing with FDA 

rev1ewers due to great turnover <~t the agency, new rev1ewers are not knowledgeable of the law, especially the fundamental 

bedrock groundmg principles of the law. Rather. they are tra1ned, w1th other personnel, on the new laws that Congress passes 

And, because of the new and chang1ng lAws and difficulties m dealing w1th the FDA, industry tS spendmg rnore on regulatory affatrs 

A 2012 study found that: 

Top 50 pharmaceutical companies have increased the1r regulatory affairs budgets by an average 27% since 2070. Smaff drug 

manufacturers, as well as med;cal dev1ce compames, also mcreased thetr regulatory affa1rs budgets dunng the same t1mefrume 

J'FDA La;;., provides a 

i balance between preapproval requirements 

and postmarket controls 

' Balance between prew 

1 approval requirements I and postmarket 

! controls is lost as the ! vicious ~v.cle ~~rns 

Pre-approval 

requirements 

Recommendations (continued from pg. 1) 

Pre-approval 

requirements 

Postmarket controls (studies, 

Vigilance, surveillance) 

Postmarket controls (studies, 

Vigilance, surveillance) 

<' • Pre-approval drug, biologic, and device studies 

longer, larger, and more expensive 

Race toward niche dalms and regulatory incentives 

{Orphan Drugs, Breakthrough Therapy, Fast Track, 

Priority Review, Accelerated Approval) 

Postmarket requirements remain, with c!awback- if survival 

and disease outcome endpoints not met, can remove from 

market even if still "effective" 

Fewer approvals of drugs affecting diseases that affect millions of 

Americans- !ess innovatwn where it can have the most impact 

with the observation that "administr<ltton of a statute IS, properly speuking, an extension of thC' legislative process " 

Oversight. in brief, 1s crucial to the lawmakmg orocess Only by mvasttgating how a law 1s bemg admmistered can Congress discover 

defiCienCies m the ongma! statute and make necessary adtustments and rcfmemcnts. As a Senator stated, "We must do more than 

write laws and dectde policies. It is also our responsibility to perform the oversight necessary to insure that the administrution 

enforces those laws as Congress intended·~ 

But, Congress had not been exercism9 "contmuous watchfulness" with respect to FDA m rts 'nrssron to promote health through the 

revrew and approval of new mt>d1c:a! pcoducts. 

Notwithstanding Jarr:es Madison's words regMding the power of the purse rn Congressrona! oversight. Congreo.s does not 

effectively w1eld th1s power prirCJpal!y bc:cause only 55% of the FDA IS funded by taxpayer dollars. Approximately 45% of FDA's 

2016 budget of $4]t1 bi!11on 1s pard for through user fees; for fiscal year 2016, the user fee<> mctude $2,3711,200 for an NDA (New 

Drug App!icatton), $261,388 for a PMA (Pre-Market Approval Application) and BLA (81o!ogics L1cense Appl1caUon). and $5.228 per 

510k. It appears that Congress has relinqu1shed overs1ght to the bropharma and med1cal device indJstnes, (contmued on pg, 11) .. 
169 

Ml 3 Alert 11/30/15 - Report #7- Page 11 

Recommendations (contmued from pg. 10) 

however, fear of tne FDA and of repercussions from publicly cnt1cizing the FDA render this form of oversight 1neffect1ve. But, 

PDUFA and MDUF.A. have definite performance targets for FDA The problem has been that Congress has allowed the FDA to 

produce 1ts own scorecard and set its own objectives w1th respect to PDUFA/MDUFA goals, which do not accurately portray FDA 

performance. Therefore. w1th respect to user fee re-authoriLation, we recommend the fo!lowmg 

1. A Government Accountt~bd1ty Off1ce (GAO) 1nvest1gation of FDA performance with respect to review t1mes under PDUFA/ 

MDUFA, accountmg 1n calendar days. This would 1nclude anonymous ,ndvstry surveys that would ferret-out the appropnatoness 

of FDA rev1ew day determmations (based on major deficiency letters and amendments to new product applications and other 

mechanisms that extend the rev1ew clock). The GAO would also be asked to prepare a standard report template for FDA 

performance parameters th<-1t IS comprehensible and grounded 1r1 real-world metrics, for example, calendar days. 

2. 2017 User F-ee Reauthonzat1on provisions· 

a. As a cond1tlon of the legislation. Congress should Withhold FDA PDUFA and MDUFA funds unt!l NDA, BLA, PMA and 510k 

performance targets are achieved. Alternatively, compan;es could be refunded for applications that are not rev1ewed within 

target time frames (l% reduction m user fees per d<1y exceedmg rev1ew penod l1m1t. For small companies, a transterrub!e tax 

credit of $10,000 per day of delay.) 

b. The FDA should be reqL>ired to make yearly reports to Congress on review t1me performance ;n calendar days, and, 

Congress should conduct yearly heanngs on FDA performance, 

c. Quarterly reports to Congress by the FDA ombudsman's office (which should report to the Commissioner, not to the FDA 

center directors) regarding gnevancos that have been raised by companies in the FDA review of their products. Perhaps, if, 

as u matter of law, Congress were mnde <:~ware of problems us they occurred. proper oversight would follow. Also, this would 

protect industry from FDA repercussions 

Unfortunately, proper oversight, alone cannot make-up for the problems that have been caused because of the lack of effective 

Congressional oversight for many years, ·r herefore. other provls,ons must be Included 1n the user fee reauthorization to essentially 

re-set the FDA on the foundations tiMt were established pnor to the user fee era 

1. Restatement of promoting health as the FDA's pnnopal funct;on w1th respect to new products. The law states the fo!low1ng as 

the FDA's miss1on- "to promote health by prornpt!y and efftctently rev1ewmg c!in1cal research and taking appropnate actton on 

the market1ng of regulated products m a t1mely fashlo'l." Of course, protoctlllg health 1s part of promotmg health, however, the 

FDA has elevated "'protccttng" health as its mam rn;sston. Promotmg and protect1ng health are two different postures- the 

latter looks to preserve that whtch currently extsts while the former engenders opt1rntsm ar;d belief in the advancernent of 

se~enttf1c discoveries as a r1eans of 1rnprov1ng the health of AMencans. ImpliCit m promotmg health 1s an understandmg that 

occastonally new products may not be found to be as desirable as we would like them to be. however. the only way to have 

genwne progress is to acceot and deal w1th ·'bleeding edge" issues as we try to onng c1...ttmg edge treatments and d1agnost1cs 

to patients as soon as posstble. The law 1s actually biased toward embrt~cmg medica! 1nnovat1on by assuming that new drugs 

that undergo the drug development gauntlet would be approved, unless the drugs (or applications) had certain deficiencieS 

~see 21 USC 355(d) Grounds for refusmg application, approval of (1pplicutlon; "substuntin! ovidence" defmed]. This attitude <:~nd 

inclination is not embodied in many FDA regulations and guidance documents, as WE'll as m new sections of the law thflt have 

been passed as part of reauthonzat1on legislation. The law a!so prov:des for a balance between pre-approval hurdles and 

post-approval controls and makes clear thnt approval should not oe denied in cases where questtons about a drug or device 

could be a~swered m the post-dpproval settmg Vl<'l postrnarket controls (studies. vigt!nnc:e, and surveillance). 

2. Restatement of safety and effectiveness as the only requ1s1te standards for i'lpproval of new products. (For devices, 

reaffirmation of reasonable asst.rance of safety and effectiVeness. and le<Jst burdensoMe approach 1s needed.) Leg1slat1on 

needs to explicitly state that effectiveness to be evaluated by the FDA 1n accordance w th the labeling proposed by the 

sponsor and that the FDA 1s not to 1m pose standdrds requiring demonstrat1on of dtniCal utiltW for approvaL The FDA can and 

should limit the claims based on tho data - if there are no cl1nica! benefit data in the appl!cat1on, then clinical benefit should not 

be cla1med. Likew1se. legislation that expliCitly hsts <~Cceptab!e measures of effgctlvRnE><;<; that c;m support approval -

pharmacodynamics effects on d1sease parC'irneters, chntcal sign~ and symptoms, b1ornarkers. surrogate endpoints. patientreported data, comparative effect1vcress, chmcal outcomes, and sL.rvival. A strong caveat that cor1Parat1ve effectiveness, 

survivaL and disease outcomes are not needed to demonstrate ef~ectiveness, but are needed to obtam da1ms that include 

these parameters is needed. The legislation should also state the upproved lAbel will contain the (continued on pg 12) 
170 

Ml 3 Alert 

Hedical !nnovat1on Impact Index 11/30/15 ~ Report #7- Page 12 

Recommendations (conttnued from pg. 11) 

measures used to determine effectiveness and da1ms w1!1 be limited to the spec1f1C fmd1ngs. The rDA can be perm1tted to establish 

categories of approval accordmg to thG nature of the ev1dence used to support effectiveness, and if sponsors so des1re to obtair 

additional. "higher order,'' categories (for example, survival and disease outcomes), supplemental approvetl appl1cat1Dns can be 

submitted. 

3. Provisions for Breakthrough Therapy Designation, Accelerated Approval, Fast Track, Pnority Review and Accelerated App(oval 

should be rescinded -w1th enforcement of the effect•vo-ness standard defmed 1n #2 above and w1th the FDA meeting its review 

time framGs these programs w;!l no longer be needed. (Orphan Drug designation and OIDP should rema1n.] 

4. Post-approval studies should be l1m1ted to amassing greater safety databases to 1nform labeling. Stud1es performed to 

generate ev1dence for higher order effectiveness cla1ms shall not result m market Withdrawal ,f h1gher order effectiveness 

object1ves are not met. This is in contrast to the current regulations. wh1ch allow for rescmdmg product approval if drugs 

approved on the basis of surrogate endpomts are not shown to have Improved d1sease outcomes and survival In post-approval 

studies. 

5. Personalized med1cine in the real-world stwuld be fostered, as welL Leg1slat1on should make clear wh1ch decisions arc the 

domam of the FDA (publiC he<:~lth) and those that are tre dorna1n of phys1c1ans. pat1en::s, and other members of the medical 

marketplace ecosystem. The FDA 1s responsible for !>afety and effec:1veness. Clin1cal utility and climcal benefit often cannot br0 

easily measured or analyzed in "average patient studtes" because these can vary greatly from patient to pat1ent. If sponsors 

seek cla1ms that communicate clinical utility and clin1cal benefit, then, the sponsor must present data to the FDA that supports 

these da1ms m a meanmgful percentage of pEitlents, even 1f the exact profile of responding pat1ents cannot be defined for 

labeling purposes, either demographically or genettcally. To further foster personalized mcdtcme, the data from clintcal trials 

should be made available to pract1cmg physiCians who would then be able to query the databases to obtain knowledge of the 

effects of the drugs on potients gtven cert<11n demographic and genetic profiles. this wit! aid physicians 1n their pnvate health 

dec1s1ons, that IS, whether to liSe thG qrugs m real-world patients. 

Another recommendation 1s •or Corgress to refram from us1ng hearings as a venue to publicly embarrass and hum1!1ate the FDA 

when products that have been approved are shown to have undestrable effects and toxiCitieS when used 1n the real world m larger 

numbers of patients. This starts a vicious cycle that stifles mec.Jical innovation: poor oversight:> tack of overs1ght :>regulatory dnft > 

redundant and contradiCtory laws> poor oversight It also sets an expectC'Itlon 1r1 the eyes of the public for the FDA to be perfect 

when :t comes to the rev1ew and approval of new products. We should not be conditioned to expect perfection. rather, we should 

be assured that proper mechan1sms are m place to appropnately JUdge the safety and effectiveness of new products and to track 

them ond rap1dly report any 1ssues that rn1ght emerge after approval. The FDA should then act, appropriately, e1ther with rev1sed 

labeling or other acttons, mdudmg removal from the market m extreme settings. Congress would do well to reinforce to the pubhc 

that the FDA is JUSt one member of the med1cal ecosystem marketplace ~ phystcians, medtcal sociGttes, hospitals, cooperative 

research groups, drug compantes. and elm! cal researchers have an 1mportant responsibility to d1ssemmate Information quickly and 

to educate medical professionals and the public. PlaCing blame at the door of the FDA IS neither accurate nor conducive to 

fostenng rredicEII innovat1on. 

Accordmg to Mr. Oleszek: 

The rise of the admimstrative state (the plethora of federal departments, agencies, commissions, and boards) has produced u 

po!icymakmg rival to Congress. Administr~ltors do more than simply "faithfully execute'' the laws according to congressionul 

mtent (wf11Ch may be vague). Federal ayenctes are f1lled w1th knowlccigcable career <.md non-career spectaflsts who, among 

other things. write rules and regulations that have the force of law, enforce the rules via mvest1gations and inqumes; formulate 

policy initiatives for Congress and the White Houso; interpret statutes in ways that may expand their discretionary authonty or 

undermine legislative mtent; and shape policy development by "sel/rng'" their ideas to lawmakers and committees via the 

hearings process, I he issuance of agency reports, and in other ways. The large role of the executive branch, whose activities 

affect nearly every Citizen's life. underscores the en/leal role of oversight in pmtectmg the poi!CyrnaJong prerogatwes of 

Congress and holding administrative entities accountable for their actions and decisions. 

No government regulatory agency w1e!ds more power than the FDA, which regulates 25% of the US economy. It has amassed more 

and more power largely through the expandmg body of FDA law p.:=1ssed by Congress and regulations and guidance documents 

that 1t tssues. As we have seen with eac'l PDUFA and MDUFJ\ reauthori.;-:at1on legislation. passmg more laws does not change thl? 

behavior of the FDA~ only Congress1on<"ll oversight can ensure that the FDA comports itself with the letter (continued on pg. "13) ... 
171 

Ml 3 Alert ~ed\callnnovat1on Impact Index 11/30/15- Report #7 -Page 13 

Recommendations (continued from pg, 11) 

and Intent of the or;ginalluws. 

Congress must do a better job of FDA oversight if the scientific discoveries that are bemg mCJde at an accelerated pace are to be 

qu1ckly developed into products that cnn affect the lives of patients today. 

Address Inquiries to Joseph Gulfo, MD, MBA, Executive Director~ Rothman Institute of Innovation & Entrepreneurship 

~ jvgulfo~ci'fdu.edu 
172 

1/1012015 FDA 2014 approvals -the message behind the numbers) TlleHI!I 

January08,2015,1000am 

FDA 2014 approvals -the message behind the 

numbers 

ByJ<JSIIphV.Gulf<J,MQ,MBA 

The FDA provided an update on new drug approvals in 2014, stat1ng that as of December 15. thirty-five new drugs were 

approved, compared to 27m 2013. 

Here is the high level summary 

1 Fifteen of the 35 drugs were Orphan Drugs, the highest number since the Orphan Drug law was passed in 1983. 

2. Fifty-seven percent of the approved drugs had Priority Rev1ew tags 

3. Thirty-seven percent of novel drugs were on the Fast Track rev1ew route. 

4. The agency noted 11 clocked a shorter median approval time for expedited drugs, at 6.5 months in 2014 compared to 7.9 

months in 2013. 

By the end of the year. the FDA website stated 41 new drugs were approved, in 2014. 14 more than in 2013. Here's the rub 

-40 percent are for rare diseases. underscoring the industry's focus on spec1a!ized products, where compet±t1on is !im1ted. 

development is easter (thanks to the FDA programs, like Breakthrough Therapy Des1gnat10n), and annual prices often exceed 

$100,000 

The message to drug developers and patients could not be clearer -the FDA WI!! preferentially look at and approve the "no 

brainer'" applications, those that are intended for small populations. and for wh1ch no other therapies exist. no matter how few 

patients qualify 

This performance reiterates the FDA's continued fear-based approach to product review and approvals, despite its statements 

to the contrary and var1ous programs, like the redundant and superf1uous Breakthrough Therapy Destgnation pathway that 

1! cont1nues to tout. 

The Agency is very proud of this performance. and because of that, they will not change their p01nt of view or their 

poliCies. Problem recognition is the first step to change and reform. No one at the FDA seems to see the problem. Rather, they 

are celebrating this performance. 

W1th respect to pricing of these n!che therapies. drug makers and Investors see an Irresistible confluence of forces- the FDA 

making rt. very easy to develop niche products, Orphan Drug Designations validating that these indications are indeed rare. and 

the combination of the "Breakthrough" and "rare" labels commanding high pnces. Thus, achievmg profitability 1s made much 

Interestingly, 316.10(B)(ii) of the Orphan Drug Act states 

"For drugs intended for diseases or condrttons affecting 200.000 or more people in the Umted States, or for a vaccine, 

diagnostic drug. or preventive drug that would be giVen to 200.000 or more persons per year. a summary of the sponsor's basis 

for behevmg that the disease or condition descnbed 1n paragraph (b)(6) of thiS sect1on occurs so Infrequently that there is no 

reasonable expectation that the costs of drug development and marketing w1!! be recovered 1n future sales of the drug in the 

United States." 

The intent of the Act 1s to promote the development of therapies for rare diseases by offenng 2 additional years of market 

exclusivity. The rationale, of course, is because the rarity of the disease would render profitable commercialization impossible. 

That's not what Is happening with the new drugs that the FDA is approv1ng for rare diseases -very h1gh prices are mak1ng many 

products for these cond1t1ons ach1eve near blockbuster, 1f not multi-blockbuster. status 

Take, for example, cystic fibroSIS, a condition that affects 30,000 patients 1n the US and about "1,000 new patients per yeardearly, this is an Orphan indication. Yet, Vertex Pharmaceuticals is a $28.76 company, charging $300,000 per year for 

Kalydeco, a therapy for just a small subset ofCF patients, 

There is an UN-Holy Tnnity of FDA fear, which promotes the development of niche products. Orphan Drug designations, which 

command high reimbursement rates, and mvestor demands for predictable and steady growth that is turning our drug 

development companJes into niche product developers 

The Senate is about to add more incentives onto this triad. The Dormant Therapies Designation. wh1ch would confer 15 

years of exclusivity on new drugs and biologics for which there IS "one or more unmet medical need." This is the same 

language used in Breakthrough Therapy Designation, Fast Track Accelerated Approval, Priority Review. and Orphan 

Drug. This program would only prov1de further mcentJVes for the development of mche products at the expense of products that 

could help many patients. And, it IS perfectly consistent With the type of drugs that FDA IS preferentially approvmg, based on 

htlp"//thehlll.comlb!ogs/congress-blog/healthcare/228803-fda-2014-approvals-the-message-behind-the-numbers 112 
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1/10/2015 FDA 2014 approvals -lhe message beh1nd the numbers I TheHill 

fear. 

A healthy dose of common sense and perspective is needed to understand the perverse effects of these combmed forces 

The first place to start is the FDA, which needs to get back to promotmg health and stop putting labels, like "breakthrough 

therapy," on products. The FDA needs to do what it is paid to do- revtew and approve new drugs in a timely fashion. 

Instead ofthe sc1ence and medicine dnvmg the development of new products, FDA policies are domg so 

And, patients continue to suffer 

the author INNOVATION BREAKDOWN: How the FDA and Wall Street Cripple Medical Advances (Post Hifl 

and CEO of Breakthrough Medical !nnovatwns He has more than 25 years of experience in the biopharmaceutical and 

me<JJCal de''ice former CEO of MELA SCiences 

The !1;11 1625 KStreeL NWSu1te 900 Washington DC 200061202.&28.8500 !elj202-628-8503fax 

The contents orth1s site are ©2015 CapJ\ol H1!! Pub!1shmg Corp. a subs1d1ary of News Communications. inc 

http:l!theht!l.comlblogs/congress-blog!healthcaref228803-fda~2014-approvals-the-messagc-behtnd-the-numbers 212 
174 

9/13/2014 ww.,iv.washmgtontJmes com/news/2014/jul/11/gulfo-another-bandage-on-a-chromc-wound/pnnU 

CULFO: 'Right to try' just another bandage on a chronic wound 

·\lew 1mt:at1ves can't mask need for closer look at FDA 

ByJo>PphV Gul'ol/. ~ 

"Right to try" laws a1rn to broaden access to expenml?ntal drues fo1 people w!<o are te1·mmally ill Colo1 ado's law was enactc>d m anc1 m 

Lou1s1ana anr.J MiSSISSippi, the laws are wan1ng on the gowmms' stgnatures In Amona, nghHo-try will be put to rert:rendun' 

process, hE'Ip1ng to ensw·e 1:hat 

The FDA response IS at the heurt of tile proiJiern. NotiCe thC' commiSSioner's use ofthe wmd "protected 

they try1ng to p1 otect? The benef1t-to-nsk rat10 IS overvvhrln11ng!y fDVOt 0Ue m 

Sccuon 1003, Subpart 1 of the Federal Food, Dr11g, and Cosmt>t1t Ad'"""""""" 

effloently rev1ew1ng clinical I e<>earch and tak1ng app1 opr1ate action on the markct1ng of rrgubt<:>cl products m a wnely mannr1 " 

Oddly, th1s •S not what the FDA says about 1tself. Instead, the FDA wpbs1tc statPs: "Wh<'lt We Do. [The] FDA 1s 1 espons1ble for protectmg the puiJIK 

11Palth IJy assunng the Silfety, 1?'ff1ca(y and :;e(lHitY of human drld vercr:n,11 y drugs, b1olo81Ca! products, nted:cal df''JICes •· 

What about nll'>l<:>ad1ng the pubi1C In a 

fastc>r 1n the Umted States than1n 

that the statutory 1 equirem<o'nt 1s 

for FDA reform 

that can be freely mterchar.g('d, they represent completely different JdPolog1es. Protectmg sorvf's 

status quo It i'ISSunws cur1ent medi(I!W IS alwuys ~,<lfe, whPn that .soften not the case 

m FDA Vo1ce, thC' wmmiSSIOner touted the fact thar 111 201"3, the <'lpprova! times for drugs was 

The comrTHSSioner went on to l<~ud new leg1SIJt10n that was p,1ssed 11., july 2102 

new Breakthrough Therapy Designation Sir( e the ene~ctnH•nt of this pwce 

des1gnation and SIX products were approved 

date {as dpfmrd by PDUFA- Prescnpt10n D'ug User F1'e AU) 

The details about thiS product (Zykad1a) were not rn('ntloned 

mutat1on. whtch make up 5 percent to 7 percent of all non-small-cell 

sma!!numbcr 

As janet Woodcock, director of FDA's Center for Drug Evalur1t1on and Resea·cll, stated m May at a Friends of Cancer Research rneetmg. 

Breakthrough Thet apy IS 111tended for produns that show "\jWCtawlnr re'>ults·· and would ,. "Thr urcumstcltlres ,11 wlw h tlw, 

would most likely occur JH' tn niche scttL'lgs whc1 e thPre arc no altc•·nat;vc trcutmcnts 

positive 

34 percent of drugs rece1v1ng th1s rerlundant Cl'Fd superfluous des1gnat1on have been targeted cancf'r drugs. The u·awsty 1s thut th•s 

the others encou1 age drug makers to develop products for 5m<'Jll n!che cla1ms. 

http:/1'-WIW .washingtontimes. com/news/20 14fju !/11 /gulfo-a no!her -b a ndage-on-a-ch ro nic-wound/pri ntJ 112 
175 

9/13/2014 WM"i,washlngtontimes com/news/2014!julf11/gulfo-another-bandage·on·a·chronJC·WoundlpnntJ 

Rlght-to-Lry is the latest Band-Atd on the chron1c wound of FDA pedoJmancP Ba'1ri<lgc><; hdo1 e ·t that have fi'liled include PDUFA, MDUFA, 

Trw Jf'<Json fm fai!utP 1s bf'Cilll'">l' ncFle of them add1css the fundamental problem caus1n3 

As w1th chrontc wounds, when the fundamental m.:dical coqdJtiOn 1s not addresst'd, ampl.tatlon 1s the u"lfortunatc next step to save the p,'lttent 

joseph V. Gu/fo, MD., rs the autho1 of '"lnnovatwn Breakdown. How the FDA and Wolf Street Cupp!e MPdiCOI Advancr~N (Po>t Hill Press) and CEO of 

Breakthrough Medical lnnovauons 

http:I/W\'IW.washingtontimes.com/ncws/2014/jul/1 1/gutfo-another-bandage-on-a-chronic-wound/prin!f 212 
176 
177 

PRAISE FOR INNOVATION BREAKDOWN 

"Finally, a behind-the-scenes look at the mysterious and often poorly 

executed approvals process of the FDA. An important book for consumers, physicians, investors, and scientists---anyone who is interested in medical advances that can save lives." 

--JOSEPH PIERONI, retired CEO and President, Dniichi Sankyo Inc. 

"By focusing on the fate of one small company, Joseph Gulfo has 

written a riveting tale of how the FDA slows down crucial medical 

innovations, just when we need them the most. Policymakers on 

both sides of the aisle should absorb his prescriptions for fixing the 

system." 

-MICfiAEL lv1ANDEL, PhD, Progressive Policy Institute 

"Dr. Gulfo has written an important book that deserves to be read by 

everyone interested in having access to new medical treatments. The 

enormous and all too often insurmountable challenges in bringing 

breakthrough medical products to doctors are not unique to small 

biotech and medtech companies, rather, even the industry-leading 

firms struggle against these forces. And, in the end, it's the patients 

who suffer." 

-BRIAN l.EYLAND·)ONES, MD 

Vice President, Molecular and Experimental tvledicinc 

Avera Cancer Institute, Sioux Falls, SD 

"Finally, an incisive look at the path that medical innovation takes 

through the FDA, the courts and the public advocacy groups and 

the crippling effect it has on advancing new treatments to treat and 

diagnose disease. Today's regulatory/legal/public advocacy complex 

is stifling progress and killing medical breakthroughs. Joseph Gulfo 

lays out why this has happened, how to fix it and how to make all our 

voices heard." 

-NA:\CY LURKER, CEO, PD! Inc. 

"A fascinating read of the relentless challenges a passionate entrepreneur faced and overcame to bring a medical breakthrough to patients." 

-S\iSAN SCIIERREIK, 

l;ounding Director, Seton Hall University Center 

for Entrepreneurial Studies 
178 

INNOVATION 

HOW THE FDA AND WALL STREET 

CRIPPLE MEDICAL ADVANCES 

JOSEPH V. GULFO, MD,MBA 

MD, MBA Biopharma/Medicai Technology 

Entrepreneur and Investor 

A POST HILL PRESS BOOK 
179 

Innovation Breakdown 

How the FDA and \.Yall Street Cripple Medical Advances 

2014 Joseph V Gulfo 

ISBN (hardcover): 978-1-61868-957-3 

ISBN (eBook): 978-l-61868-958-0 

No part of this book may be reproduced, stored in a retrieval system, 

or transmitted by any means w·ithout the written permission 

of the author and publisher. 

Published by Post Hill Press 

109 International Drive, Suite 300 

Franklin, TN 37067 

Cover design by Ryan Truso 

Supplemental design by Travis Franklin 

Interior book design by Nemvirth & Associates, Inc. 

Visit us online at http://posthillpress.com 
180 

To Adele 
181 

Contents 

Introduction 

CHAPTER I 

I Don't Want to Fight Anymore 

CHAPTER 2 

From Star Wars to Skin Cancer 

CHAPTER J 

Innovation is Hard Enough 

CHAPTER 4 

FDA Part I: What's Supposed to ! Iappen 

CHAPTER 5 

FDA Part II: The Letter Bomb 

CHAPTER 6 

FDA Part III: Taking Matters Into Our Own Hands 

CHAPTER 7 

$160 Million The Hard Way 

CHAPTER B 

Let's Not Forget-This Machine Saves Lives! 

CHAPTER 9 

I Don't Want to Fight Anymore, Part II 

CHAPTER 10 

rihe Medical Innovation Manifesto 

Acknowledgments 

For More Information 

25 

39 

76 

103 

139 

166 

202 

225 

216 

259 

262 
182 

INNOVATION 

HOW THE FDA AND WAll STREET 

CRIPPLE MEDICAl ADVANCES 
183 

Introduction 

ou've heard of stand-up guys. Well, I'm a start-up guy. I've spent 

my entire twenty-five year career working for small company 

start-ups and "turnarounds" in the biopharmaccutical and 

medical technology communities. I've overseen the development 

and regulatory approval of three breakthrough medical products. 

I've also raised $160 million in the public markets. My passions are 

cancer and medical innovation. 

Innovation Breakdown-How the FDA & Wall Street Cripple Medical Advances highlights lessons that [have learned over my 25+ years, 

focusing particularly on the incredible and unprecedented behavior 

by the U.S. Food and Drug Administration (FDA) as well as the utterly destructive iniluencc of Wall Street's fast money hedge funds 

on a promising little company. 'D1e victim of that treachery and destruction? MELA Sciences, a small medical device manufacturer that 

has spent 17 years endeavoring to mitigate the debilitating effects of 

melanoma, the most aggressive form of skin cancer known to man. 

Over 150,000 Americans arc diagnosed with melanoma every single 

year, and one American dies every single hour of the disease. That's 

a tragic statistic, and for two reasons. lhe first: it's always a tragedy 
184 

IHNO'IATIOH BREAKDOWN 

when anyone dies. 'l he second: no one should die of melanoma. Why? 

Because it's the only cancer you can see coming, and it can theref(xe 

be eradicated if it's caught in time. And that's what MelaFind, a revolutionary product made by MELA Sciences, can help us do. But only 

about a hundred and fifty of the machines are in use today, as opposed to the much greater number that ought to be. As a result, more 

people are dying from melanoma than should be. The real victims of 

the FDA and Wall Street, in other words, arc the patients. 

The book includes a collection of first-hand, personal, and tellall stories about the long and arduous journey MELA took to get 

Melal0ind to market and the innumerable moments along the way 

when it was nearly derailed. First, the FDA tried to destroy it. When 

they couldn't, Wall Street tried. Neither succeeded, but they left the 

company so wounded that it might not actually survive, alone, in 

the end. The stories are alternatingly tragic and humorous, fascinating and frustrating. But they all highlight the unnecessary challenges of bringing true medical innovation to the people who need 

it-the patients. Here's the bad news: the system is horribly broken 

and needs to be fixed. But here's the good news: I know how to fix it. 

Innovation Breakdown is much bigger than one product or one 

person. The story of MelaFind, in other words, is simply the prism 

through which I hope to advance some broader truths and reveal 

the pervasive dysfunctions of a system that is supposed to help advance the cause of our collective heath but is actually hindering it. 

I wrote this book for several reasons, the most important of 

which was to sound the alarm about an emergency situation that 

matters to everyone. And it is this: if a revolutionary device such 

as MelaFind has to endure what it did in getting to market, there's 

almost no hope for those things that are equally revolutionary but 

also a little more complicated-a list that includes pretty much everything under development. Why is that i Because MelaFind isn't 

some futuristic biotechnology technology that does something like 

analyzing your DNA in real-time in the hopes of telling you about 

your medical future. It doesn't require a visit to an operating room, 

nor, in fact, does it require that you endure even the slightest bit 

of pain. It simply takes a picture of a questionable mole and gives 
185 

INTRODUCTION 

your dermatologist greater certainty in deciding whether that mole 

should be removed or not. That's it. And that's what makes this story 

so flabbergasting-if something that is both non-invasive and potentially life-saving had so much difficulty ftrst getting through the 

FDA and then through the gauntlet that is small-company public 

market financing, what does that portend for other true scientiftc 

breakthroughs that have the potential to help tens of millions of 

Americans live happier, better, and longer lives' MelaFind is based 

on technology that's been deemed good enough to be used in the 

U.S. Star Wars missile defense program that protects us from enemies outside our borders. And yet a bunch of Washington bureaucrats and Wall Street shysters tried to stop us from using it to protect 

us from enemies inside our own bodies. 

I hope this book can educate the public about the innovation, 

regulatory approval, and marketing challenges that every medical 

technology company faces at one time or another. I hope that it 

will inspire people with its tales of persistence and leadership and 

also entertain with real-life drama and humor, otlen in the face of 

pending doom and certain failure. I hope it will encourage others 

who have experienced similar treatment at the hands of regulatory agencies and other parts of this broken system to speak out 

in support of its reform, for that is the only way it can be fixed. But 

most importantly, I hope it will inform the collective consciousness 

of both the importance and opportunity of breakthrough medical 

innovation as well as the alarming threats that it faces. The implications are nothing short of profound: a failure to better foster innovation in this country will have disastrous effects not only on our 

health but on our economy too. 

Part One lays out, quite clearly, the devastation caused by skin 

cancer, and makes clear the need for something that can better help 

us detect it when it is curable. It also describes how medical innovation occurs in small companies and details the challenges in moving 

those start-ups along a course that is anything but straightforward. 

lt addresses issues such as the psychology of inventors and founders 

versus investors, the challenges of attracting and retaining talent, 

and the vagaries of early phase product development. 
186 

INNOVATION BREAKDOWN 

Part 1\vo takes a deep dive into the unlawful actions and coverups by the U.S. fDA that had to be overcome in our effort to bring 

MelaFind to market. 1hat is, to obtain approval of a non-invasive 

product that saves lives. It is a brutal blow-by-blow account of a public 

slugfest that ((>rever damaged the company. While the right side won 

in the end, it was nevertheless a bitter-and important-enough fight 

that it ended up being chronicled by the country's major media-the 

Wall Street Journal, Bloomberg TV, and Fortune magazine. 

Part Three explains how the unnecessary and very public battle 

with the FDA left an indelible mark on the company, a taint that was 

exploited by nefarious Wall Street actors who then preyed on the 

company for their own benefit. It details how with a Scarlet Letter on 

its back and an albatross around its neck, Wall Street's short sellers 

and dark pool traders made it impossible for the company to advance 

the product along the normal, yet time consuming and expensive, 

course toward widespread use and adoption. That's a path that every 

medical innovation must take en route to becon1ing a n1edical staple, 

but it's also a path along which Wall Street's bad actors lie in ambush. 

Here's the silver lining, though: until this system is fixed, it does 

offer long-term investors extremely attractive opportunities to invest 

in oversold stocks like MELA. I was unoble to secure such investment 

as CEO of the company, but had I been on the other side of the table, 

I surely would have invested myself. The opportunities arc numerous. 

Port Four oflers a cure for the broken system that nearly ruined 

the company, and in doing so has arguably killed countless patients 

by delaying, if not ultimately preventing, widespread adoption of 

this product. Simply put, the FDA has stopped pursuing its mandate 

to promote the public's health. Instead, it has put up every roadblock imaginable to stop true breakthrough medical innovation. If 

we don't cure what ails the system, it's going to succeed in stopping it entirely. clhe book concludes with a prescription for change, 

a Medical Innovation Manifesto. 

I hope you enjoy reading it more than l did living it. 

JOSEPH GUU'O 

June, 2014 
187 

STATEMENT OF 

NANCY GOODMAN 

EXECUTIVE DIRECTOR 

KIDS V CANCER 

BEFORE THE 

COMMITTEE ON HOMELAND SECURITY 

AND 

GOVERNMENTAL AFFAIRS 

U.S. SENATE 

FEBRUARY 25, 2016 

Connecting Patients to New and 

Potential Life Saving Treatments 
188 

Thank you Chairman Johnson, Ranking Member Carper, and Members of the 

Committee for inviting me here today. I am honored to testify before you about 

how to connect patients to new and potential life saving treatments. 

I am the Executive Director of Kids v Cancer. But more importantly, I am the 

mother of Jacob, a very sweet, beautiful boy who died when he was 10 of a 

pediatric brain cancer. Despite the remarkable developments in cancer research, 

the drugs and protocols used to treat Jacob were 40 years old. The day after 

Jacob died, I launched Kids v Cancer to focus on changing the landscape of 

pediatric cancer research and to make it possible for children to get access to 

cutting edge new treatments. 

When Jacob was in end stage cancer, I contacted eight different companies, 

requesting access to their unapproved drugs for Jacob. Finding the right person 

to contact was very difficult. The companies did not have point of contacts on 

their webpages, SEC filings or other public outlets. For some companies, I 

contacted the CEO, others the CMO, other the head of business development. For 

one company, it was my cousin's friend. It was all very ad hoc. The process was 

confusing and took me away from my son. Of the eight companies, six never got 

back to me. Two formally considered my request and declined. 

The purpose of the Right To Try laws is to help patients get access to drugs they 

would not otherwise get access to. That is a serious problem, and that is a goal I 

share, but I think we need to take a broader approach to this problem and that 

has been the focus of Kids v Cancer. 

Kids v Cancer's first step was to incentivize companies to develop drugs 

specifically for pediatric cancers and other pediatric rare diseases. In 2012, 

Congress passed the Creating Hope Act as part of PDUFA. That has created 

nearly $800 million in market incentives- at no cost to the taxpayer- for 

companies that get a new drug for pediatric cancer approved by the FDA. The 

Creating Hope Act is up for renewal as part of the 21'1 Century Cures bill passed 

by the House. I urge the Senate to renew it as well. 

Our second step was to make news drugs being developed for adult cancers 

available for kids as well. In 2003, Congress passed Pediatric Research Equity 

Act (PREA), which requires companies developing drugs for adults to conduct 

pediatric trials on such drugs where it could benefit children. The problem is that 

PREA has not kept up with the science. PREA only requires clinical trials if the 

children have the same "indication"· that is, if children have the same type of 

cancer. But now we know that even though children don't get breast cancer or 
189 

lung cancer, the mechanism of action in these cancers might also be evident in 

pediatric cancers such as neuroblastoma or medulloblastoma, the type of brain 

cancer Jacob suffered from. 

We have a proposed the Kids Innovative Drugs Initiative, a modest change to 

PREA that would update it to take into account these new scientific developments 

and ensure that drugs being developed for adults that could have relevance to 

pediatric cancers are tested on children as well. I urge Congress to pass the KIDS 

initiative as soon as possible, either as part of the 21st Century Cures bill or as 

part of PDUFA. 

And that brings me back to Right to Try laws. Yes, when it comes to seeking 

compassionate use access to unapproved drugs, the paperwork is onerous and the 

process time-consuming. In response, Kids v Cancer is launching a 

Compassionate Use Navigator. We are working to better inform physicians on how 

to apply for compassionate use applications for their pediatric cancer patients 

with drug companies, the FDA and their hospitals. We hope to provide point of 

contacts for drug companies, we will post the new FDA expanded access form, 

and we will work with the institutional review boards of the hospitals where the 

patients will be treated. We will offer to counsel physicians personally on specific 

applications. In addition, we will collect information about the efforts and 

outcomes of pediatric cancer compassionate use applications. 

The Compassionate Use Navigator is not the whole solution to the challenge of 

access to new treatments. However, it will give parents of dying children more 

time with their kids. It will lessen the burden of their physicians as they apply for 

compassionate use applications. We hope it will encourage more physicians of 

kids with cancer to apply for compassionate use. And, we hope this program will 

eventually lead to more children gaining access to compassionate use drugs. 

In addition, Kids v Cancer supports the Andrea Sloan CURE Act to have drug 

companies make available to the public their policies on requests for 

compassionate use access, including the minimum criteria for approving requests 

and the time needed to make a decision. I urge Congress to pass the Andrea 

Sloan CURE Act as part of the 21'1 Century Cures bill. 
190 

But from my personal experience and from working with dozens of other families, 

my sense is that the fundamental problem is not the FDA, but the incentives 

faced by the companies. Even though the FDA approves virtually all 

compassionate use applications it receives, and even though it has indicated that 

an adverse reaction to a drug provided for compassionate use will not adversely 

affect a company's application for that drug's approval, companies remain risk 

averse and would rather not provide such drugs. 

But even if one could change that, the results would be one-off anecdotes. We 

cannot afford to take an ad hoc approach to addressing pediatric cancer, the 

number one disease killer of children in America. We need to address the lack of 

access seriously ill children have to novel, unapproved drugs not only by one-off 

compassionate use applications, but even in clinical trials. That's why initiatives 

such as the Creating Hope Act and the KIDS Initiative are so important. 

Any bill that makes it easier for children to get access to drugs they need to 

survive and live happier, healthier lives is, of course, welcomed, but we need to do 

more than address anecdotes. We need to change the landscape of pediatric 

cancer research. We need to ensure that children with cancer and other life 

threatening illnesses, like my son, Jacob, have access to new and potentially life 

saving treatments. 

Thank you ve~much. 
191 

Meet Jordan Mclinn ... my 6 year old son from Indianapolis, IN. 

Diagnosed with Duchenne Muscular Dystrophy at age 3. Life expectancy 20ish. Unacceptable. 

Treatments existthat can slow the 

progression of this muscle wasting disease! 

Please help Jordan and other boys like him 

access safe treatments that can add time and 

quality to their lives. He is already starting to 

decline physically. He is in a race with the 

clock for his life. 

Please consider sharing your voice at the 

upcoming advisory committee meeting for 

eteplirsen to remind the FDA to use the tools 

you gave them in 2012 with the passage of 

FDASIA. The FDA has the power to say YES for 

the first time in history to a drug that slows 

the progression of Duchenne Muscular 

Dystrophy. It's a drug that is safe ... and 

working! After four years, 10 out of the 12 

boys receiving eteplirsen were still walking. This is unprecedented. Only one of the 13 boys in the 

external control group was still walking after four years. 

Jordan does not have time to wait for the standard approval process for these treatments but you gave 

the FDA the tools and support they need to grant accelerated approval ••. just like they've done with 

HIV/AIDS, several types of cancers and other diseases. We need your help encouraging them to use 

these tools more often with rare diseases like Duchenne so that boys like Jordan can live longer, walk 

longer, feed themselves longer and hug their mommies longer. 

Sincerely, 

~ Cu~.- -v;.___ ~; Laura Mclinn, Jordan's Mommy 

(317) 753-1661 

Laura M clinn@ya hoo .com 

www.TeamJordan.org 

• A decision on the accelerated approval of eteplirsen is expected to be made by the end of May. We are 

currently waiting for the new advisory committee date to be posted. It was postponed in January due to 

the blizzard. They will post the new date on the federal registry, hopefully any day now. 
192 

Jordan Joseph Nelson Mclinn, Age 5 

Date of Birth 5/15/09 

6131 S. Meridian St. Indianapolis, IN 46217 

Mommy's contact info: tl]_sJC:J~II?flg:,y~[?_@Yl!QQ_Q c~m (317) 753-1661 

Objective: To obtain a job at the fire 

station helping the firefighters. 

Qualifications: I am strong. I love 

God. I love helping people. I am super 

smart. 

Challenges: I have Duchenne 

Muscular Dystrophy. Science says 

within 3 to 7 years I will be in a 

wheelchair and within 15 years I will 

most likely be living in heaven 

because all my muscles will be 

deteriorated. We don't really believe 

that though. 

Skills: Taking Care of Dogs, Cleaning, Building Things, Playing 

with Cars & Trucks, Dancing, Cooking, Making People Smile 

Jordan says he wants to be a firefighter when he grows up. He was given a fatal 

diagnosis of DMD last year. It would be awesome if there is anything he can do maybe 

once a week for a short lime to help out at the fire station. We are pretty flexible with 

days/times. He is an awesome little boy, happy and full of life! Please let me know if I 

can bring him in for an, "interview". Thank you for your consideration. 

Laura McLinn @ 
193 

Cele&rat'tnq ltOYearsU 

of Hope 

February 19,2016 

Sen, Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

MACC 

FUND 

Hope for Kids 

On behalf of the children and their families, thank you for your continued interest in the fight against childhood cancer. You have 

shown a great personal interest through your willingness to meet in Milwaukee with some of our great doctors in the MACC Fund 

Center at Children's Hospital of Wisconsin as well as meeting with other childhood cancer advocates in Washington, DC. Your 

willingness to Chair this Hearing to better understand the issues will be most hopeful as well. 

Eddie Doucette and I started the MACC Fund 40 years ago to help provide funding in large part at the time to help Eddie's son, 

Brett, who was a toddler battling leukemia. l saw firsthand the impact of cancer in a child and the effect it has on the families. 

When we started the MACC Fund in 1976, the overaU cure rate for childhood cancer was 20%. Four decades later, that overall 

cure rate has risen to 800/o. The MACC Fund support totaling over $55,000,000 has played an important role in this along with 

federal support. Even children in the 80% category car~ have "late effect" issues and can relapse requiring more research. Cancer 

is still the leading disease~related cause of death in children with cancer, just !ike it was 40 years ago. 

The look in the eyes of a parent dealing with cancer in 2016 is the same as it was in 1976. lt is a look of fear. The most common 

theme from the hundreds of parents I have met over the years is that of Hope. They view the MACC Fund's mission of"Hope 

Through Research" and increased cure rates as tangible signs. That fear is punctuated by the financial to!J on a family which is 

overwhelming ns concerns over "making ends meet" is a constant concern. 

The MACC Fund is proud to be part of the solution in the proverbial private I pub tic partnership of support. The $55 million 

which the MACC Fund has contributed in Wisconsin to provide cutting edge research lit the Medical College of Wisconsin in the 

MACC Fund Rexearch Center, at Children's Hospital of Wisconsin in the MACC Fund Center and at the University of 

Wisconsin's Carbone Cancer Center in the MACC Fund Childhood Cancer Research Wing has led to exciting results which 

impacts the treatment of children throughout the state, the nation and the world, The evolution of gene therapy holds great 

promise. All of us hope for a cure in our lifetimes. If not us, our granddaughters will celebrate that day. 

While an ultimate cure is our goal, steps taken along the way by Congress to help eliminate red tape, provide incentives for 

innovation, remove the existing barriers which stand in the way while stream lining the processes for families which are already 

facing far too much would be most helpfuL We just had our annual meeting including a presentation from Dr. David Margolis, 

whom you met and who is one of the nation's brightest stars in cancer. He told a story of a drug which could have helped one of 

his patients, but regulations did not allow it to be used for a child- even though it could have saved the child's life. The sadness in 

his voice told it all. Thus, your efforts in strcllmlining "Right to Try" initiatives are most welcome. As a father and grandfather 

!ike me, I know you and your Msociates will do all you can to help the children. 

Thank you once again for your ongoing interest, support and leadership. 

Sincerely, 

:-:<:n !om ('urper 
194 

February 26, 2016 

U.S. Senator Ron Johnson 

Chairman 

REBECCA KLEEFISCH 

Lieutenant Governor 

STATE OF WISCONSIN 

Committee on Homeland Security and Govermnental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman Johnson: 

I understand that you are holding a hearing this week on opporhmities to reform the 

Food & Drug Administration's processes in order to provide greater flexibility for 

terminal patients to explore additional treatment options. As you consider these policy 

issues, permit me to share my family's story as one example of the impact of these 

legislative choices. 

Long before my own cancer diagnosis, there was my father's. At age 52, 36 years into 

his romance with my mom, the strongest man I knew was given monU1s tci live with 

pancreatic cancer. Everyone knows that's a killer. That's what I found out when I 

looked it up. I was a journalist at the time, and, accustomed to digging for answers, I 

sought advice from a more senior reporter ... who also happened to have cancer. 

Duane Gay was a Milwaukee TV legend whose status was elevated even further when 

he welcomed viewers into his very personal, ferocious battle with a rare soft-tissue 

cancer. When I reached Duane, he was trying another experimental drug. His will to 

live was enormous. He was a newlywed, building his dream house with his new bride, 

and hopeful to return to a career he was born to do. I asked for advice for Dad. Duane 

had seen all the cancers; they all pass you in the oncology ward or the radiation floor. 

He knew my dad had a bad one and so he fast-forwarded. 

"Just try anything,'' he advised, referring to the experimental drugs he was known for 

taking. "Anything to keep you alive until ilie next best U1ing comes along. And then 

iliat will keep you alive until the next best iliing." Duane tried study drug after study 

drug. When one didn't constitute a total fix, but gave him a few more weeks of life, he 

tried ilie next trial drug he could get. Duane didn't need to tell me U1at one day, he 

hoped "the next best thing" was the drug that would finally cure his cancer. He didn't 

need to tell me. I understood. 

19 East, State Capitol, Madison, W153702 (608) 266-3516 Fax: (608) 267-3571 

ltgov@wisconsin.gov www.ltgov.wi.gov 
195 

Page 12 

My Dad didn't have time to get into clinical trials, though. Most he was excluded from. 

I called doctors in the U.K., Canada, and across America to discuss their research that I 

had read in medical journals online. Dad didn't qualify to use any one of their drugs or 

procedures. Our doctors told us that my dad would die from his pancreatic cancer. I 

was convinced that with enough work I could find" anything to keep him alive until the 

next best thing comes along. And then that would keep him alive until the next best 

thing." But my dad never had access to the next best things. I would read about 

hopeful advances, only to have my hope dashed when no human trial was available, no 

FDA approval yet on the horizon ... at least not on Dad's time-frame. The horizon came 

quickly for Dad. It was only about four months and I was never able to find the same 

experimental drugs that kept Duane going. I wonder if Dad had had the right to try 

experimental treatments one of them would have been the next best thing. I will never 

know, but some patient might. 

A patient like the lady in the red knit cap at Serb Hall I met last Friday. She came up to 

me after I had given a speech and she told me that, just like me, she had been diagnosed 

with colon cancer. But unlike me, she had not recovered. Like my dad, she was Stage 4. 

I told her that I hoped her oncologist would one day be a stranger to her. I promised I 

would pray for her. And I told her to "just try anything. Anything to keep you alive 

until the next best thing comes along. And then that will keep you alive until the next 

best thing." I told her to keep hoping, because the next best thing might be a cure for 

her. Cancers seem to be deeply personal. A drug that kills cancer in one patient may be 

like a sugar pill in another. But on the hope that just one patient, left alone after every 

effort by conventional medical logic, might be that miracle, shouldn't those with little 

hope left have a right to try? 

Sincerely yours, 

Rebecca Kleefisch 

Lieutenant Governor 

State of Wisconsin 
196 

February 24,2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

My name is Stephen Finger. I am 39 years old and am an economics professor at the University of 

South Carolina. I grew up across the river from the Capital in Arlington, Virginia. I went to Yorktown 

High School and then to Princeton. Three years ago I was diagnosed with ALS. Between my son 

James's first birthday and his sister Mary Adair's third, I was told, what I thought was a minor issue 

with my hands, was a disease that would rob me of my ability to play catch, to play tag, to walk, to 

speak, to eat, to breath. 

My family's lives where forever changed and if one thing was clear, it was that time was of the 

essence. And just as we recognized the need to live urgently; to hug today, to laugh today, to live 

today, to love today. We also recognized the need to act today. I applaud the Committee for looking at 

this issue and I urge you to direct the FDA to utilize the tools at their disposal to facilitate the search 

for a cure for ALS and other serious diseases with limited therapeutic options. While in an ideal world 

it would be nice to completely rewrite the regulations related to drug development, the first step is to 

simply make sure current regulations are enforced and utilized in the ways that they were intended. 

The 2012 Food and Drug Administration Safety and Innovation Act, with near unanimous support in 

both the House and Senate, reinforced the "Agency's longstanding commitment to regulatory 

flexibility regarding the evidence required to support product approval for the treatment of serious or 

life-threatening diseases with limited therapeutic options". Every now and then, you hear about a 

disease like Ebola that captures the public's attention that leads to aggressive action by the FDA. Even 

though ALS may not have the same PR campaign behind it, to the patient who is diagnosed every 90 

minutes, to the families who lose a loved one to the disease every 90 minutes, ALS is no less a 

nightmare. We ask that the FDA uses the flexibility, efficiency, and urgency required to fight this 

disease, and mandated by law. 

Accelerated Approval is not a new program. It has been around for over 20 years, specifically designed 

for situations like this. Congress has provided the FDA with the ability to act with the urgency this 

situation merits. Because ALS is a complex disease and progressions vary, meeting traditional 

standards of efficacy will require additional large and lengthy trials. Well we don't have time for that 

and Accelerated Approval was specially designed to address this. That is the directive Congress has 

given. I have spoken with decision-makers with the FDA and they insist that they are open to 

examining applications for accelerated approval. However when I have talked with researchers and 

sponsors, they stressed they do not 122 anything that jeopardizes their relationship with the FDA. 

Therefore it is vital that the FDA publicly directs sponsors to utilize these types of programs in the 

many disease spaces where they are not cuiTently used. 

Now sure after Phase I and Phase II trials there are still risks, but there will still be risks after Phase III 

and more importantly, we all know what the risk of inaction is. Accelerated Approval does not mean 
197 

we enter the wild, wild west, Postmarketing surveillance data must still be collected and approval 

could still be revoked if confirmatory trials do not go well. Some patients may be angry if approval is 

revoked for a treatment that they believe is being beneficial. However, isn't that aPR issue that we are 

willing to bear in order to give dying patients access to potentially effective drugs? Given safety data, 

given evidence of efficacy, given the prognosis of the disease, given the urgency of the situation, isn't 

that a risk we are willing to take? Isn't that a risk the FDA is supposed to take? 

Since 1962, by law, the FDA has required "Substantial evidence" of effectiveness. The required 

statistical significance level for any trial should minimize the impacts of Type I and Type II errors. To 

my knowledge there is nothing that states that p<0.05 for a two-tailed test is substantial, but 0.10 is not 

or p=0.05 for a one tailed test is not. 

No one wants to risk switching to a new mouse trap if the current one is working. However, if the 

cunent one isn't working, or in the case of ALS you currently do not have one, you are more willing to 

take a chance on a better mousetrap. In a disease such as ALS, with few clinically significant treatment 

options and a stark prognosis, the cost of approving an ineffective or dangerous treatment (I in 40 

under their cunent statistical standard), must be weighed against the cost of delaying or rejecting an 

effective treatment given the alternative for patients. Delaying approval for an effective treatment 

means that more of my friends will die, it decreases the odds that I will see my kids grow up. 

At a minimum, p=0.05 for a one tailed test is more appropriate in this setting. The purpose of a trial is 

to test if a treatment is effective. Therefore, the null hypothesis should be that a treatment is not 

effective. As with accelerated approval, as long as the FDA insists on adequate postmarketing 

surveillance and data collection, the impact of giving conditional approval to a treatment that is 

ultimately proven to be ineffective can be minimized, while we expedite the availability of effective 

treatments to this population. 

I believe in many ways the FDA is at a crossroads. New technology, more personalized medicine, and 

better data analytics is changing the way that trials will be conducted in the future. In addition, patients 

now have better ways to coordinate and make their voices heard. They will not die quietly while a risk· 

averse system speaks eloquently about a one-size-fits-all status quo. I will not do that. I will fight for 

the system to work for me so that l can see my son's first day of kindcrga1ten, so I can see my daughter 

learned to ride a bike. Congress has done its part to give the FDA the tools to move into the 21" 

century and act more effectively, efficiently, and urgently to help sponsors find treatments to deadly 

diseases. It is now up to the FDA to choose to use these tools or to force more radical steps to be taken. 

I thank the Committee for working on this issue and I thank the FDA for doing everything possible to 

speed drug development for serious diseases with no cunent treatment options. 

Sincerely, 

Stephen R. Finger, PhD 

1319 Greenhill Rd. 

Columbia, SC 29206 

803-361-0644 
198 

February 20, 2016 

Senator Ron Johnson 

Chairman Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Regarding the February 25 Hearing- Connecting Patients to New and Potential Life Saving Treatments 

Dear Chairman Johnson, 

Three years ago to the day of this hearing, the FDA conducted an ali-day hearing on ALS. Dozens of 

people with ALS and caregivers made a difficult trip to Silver Spring to testify. Dozens of scientists and 

organizational representatives testified, too. It was a day when FDA officials sat face-to-face with dying 

people who were begging for the right to take some risks. It was a day when caregivers gave the FDA 

some concrete suggestions for changing the drug approval process to save their loved ones. it was a day 

when a mother of a young man with ALS asked that this not turn out to be a dog-and-pony show. Three 

years later, it is clear that it was nothing more than a dog-and-pony show. 

Three years. 20,000 American funerals later. A half million global funerals later. We all deserved more 

than a dog-and-pony show. 

I realize that the FDA has a huge responsibility to keep Americans safe. I appreciate that. They would 

rightly feel blood on their hands if something were approved that did more harm than good. Why don't 

they feel the blood on their hands today when people die from ALS, protected to death from 

experimental drugs? Why don't they feel the blood on their hands today when people with ALS die from 

the FDA-approved morphine that makes them more "comfortable" in death? 

A basketball game is played differently in the last 60 seconds, especially when you're behind. The last 

two minutes of a football game can be a magnificent display of adapting to the situation. Yet our gameplanners for drug access and approval have one playbook. Today the drug approval process for a simple 

therapy for a relatively healthy child is substantially the same as for a possible drug for that child's 

parent dying from ALS. No Hail-Marys are allowed for that child's Mom or Dad. That's just wrong. 

I personally think that Right-to-Try laws are not the answer. We need a strong FDA at the center of drug 

development. We shouldn't be building networks of drug access that only work for people of 

substantial means. Yet those Right-to-Try laws have brought an important conversation to this hearing, 

and I am grateful forthat. 

The legislative Branch has provided the FDA with a path of Accelerated Approval that is designed to let 

them change the game plan for terminal, unmet-need diseases. Why doesn't the FDA use it for ALS? Is 

it liability? Is it concern over payers (which I don't believe is the responsibility of the FDA)? What is the 

problem? 

And please don't try to tell us that Expanded Access Programs are the answer. They simply aren't viable 

when the entire market for a new drug is the unmet-need disease and the science is dreadfully 

expensive. They don't work for ALS. We need to encourage drug developers, not discourage them. 
199 

We learned at that FDA hearing three years ago that drug developers are frustrated because they don't 

get to collaborate with the FDA. They submit. The submission is accepted or rejected. If it's the latter, 

they have to start over. Are drug developers afraid to propose new ideas for fear they will be rejected? 

I'm a Boomer. I'm old enough to remember when we all had access to drugs that had just been tested 

for safety but not for efficacy. As an adult today blessed with good health, I appreciate the FDA changes 

of the 1960s that require efficacy testing of the drugs my doctor prescribes. But as the daughter of a 

woman lost to ALS, I also know that she should have been given a chance to try something-- something 

that may or may not have helped her. Something she could have accepted with eyes wide open about 

risk. Something that could have advanced the science more quickly for another mother. 

Last year Gregg Doyel, a talented sports journalist for the Indianapolis Star, wrote a column about his 

friend, Maureen, who was dying from ALS. She was a beautiful human being. She was a mother and 

wife. She wanted access to try something. She wanted a chance at a Hail Mary. Gregg's article ended 

with some words that I hope stick with everyone in this hearing room. Actually, I hope they sting, too. 

-"For god's sake, you coldhearted bureaucrats, they're dying." 

Sincerely, 

Mary Catherine Collet 

4475 Clover Lake Drive 

Indianapolis, Indiana 46228-3044 

317-293-5013 

mcollet@comcast.net 

cc: Senator Thomas Carper 

cc: Senator Dan Coats 

cc: Senator Joe Donnelly 

cc: Senator Lisa Murkowski 
200 

The Honorable Ron johnson 

Chairman 

February 24, 2016 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Mr. Chairman, 

In light of the hearing you are holding tomorrow entitled Connecting Patients to New 

and Potential Life Saving Treatments, I want to urge you to consider the importance 

of extending the right-to-try principal through accelerated drug approvals and 

expanded access to experimental drug trials. Patients diagnosed with terminal 

illnesses without known cures deserve every opportunity to try and fight for their 

lives. Ensuring expanded drug access and faster drug approval times by the Food 

and Drug Administration is critical for improving these patients' chances of survival 

and quality of life as they battle devastating diseases. Furthermore, the desire of 

these patients to control their own destinies is also in the public interest, as 

experimental treatments provide important data and evidence that help advance 

the body of knowledge to the benefit of all Americans. 

I know firsthand the devastation of incurable disease as my mother was diagnosed 

with ALS last year and died September 12, 2015. Of the many terrible memories of 

this experience, the one that most impressed itself on me was her unwavering 

desire to fight her disease as best she could, and to control the outcome to the best 

of her ability. I wish fervently that she had had more options to try in her fight. 

While mine is only one example, I know that there are many other Americans who 

wish, along with their families, to have the right to try potential drug treatments as 

they battle terrible illnesses. I urge you to take the lead in changing our outdated 

drug approval process in order to provide this right to those who wish to take 

control of their own fate when faced with a terminal diagnosis. 

Sincerely, 

Sabrina Abu-Hamdeh 

CC: Senator Thomas Carper, Ranking Member121 
201 

The Honorable Ron Johnson 

Chairman 

February 24, 2016 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Mr. Chairman, 

In light of the hearing you are holding tomorrow entitled Connecting Patients to New 

and Potential Life Saving Treatments, I want to urge you to consider the importance 

of extending the right-to-try principal through accelerated drug approvals and 

expanded access to experimental drug trials. Patients diagnosed with terminal 

illnesses without known cures deserve every opportunity to try and fight for their 

lives. Ensuring expanded drug access and faster drug approval times by the Food 

and Drug Administration is critical for improving these patients' chances of survival 

and quality of life as they battle devastating diseases. Furthermore, the desire of 

these patients to control their own destinies is also in the public interest, as 

experimental treatments provide important data and evidence that help advance 

the body of knowledge to the benefit of all Americans. 

I know firsthand the devastation of incurable disease as my mother was diagnosed 

with ALS last year and died September 12, 2015. Of the many terrible memories of 

this experience, the one that most impressed itself on me was her unwavering 

desire to fight her disease as best she could, and to control the outcome to the best 

of her ability. I wish fervently that she had had more options to try in her fight. 

While mine is only one example, I know that there are many other Americans who 

wish, along with their families, to have the right to try potential drug treatments as 

they battle terrible illnesses. I urge you to take the lead in changing our outdated 

drug approval process in order to provide this right to those who wish to take 

control of their own fate when faced with a terminal diagnosis. 

Sincerely, 

Sabrina Abu-Hamdeh 

CC: Senator Thomas Carper, Ranking Member111 
202 

February 23, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Christopher Engstrom 

1295 Herringbrook Rd. 

Eastham, MA 02642 

Dear Chairman, 

I am only 44 years young. I now live with my parents who are 72 and 78. I have had ALS for four 

years; I cannot walk, talk, move my arms nor my hands. I cannot swallow and have to eat 

through a feeding tube. My breathing is shallow and I may soon need to have a tracheostomy 

and a rely on a vent to survive. 

Four years ago I was very healthy and athletic. I have been a long distance runner since high 

school and a competitive swimmer since age seven. For my entire life, I have defined myself as 

an artist and being passionate about immersing myself in nature. As a teacher, I taught my 

students that the natural world is not separate from us; it sparks curiosity, creativity, holds 

insights and is key to our survival. Nature is everything to me. In sum, I LOVE LIFE and I don't 

want to give it up' 

I never thought this would or could happen to me. I didn't even know what ALS was. Now I 

cannot draw or paint and my running, hiking, swimming, surfing and skiing has been replaced 

with wheelchair accessible paths. I should not complain that I may have less than one year of 

life left to live because I have had opportunities and experiences that the majority of people 

have not. I grew up in an upper middle class neighborhood; I have always had running water, 

clean clothes, an abundance of nourishing food, excellent education, a home and a loving 

family. 

So why should anyone care about me? I ask myself that daily. And my answer is that everybody 

is equal and we all have the right to live. It does not matter what race, gender, ethnicity, religion, 

social status or income level we are; anyone could find themselves in my shoes-with a 

terminal illness with no known cure. possibly one year to live, no hope to prolong life and no 

options. Shouldn't we ALL have the right to try promising medicine that is not yet approved by 

the FDA if we are faced with death? Wouldn't you want this for your family? Wouldn't you want 

the FDA to do everything in its power to fast track a promising new drug .or treatment? 

It is the death of hope that destroys the soul; the body follows. I am nearly out of hope. How 

much more does my family and I have to endure? Because my disease has advanced so 

quickly, I never qualified for trials. Now my only option for hope is having a tracheostomy and be 

on a vent. I would need around the clock care which medicare does not cover. Therefore, I have 

to choose between my family's home, their freedom, the quality of their future lives and my 

future breathing through a vent and being completely dependent. 

Why don't I have more options? Me and thousands of others with terminal illnesses have the 

RIGHT TO TRY medicine that could help! FDA and Chairman, respectfully HEAR MY CALL!! 

Sincerely, 

Christopher Engstrom 
203 

Senator Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington D.C. 

February 23, 2016 

Dear Chairman Johnson, 

I'm writing to plead your help in expediting the process for trials/treatments for those 

who are terminally ilL January 11th, 2015 my otherwise extremely healthy, active 

husband, father, son, brother, uncle and friend was diagnosed with ALS, which as you 

know is a death sentence. We have three amazing children who will be left broken 

hearted without their father, and we are willing to try anything that offers HOPE and 

prolonged life. Mike would love to watch each of our kids make it through high school, 

and at this time, without the opportunity to pursue investigational medicines, this dream 

will most likely not be a reality. We are urgently pleading for you to please speed along 

the trials/treatments and open them up to whoever is willing to take the risk and try. 

There are many promising drugs/treatment on the horizon, but people fighting terminal 

diseases need them NOW! People with terminal diseases don't have time to 

lose. They don't have the luxury to wait five to ten years, while the FDA takes an 

inordinate amount of time to determine the "safety" and "effectiveness" of these 

trials. Simply put these patients have everything to lose if not granted the "Right to 

Try". 

There is a 100% chance that people with ALS and other terminal illnesses will die; there 

is no cure for this disease or many others. But if there is investigational 

drugs/procedures that many have some chance in helping people both recover their 

quality and quantity of life, they should be allowed to try it, at their own discretion and of 

their own free will. This is what Right to Try Laws allows for and should be on the 

forefront of reaching out to medical companies and allowing them to practice. 

For example, given the strong performance and good safety profile of neural stem 

therapies, virtually every person with ALS would want to participate in these procedures 

if they were afforded the opportunity. Why should people with ALS not be able to 

participate in this therapy as it has already been approved for muscle/tendon/joint 

repairs? The FDA needs to not stand in the way of promising medicines/therapies for 

those suffering with terminal diseases. The FDA, while under pressure, bent the rules 

in the 1980s and 1990s to allow drug access to patients with AIDS, then a fatal 

diagnosis. More recently, under the harsh light of international publicity, the FDA 

allowed for ZMapp, which had NEVER been tested on humans to be given to 

Westerners who contracted Ebola, thus saving their lives. 
204 

Please attend to this matter with a sense of urgency and willingness to fully consider 

and factor into the regulatory policy and decision making, the perspectives of all those 

suffering with a terminal disease that allows all the opportunity to access promising new 

medicines/treatments at the earliest possible point in the learning process. 

Thank you, 

Nicole Cimbura 

Highlands Ranch, CO 80129 
205 

February 21, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

As a parent that received a "terminal upon diagnosis" for my perfectly healthy nine-year old I struggle with 

the fact that, for far too many of us, there simply are no options. My daughter, Gabriella, was diagnosed with 

Diffuse Intrinsic Pontine Glioma, DIPG, a terminal brain cancer, in November 2012. This is the same cancer 

that Neil Armstrong's daughter had 50+ years ago. No viable treatments have been developed in all of these 

years. The outcome for those diagnosed remains the same- DEATH within 9- 12 months. 

WHY is it that we can successfully send a man to the moon- and return him to earth- but we cannot save his 

daughter or the thousands of children that have been diagnosed in these 50 years? WHY are we still giving 

children cancer drugs that were developed 30,40 and even 50+ years ago? Drugs that have known side 

affects such as organ failure, causing secondary cancers and death. Yet we have promising drugs that are 

currently being developed and available for clinical trials but our children cannot use them because they are 

for adult use only. Please explain this to me. 

When my daughter's cancer began to regrow post-radiation I called every hospital in the country that had 

some sort of protocol that held the possibility of extending and saving her life. To no avail. The general 

response from the doctors was that Gabriella was too young and that perhaps in 6 -12 months the trial 

would open for children. My daughter didn't have another six months. I BEGGED for my daughter's life and 

was basically told that her life wasn't important enough to make an exception. (Please note that every doctor 

that I spoke with was filled with anguish that the laws forbade them to fulfill their Hippocratic oath- to work 

in the best interest of their patient and to save every life that they could.) Do you know how many parents 

hear this exact same thing every day? Can you imagine having to beg for your child's life only to be told that 

even though there was a treatment that could potentially save their life it would never be available to them 

because the government wouldn't allow it? 

Why are there barriers that keep children from receiving potentially lifesaving therapies? Shouldn't every 

child have access to compassionate use? Why does the FDA have a god-like voice over who can receive 

treatment and who can't? Modernizing the FDA to allow the doctors and parents to make potentially life 

saving decisions for their terminally ill children could lead to a life saved, a new treatment or even a cure that 

would otherwise never been discovered. 

Thank you for your advocacy on behalf of our children. We need and appreciate your help and your voice to 

make the changes that will save lives. 

With high regard, 

Ellyn Miller 

Executive Director 

Smashing Walnuts Foundation 

~·(vfw ~rn?sJling~vaiGL~t?:9[9 
206 

February 21, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

As a parent that received a "terminal upon diagnosis" for my perfectly healthy nine-year old I struggle with 

the fact that, for far too many of us, there simply are no options. My daughter, Gabriella, was diagnosed with 

Diffuse Intrinsic Pontine Glioma, DIPG, a terminal brain cancer, in November 2012. This is the same cancer 

that Neil Armstrong's daughter had 50+ years ago. No viable treatments have been developed in all of these 

years. The outcome for those diagnosed remains the same- DEATH within 9-12 months. 

WHY is it that we can successfully send a man to the moon- and return him to earth- but we cannot save his 

daughter or the thousands of children that have been diagnosed in these 50 years? WHY are we still giving 

children cancer drugs that were developed 30, 40 and even 50+ years ago? Drugs that have known side 

affects such as organ failure, causing secondary cancers and death. Yet we have promising drugs that are 

currently being developed and available for clinical trials but our children cannot use them because they are 

for adult use only. Please explain this to me. 

When my daughter's cancer began to regrow post-radiation I called every hospital in the country that had 

some sort of protocol that held the possibility of extending and saving her life. To no avail. The general 

response from the doctors was that Gabriella was too young and that perhaps in 6- 12 months the trial 

would open for children. My daughter didn't have another six months. 1 BEGGED for my daughter's life and 

was basically told that her life wasn't important enough to make an exception. (Please note that every doctor 

that I spoke with was filled with anguish that the laws forbade them to fulfill their Hippocratic oath- to work 

in the best interest of their patient and to save every life that they could.) Do you know how many parents 

hear this exact same thing every day? Can you imagine having to beg for your child's life only to be told that 

even though there was a treatment that could potentially save their life it would never be available to thembecause the government wouldn't allow it? 

Why are there barriers that keep children from receiving potentially lifesaving therapies? Shouldn't every 

child have access to compassionate use? Why does the FDA have a god-like voice over who can receive 

treatment and who can't? Modernizing the FDA to allow the doctors and parents to make potentially life 

saving decisions for their terminally ill children could lead to a life saved, a new treatment or even a cure that 

would otherwise never been discovered. 

Thank you for your advocacy on behalf of our children. We need and appreciate your help and your voice to 

make the changes that will save lives. 

With high regard, 

Ellyn Miller 

Executive Director 

Smashing Walnuts Foundation 

YYYY:!i. _ ~!TL~-~bJng 'tv_~ ~J ~Jt~;,~· 9 f!J 
207 

smoshlng"'~>lnuh "",%\l>'lw 

Smashing Walnuts is a component fund of the 

Community Foundation for Loudoun and Northern 

Fauquier Counties, Tax ID: 54-1950727 

CC: Sen. Tom Carper 
208 

2/24/2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

My wife Trickett Wendler, passed March 18, 2015 after a 2 year battle with ALS. When she was first 

diagnosed, we scoured the country to find the best doctors, medicine, treatments, etc and were sadly 

disappointed to find the lack of measurable progress made for this horrific disease. In fact, the only 

"treatment" drug prescribed for my wife was the exact same drug that was prescribed to her father over 

20 years ago ... literally no progress. Without a known cause or cure, we were resigned to accept the 

unforgiving certainty of a terminal diagnosis. 

I will tell you that once we were out of options, our desire to transform the possibilities became the 

singular focus of our life. I have three small children with a hereditary gene that predisposes them to 

this intolerant disease. That is why it is infinitely important to provide patients with alternatives where 

none exist. The Right to Try provides something that doctors, drug manufacturers, legislators, etc, 

cannot provide: hope. Sadly, my wife did not have this option, but I write to you today to implore to 

you the importance of providing hope where none exists. I pray every day that progress is made to find 

a cure and that my children are not given the same drug that their mother and grandfather were given, 

but if none is made I pray that my children will have the Right to Try. 

Sincerely, 

Tim Wendler 

CC: Sen. Tom Carper 
209 

Patient Access to Investigational Therapies 

Many states across the country are cons1denng so,cal!ed "R1ght to Try" leg1slat1on to prov1de patients w1th access 

to Investigational therapies before they are approved by FDA. However, for over two decades, FDA has had 

processes in place to do JUSt that. Expanded access, which is sometimes ca!led ··-compassionate use," supplements 

the clinical trials process. FDA believes enrollment in clinical trials remains the best option for patJents wishing to 

gam access to investigational drugs-it assures adequate protection for patients and leads to the collection of data 

that could eventually result in FDA approval of the mvestigational therapy, which provides the broadest availability 

to pattents, Patients who are not eligible for a clinical trial because of where they live, their age, or some other 

disqualifying factor have the option to seek expanded access if they have serious or life-threatening conditions and 

no comparable or satisfactory alternative is available. 

FDA acts quickly in response to expanded access requests and allows almost all of them to proceed. In fact, FDA 

authorized more than 99 percent of individual patient expanded access requests recetved in Fiscal Years 2010-14. 

Emergency requests are often granted immediately over the phone. For non-emergencies, the Agency strives to 

respond promptly and, in general, does not take longer than 30 days. Moreover, FDA continues to improve its 

processes. In response to feedback from physicians that the expanded access form was cha!lengmg, in February 

2015, FDA announced the development of a new draft form for individual pattent expanded access that is 

estimated to take only about 45 minutes to complete. 

Expanded access to investigational treatments requires the act1ve involvement and cooperation of parties other 

than FDA, indudmg drug companies and healthcare provtders. FDA can encourage drug companies to offer 

expanded access to their investigational therapies, but companies may choose not to do so for various reasons, 

including lack of available drug or a desire to focus their attention on cornpleting the clinical tnals necessary to 

o.upport FDA approval 

Facts: 

FDA has a ffi.Dg;;tandmg and well-established process for md1v1dual patients to obtain access to 

mvestigational therapies-expanded access, which is sometimes called compassionate use 

FDA allows almost all expanded access requests to proceed: more than 99 percent of individual patient 

expanded access requests made from 2010-14 were granted. 

FDA responds to indtvidual patient expanded access requests qutckly; emergency requests are often 

granted immediatel.'i over the phone. For non-emergencies, the Agency strives to respond promptly and, 

in general, does not take longer than 30 dilys 

FDA IS improving expanded access to make it easier to apply; a new proposed form for individual patient 

expanded access requests ts estimated to take physicians only about 45 minutes to complete 

FDA IS an important part of the process and helps to ensure patients are adequately protected from unnecessary 

nsk. The independent scientific revtew provided by FDA is an essenttal component of patient protection, 

particularly because one is considering treatments for which safety and efficacy have not been demonstrated. 

Contact Us 

For more information, p!ease contact FDA's Off1ce of legislation at 301· 796·8900, or see FDA's website: 

http://www.fda.gov/~.~aJl_c;igdA~.?.-

Updated: November 2015 
210 

Page 1 of4 

Abigail Alliance for Better Acces,f to Developmental Drugs 

Board of Of rectors.· Doug Baxter: David's Father, Cancer Advocate, Gene Krueger: Abigoi!'s Step Father, Cancer Advocate, Anne Agnew: 

Strategy Consultant Entrepreneurial Ventures., Prince Agarwal: Deutsche Bank, Sjaak Vink: Board Member 

CuresWtthinReach, Cofounder myTomorrows, Ron Trowbridge: Supreme Court Chief Justice, Executive U.S. 

Information Agency, Cof!ege Vice President and Professor Ret. 

U.S. Senate Hearing 

Connecting Patients to New and Potential Life Saving Treatments 

Committee on Homeland Security and Government Affairs 

Dear Chairman and committee members, 

The American people are clearly speaking to the nation about the vital and doable need to bring 

change at the FDA to allow much earlier approval of promising investigational drugs. This is clearly 

seen in 24 states so far having past Right to Try legislation. 

Tens of thousands of lives could be saved and extended with changes at the FDA, and this could 

definitely be done without sacrificing good science. 

Below is some input from the Abigail Alliance. 

I strongly urge you to take progressive doable lifesaving action on this non-partisan issue! 

--:;;;?--,~ ..t:::::-:_)£:;:__ / 

Frank Burroughs 

President 

Abigail Alliance for Better Access to Developmental Drugs 

• Frank Burroughs is president of the Abigail Alliance for Better Access to Developmental Drugs, 

which since 2001 has been pushing the FDA and the U.S. Congress to bring about much needed 

change to save thousands of lives by getting promising investigational drugs for serious lifethreatening illness approved much earlier. His daughter, Abigail, was unable to get access to an 

investigational drug that was performing well in early clinical trials to treat head and neck cancer. The 

drug was approved for general use to treat that type of cancer 4.5 years after Abigail's 2001 death. 

A few hours after Abigail died Burroughs decided he would keep working to expand early access to 

developmental drugs. "Why should I quit now?" he asked. "There are other people as precious as 

Abigail." 

• Some say the FDA's compassionate use methods work. In reality, they work badly. Currently only 

1,000 to 1,200 patients receive FDA approved lndividuaiiND access (compassionate use) annually 

because most physicians cannot spend the required 100 hours to complete the application. If and 

when the new FDA shortened form is implemented, that number could potentially quadruple to 4,000 

patients. Sadly this represents only a small percentage of patients who need access. Despite the 

proposed shortened FDA application, many FDA obstacles remain. 
211 

Page 2 of 4 

• The Abigail Alliance for Better Access to Developmental Drugs has 14 years' experience 

advocating for earlier access and earlier approval of promising investigational drugs. We have heard 

from thousands of patients with no further FDA approved options left in their battle to live. These 

patients do not want indiscriminate access to drugs. These patients and their physicians seek access 

to investigational drugs with high promise. It may be years before these promising drugs receive FDA 

approval. 

•This statement comes from our www.abigail-alliance.org homepage: 

"Every drug for cancer and other serious life-threatening illness the Abigail Alliance has pushed for 

earlier access to and earlier approval of over the past fourteen years is now approved by the FDA, 

unfortunately years after patients tried in vain to get access and therefore died. Not one drug we 

pushed for earlier access to and earlier approval of failed to make it through the clinical trial process." 

Thousands of lives could have been saved with earlier access and earlier approval. 

Patients fighting for their lives need the 'Right to Try' 

nee existed} 

Fierce. 

Top 10 best-selling cancer drugs of 2013 

May 29. 2014 Cnrly Hellnnd 

Note: Abigail Alliance haro push1:1d for earlier access and earlier approval of drugs for ~tedous 

life~thre;teninc illnesses otMer than c:Jncl!r dru::s t"'::.t are now approved by the FDA, 
212 

Page 3 of 4 

o As the FDA's Science and Technology Advisory Board confirmed in 2007, the FDA could get drugs 

approved much sooner if the FDA updated its scientific and statistical tools. The Board strongly 

recommended changes in clinical trial designs and options for a provisional approval mechanism for 

promising investigational drugs. That report was written nine years ago. The FDA has not yet adopted 

these recommendations. 

• There have been times when investigational drugs have demonstrated significant efficacy early in 

the clinical trial process, even as soon as Phase 1 and Phase 2 trials. One example from 1999 was a 

Phase 1 trial for the cancer drug Gleevec for CML leukemia that had 30 of 31 patients in the trial go 

into remission. Although approved faster than most drugs, there were many people who died waiting 

for Gleevec's approval. Today, there are similarly promising drugs for Duchene Muscular Dystrophy 

and ALS. They too may require years for approval. 

o There are rare times when the Abigail Alliance and others are able to apply pressure to help a few 

patients fighting for their lives. Below is an example of one of these successes. Access to the 

promising investigational drug Josh needed saved his life' Unfortunately only 41 other patients could 

get the Drug, while others had to wait in vain. 

After much effort Jo~h Hardv's (fredericksburg, VA) 

7 year-old lif€ was saved. because he was able to get a 

promising developmental drug. More chi!d~en and adult 

could be saved 1f we can continue to bring abcut more 

much needed chong?. at the FD,~. Josh just turned 9i 

This begs the question, what about the children and adults that died, 

because they could not get this lifesaving drug! 

Myths 

o Right to Try would result in a 'Dallas Buyers Club' environment. 

Definitely not true. Efforts to get earlier access and earlier approval of promising lifesaving drugs 

would be limited to drugs that are in FDA approved clinical trials and are showing significant efficacy. 

What is very interesting is that the thousands of patients the Abigail Alliance for Better Access to 

Developmental Drugs has heard from over the past fourteen years are trying to get drugs that are 

showing significant promise in early clinical trials and are designed for their disease. By the way 

these are people who have tried and have been unable to get into clinical trials. Only 3% of people 

who try to get into clinical trials for lifesaving drugs are able to do so. 
213 

Page 4 of 4 

• Earlier access to drugs would hurt clinical trial enrollment. 

Not true. Because of the long efforts of the Abigail Alliance lor Better Access to Developmental Drugs 

the FDA is now designing more and more trials lor serious life-threatening illnesses that do not have 

placebo arms. A patient in the clinical trial would be getting the drug along with those outside the 

clinical trial. 

II there is a placebo arm, access to drugs outside clinical trials could be limited to those who have 

tried and could not get into a trial. 

As pointed out in bullet lour on page 1, in 2007 the FDA's own Science and Technology Advisory 

Board recommended earlier access to promising investigational drugs lor patients who could not get 

into clinical trials. Additionally it should be noted that the board's report was very critical of the FDA 

not using more modern tools and techniques in their clinical trial designs and drug review process, 

which includes trials designed without placeboes. 

• What if a company cannot provide enough drugs to meet the need of patients? 

This can happen, but the few programs (expanded access) that have been run in the past, use a 

lottery system. One well know third party that has run these programs in the patient advocacy group 

NORD (National Organization for Rare Disorders). 
214 

[e~~~ Americans For 

-..Safe Access 

Dear Chairman Johnson and Ranking Member Carper, 

February 24, 2016 

Thank you for addressing the issue of barriers to new treatments by holding Thursday's hearing on 

Connecting Patients to New and Potential Life Saving Treatments. As the nation's largest memberbased organization working exclusively on advancing safe and legal access to medical cannabis 

for patients and researchers, we are all too familiar with research and access. 

While agencies within the federal government, such as the Food and Drug Administration, the 

Drug Enforcement Agency, and others, have been slow to address cannabinoid-based therapies, 

40 states have sought to protect patients who use medical cannabis products under the 

supervision of their physician. Unfortunately, these patients must break federal law in order to find 

relief and well ness through medical cannabis products. Whether it be in the raw, dried flower form, 

or extracts for high concentration of certain cannabinoids (including CBD, THC, THCA, and 

others), federal law prevents patients from accessing these therapies and prevents researchers 

from learning more about how these products can best treat patients. 

Attached, you will find stories of American families who use varying cannabinoid profiles to treat 

their conditions. Americans for Safe Access (ASA) urges the Chairman and the Committee to take 

a look at the complete range of cannabinoid profiles when examining barriers to access and 

research. Limiting THC and THCA from patients only further imposes these barriers. While lowTHC, high-CBD extracts will no doubt help a great many patients, many more will be left without 

relief simply due to the bias against other parts of the cannabis plant. 

Many of the families who submitted their stories do not wish to have their names attached to their 

stories. This is understandable, to admit success as a medical cannabis patient is to admit that you 

are breaking federal law. This same force prevents many patients from even seeking this 

potentially lifesaving therapy. Nobody should be forced to choose between breaking federal law or 

going without potentially lifesaving medicine. 

Physicians should have every tool available that can help them treat their patients. If a licensed 

physician determines in their medical opinion that the potential benefits of a therapy outweigh the 

potential risks, the patient should be able to undergo that option. We urge the Committee to 

explore these options. ASA supports the Compassionate Access, Research Expansion, and 

Respect States (CARERS) Act, (S.683) because it addresses federal barriers to the full range of 

cannabinoid profiles. 

National Office California Offic~ 

18CilVernon S.t NW, Swt~ 100, Washmgton DC 20009 770 L Stree-t. Suite 950, Sarr~me'lto. CA 95814 

PHONE: 202 85? 4772 FAX· 202.8)7 <1271 PHONE 916.449 3975 

General Information 

WEB· wwvJ.Ar.wncan~ForSafeAccess.org 

TOLLFREE 888-929-4357 
215 

We thank you for receiving these stories and considering them as you contemplate means to lift 

the federal barriers to cannabinoid therapy. 

Sincerely, 

Michael Liszewski, 

Government Affairs Director 

National Office California Office 

Beth Collins, 

Communications and Outreach Director 

General Information 

1806 Vernon St. NW, SUite 100, Washington DC ?0009 770 l Street, Swte 950, Sacra'Tlento, CA 9':\814 WE~: WY.JW.Am~nransFcr'iJft>Arre<;s org 

PffONE: ?02 857.11272 FAX: 202.8'17 4171 PHONE· 916 449.3975 TOlLFREE· SBS 929·4367 
216 

February 24, 16 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

Medical cannabis has helped my 6-year old son's epilepsy in ways that FDAapproved pharmaceuticals have failed. He had tried 6 different FDA-approved 

anti-seizure pharmaceuticals, in addition to the ketogenic diet and steroids. He 

saw 8 different neurologists, including those at Johns Hopkins world-renowned 

Pediatric Epilepsy Center and Massachusetts General. He used to take 12 

different pills every single day. 

All of those solutions did not help stop the seizures. He had stitches 7 times from 

seizure related injuries. Since he was diagnosed at age 1 1/2, he has had over 

14,000 seizures. 

When my son went on CBD-oil, we noticed an improvement in learning, but no 

change in his seizure control. Eight days after starting THCa, my son went 

seizure free and continues to be seizure free for 15 months and counting. He has 

been seizure free and pharmaceutical free for a week now. His education team 

and everyone who knows him are truly amazed with his improvement in his 

ability to learn and participate in the world. 

Our state has a legal medical cannabis law that is being implemented. We look 

forward to being able to give our son the fife-saving THCa oil through the legal 

program. We hope the Federal government will also allow access to this 

treatment that does not make our son high. We hope to be able to travel outside 

the state without fear of persecution. 

Think for just one moment what it would be like to walk in our son's shoes and 

please open your hearts and your minds to allow him to get legal, safe access he 

needs as soon as possible to this life-changing medicine. 

Sincerely, 

Mom of 6-year old with epilepsy 

CC: Sen. Tom Carper 
217 

[date] 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Aflairs 

328 Hart Senate Oflice Building 

Washington, DC 20510 

Dear Chairman, 

I am writing you asking for medical cannabis to be rescheduled so I can get a law 

passed to get this medicine here in Iowa. I sufler from chronic back pain and I was 

diagnosed with scoliosis. I sought out other forms of relief and cannabis eased my 

suffering. This started was back in 1996 and here it is 2016 and its still an on going 

issue. I used mostly the dried flowers as my medicine to relief my pain. 

The issues with the current state and federal laws regarding medical cannabis and 

cannabis in general is not only that we have people in jail right now with less than a 

gram of cannabis, there is no room for the hardened criminals, but also I have noticed a 

lot of people are leaving their state of Iowa tor extended periods of time and even for 

good because cannabis is not recognized as a legitimate and helpful medicine. 

I am able to attest that this medicine does work, and if you and the people in power see 

the benefits of this simple but helpful plant, not only health wise but the revenue that 

comes from it, I don't know exactly why it has not been already approved. 

Do the right thing and stop the suffering in Iowa. 

On a side note July 2014 to June 2015 in Colorado medical cannabis netted almost $70 

million dollars in taxes .... Take that into consideration as you make this VERY 

IMPORTANT decision to save the lives of people who are suffering, and expand the 

range of people who could be saved from this. 

Thank you for your time, and I hope you make the right decision not just for me but for 

all Iowans who are suffering. 

Sincerely, 
218 

Chris Albright 

Boone, Iowa 

CC: Sen. Tom Carper 
219 

2/23/2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

Dear Chairman, 

My name is Janel McDaniel. I am a 34 year old seizure 

patient who didn't develop this until I was 31 years old. 

Think about it from my life. I drove, went to theme parks, 

was completely healthy until that fateful morning in July 

2012 when my life forever changed. When I first got out of 

the hospital, I was completely sedated for16+ hours a day. 

The doctors said "my brain needed to rest" until we knew 

what happened. I was on 4 medications to keep me 

asleep. I wasn't allowed to be left alone. I couldn't care for 

my young kids. We had to sell our house and move in 

with my in-laws so someone could watch me at all times. 

The seizures were horrible. We had to give up our 

independence as a family, give up our home, and not to 

mention the burden financially and emotionally seizures 

cause! 

Fast forward 3 years later, I have been on 1 0+ medicines, 

all FDA approved. I have always worked in the medical 

field so I knew that I was "supposed to do exactly what the 

doctor said." I worsened. I couldn't move and would sleep 

for 24-48 hours after each seizure. My husband held his 

breathe wondering if this one would be the "final" one as 

nothing was helping. We removed stress, I couldn't work, I 

took my meds as prescribed, etc. Anything and everything 

the doctors suggested we did to try to make them stop. 

After all, I have no family history or contributing factors as 
220 

to why they started. I still worsened and the severity 

worsened to where I was told last year that I have a 45-

50% of dying in my sleep if we can't get control. So more 

meds were added and back into the hospital I went. 

I was then introduced to medical cannabis. At first, I was 

skeptical. After all, my medical training told me different 

and I've never even smoked a cigarette, much less done 

any drugs. It was a far concept for me. But when you are 

faced with watching your kids grow up or dying, I chose to 

be here as long as I can. I have tried 4 strains of cannabis 

oil. The 2 that can be shipped didn't control me. After all, 

they were developed with kids in mind and that's ok. I then 

tried a strain with an 18:1 ratio out of CO. I felt amazing! 

So I started weaning off the Keppra 2000mg, Trokendi XR 

600mg, Valium 20mg, and Vimpat 600mg that I took daily. 

Amazing enough, I was able to wean off ALL meds and 

still have seizure control on R4. Then I couldn't get 

access to R4 any longer so I found a place similar in CA. 

This involves driving to CA, breaking the law, and no 

testing but it was the strain I need so I had to try. 

The first month, I had a few seizures. The first thing I 

noticed was my short term memory returned and people 

said I wasn~ repeating myself like I was. I felt better but 

not 100% because I was having break through seizures. 

My type of seizures changed immediately. I went from 5+ 

minute seizures where I was unconscious to seizures less 

than 20 seconds and the major difference is I could hear 

people in the room, although I still couldn't see them. This 

helped comfort level wise since I never knew before. I 

remember thinking this is a miracle! I was still having some 

break through seizures so it was recommended that I add 

thea. I am one of the few that regular the as a rescue 

triggers cluster seizures in me. I felt like I was normal 

again. Day after day passed after starting the thea with the 

oil. 30 days seizure free came!! I was for sure I would drive 

again and be able to go back to nursing. After all, I can't 
221 

be running an IV on someone and have a drop seizure. I 

was able to return to work, although not nursing yet, and 

most importantly, I was able to function as a mother, the 

only true title I ever wanted in life. 

FDA approval for medicine is something I've learned 

means nothing. As a nurse that worked Pediatrics, I see 

what they are doing. The FDA approved Tamiflu for ages 2 

weeks old and up but yet you can't give Tylenol before 6 

weeks old and Motrin before 6 months old! Then 

OxyContin for 11 year olds? A while back Loratab was not 

recommended for kids because of the respiratory 

depressant effect yet OxyContin? OTC cough meds are 

still not recommended for under age 2 yet Tamiflu is? That 

is unbelievable. Then I started researching. Cocaine and 

methamphetatine are schedule 2!! Yes you read that 

right!! I struggled as a nurse to go against what I was 

taught but it opened my eyes to how twisted things are. Do 

you know how things are removed from the FDA 

schedule? People die! That's insane!! 

I can't fathom how people can't understand. Nicotine and 

alcohol kill hundreds of thousands a day. Cannabis-0. 

Now Georgia strips in state cultivation, which was 

someone like mine last hope. See, my last batch from CA 

was bad. It made me violently sick! I can't even tell you 

everything that happened because I don't remember until 

5 days later. But I'm desperate. Desperate to live to watch 

my kids grow. Moving out of state is not an option for me. 

I share custody of my oldest child with my ex-husband and 

I won~ leave my son behind. So my choices are to keep 

breaking the law (which I have never done before now), 

stop cannabis oil and go back to how I was, or beg for 

mercy! I chose mercy and grace. I respect the law but I 

love my kids. How do you choose? I've now had the 

experience of a bad batch of cannabis and I never want to 

feel it again! It was scary. 
222 

No medicines controlled me, but cannabis has given me 

longer periods of normalcy. Normalcy-a word that so many 

take for granted yet I have to pray and strive for! Life, 

liberty, and pursuit of happiness. Inalienable rights we 

were given by our founding fathers. Why am I and so 

many other being denied this by keeping us sick with 

seizure meds? 

I didn't ask to get sick but i ask for the medicine to help 

me. Allow me to be an adult. Don't let my worst fear of 

death happen when there are other choices. Fear of 

change affects us all including me. But this is a change 

that saves lives! All laws were meant to be re-examined. 

Please reconsider. Don't wait until it's too late. 

Sincerely, 

Janel McDaniel 

Flowery Branch, GA 

CC: Sen. Tom Carper 
223 

February 22, 20 !6 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

I am a resident of Massachusetts and I am writing today about medical marijuana and legalization. I 

have researched medical marijuana since it became legal in Massachusetts. I am a chronic sufferer of 

pain, severe muscle spasm, nerve injury, and a long list of allergies to things in the everyday 

environment including mold, mildew, dust mites, and multiple-chemical sensitivity to name a few. In 

2014, as a direct result of too much prescription medication for pain I landed in the hospital ER ICU 

overnight. That was a wake-up call that led me to start a dialogue with my long-time personal physician 

about the possible benefits of treatment with medical marijuana. One of the things that I learned in my 

personal research was about the wide variety of medical and quality of life benefits to cannabis. 

Nonetheless, I have come to realize that the benefits and uses of cannabis do not always qualify for a 

prescription. As a law abiding and upstanding citizen, I believe that this makes removing legal barriers 

to medical and scientific research critical. As a nation, we seek to improve the quality of life for all 

citizens, and insure our laws truly reflect public policy throughout America. However, here is how the 

current conflict between state and federal laws regarding medical cannabis affects me, I have learned 

that even if my doctor prescribed medical marijuana, or when it becomes legal under the current 

legislative initiatives in Massachusetts I still would not have access because I live in Federal public 

housing. My lease is subject to Federal laws concerning marijuana, and my understanding is that would 

give my housing authority a cause to evict me for marijuana use or possession. 

That is why I am writing in support of Americans for Safe Access and submitting my story for them to 

present at the hearing on "Connecting Patients with New and Potentially lifesaving Treatments." It is 

clear that the American people are committed to legalization and reform. The list of states legalizing 

cannabis for personal and medical use is steadily growing. The legislative direction of these states and 

the majority of their citizens make it clear that the current legal status of cannabis at the Federal level is 

at odds with the vast majority of Americans and their elected officials. 

Moreover, the medical communities from the doctors who recommend and prescribe cannabis to our 

top Federal regulators are making it clear that cannabis has a long and growing list of medical 

applications from opiod treatment to combating deadly seizures in adults and helpless children. A 
224 

global community of researchers and doctors is producing an endless flow of data proving that cannabis 

is an untapped resource that we have only just begun to exploit to its fullest potential. 

Shortly after my hospital stay, I lost my job. Over the past two years, I have completed a training 

program through my state unemployment assistance office. Now that I am re-entering the job market 

obtaining the treatment of my choice would leave me fearful of losing my job because of medical 

cannabis treatment. The existing conflict between state and federal requirements leaves employers 

with no choice except to report and terminate patients for cannabis use. So please, look at the facts 

relative to the legalization issues and honestly weigh the cost of legalization with the benefits to society, 

patients, and the Government's interest. We are the government's ultimate beneficiary or victim in the 

decisions that you make to support, or not support, legalization and reform. 

The things that I have learned about the benefits and uses of cannabis over the past years have made 

me an advocate for legalization. I follow the battles of ordinary law abiding hard working Americans as 

they struggle with outdated laws, misguided law enforcement, and misinformed bureaucrats. I cannot 

express how sad it makes me to read story after story about children and elderly patients losing their 

battles with illnesses that researchers have already proven are treatable with cannabis. I do not 

understand how my federal government can argue endlessly on principle while children and their 

parents in states across America suffer without treatment as doctors and legislators plead with the DEA, 

FDA, and Congress to act. I hope that you will act in support of Federal cannabis legalization for me, and 

millions of Americans. It is time to stop the needless suffering, it is time to stop ruining American lives, 

and it is time to stop ruining American families. 

Sincerely, 

Curtis Chambers 

Wayland, MA. 

CC: Sen. Tom Carper 
225 

February 24, 2016 

Senator Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

This letter is to ask for your help in addressing the FDA's barriers to accessing 

medical cannabis for seriously ill patients and patients with chronic conditions--

including epilepsy--and their families. 

Our 11 year old daughter Rachel has intractable (drug-resistant) epilepsy She 

has both big seizures that don't end on their own (every one of her big seizures is 

a medical emergency necessitating use of a rescue medication--Diastat, a 

Federal Schedule IV controlled substance), little seizures (atypically atypical 

absence--otherwise known as dialeptic seizures), a continuous spike in her 

frontal lobe, and two kinds of subclinical seizures. She can have up to 50 

seizures a day of the sort we can see; her subclinical seizures--which we can't 

see--are in the too many to count range. 

Rachel is under the very best of care--being treated by an experienced 

epileptologist who is also a medical school professor and who works out of a 

Children's Hospital with a Level 4 Epilepsy Center (the highest rating). Despite 

this excellent care, Rachel's epilepsy has not been able to be successfully 

controlled by current antiepileptic drugs (AED's). Her very experienced 

epileptologist calls her his poster child for what can go wrong with AED's. Three 

trials of AED's have resulted in a classic drug eruption, the beginnings of DRESS 

Syndrome (which carries a 10% mortality rate), and severe behavioral issues--

simply put, under one of the AED's our normally very sweet, loving child became 

hostile, standoffish, and aggressive (yelling at us, throwing things at us, and 

literally attacking us physically). The fourth trial of an AED (her current 

medication--which is a Federal Schedule V drug) has resulted in long term 

severe nausea and intestinal pain. None of these drugs stopped her seizures. In 

fact, each one has simply exacerbated Rachel's seizures to varying degrees. 

Because of her AED related rashes, many other AED's can't be tried because of 

the very real risk (documented with medical studies) of cross-sensitivity and the 

likelihood that she'll develop another serious rash--perhaps one with an even 

higher mortality rate. Her doctor says her case is very unusual, very complex, 

and very challenging. Despite all her seizures, she is a very normal, very bright, 
226 

very social, and very upbeat little girl. She just wants to be able to have a normal 

childhood and worry about normal childhood things. Cannabis could be so 

helpful in achieving that. 

Rachel's epileptologist has talked to us about about medical cannabis. Cannabis 

would NOT present the difficulties that the other AED's present in terms of 

rashes. Its mode of action is totally different from other AED's. It helps the brain 

find the balance between excitation and inhibition--and unlike normal AED's, 

cannabis works through secondary pathways in the brain, not primary ones. It's 

a gentler, kinder medication. But we can't access cannabis in the state of 

Alabama at this point without fear of criminal prosecution. 

We have no idea what the future holds for Rachel. We've already pursued 

genetic testing through Baylor University; they found no explanation for her 

epilepsy. Rachel will begin more extensive testing this summer to see if she 

could be a surgical candidate, but only 2% of children prove to be good 

candidates. We are starting to realize that if her epilepsy continues to be 

intractable that we may have to consider moving to a state where cannabis can 

be more easily accessed. This would be very sad as my husband is a law 

professor who would have to leave his job; our family and friends are here in 

Alabama where we've been for nearly 30 years. The thought of trying to smuggle 

bottles home across state lines is disturbing. We don't want to have to break the 

law to help our child have a chance at normal life. 

Of course, if medical cannabis were rescheduled so it were no longer a Schedule 

I drug, it would help immensely. Families like ours need your help. Please help 

us access cannabis for our children! 

Sincerely, 

Desiree Smolin 

Birmingham, Alabama 

CC: Senator Tom Carper 
227 

February 24, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

Our family moved to Colorado in March of 2013. My husband and I had reached 

the end if Emily's pharmaceutical rope. She had failed over 14. There were no 

more meds that we could try. Her neuro said this is the best we can do. 

The best they can do was four antiepileptic drugs scheduled, a special highly 

control diet called the ketogentic diet, and 3 prn (as needed) benzodiazepines 

that she took daily. Emily was only 3 and was having over 100-200 seizures per 

day. The worst made her oxygen plummet to the 50-60's and she would gag and 

vomit as she violently flailed on the living room floor. 

She was in a palliative care program through our local hospice. She was not a 

brain surgery candidate. We had no hope. 

When we saw kids having success on cannabis oil in Colorado we knew we had 

to try. Bankrupt, jobless, and scared we moved. We were alone and isolated from 

family. 

It was so hard on us but our love for our beautiful girl outweighed our fear. 

Emily's worst seizure stopped on April 2, 2013 with her first dose of cannabis oil. 

It was a 14:1 ratio of cbd:thc. As time went on the company who made Emily oil 

kept increasing the ratio to wean out the the so it could be classified as hemp and 

be shipped. Emily lost more and more seizure control as the ratio got higher. We 

started adding the back in and regained the seizure control that we lost. 

Fast forward to 3 years later. Emily's seizures are great. Less than 10-15 split 

second seizure per day. She is no zero seizure medications. Just cannabis oil. 

She doesn't sleep well in spite of trialling many prescription sleep medications. I 

decided to try just the at night to see if it helped her sleep. It helped her sleep a 

little better but the biggest thing we noticed was her seizures stopped! After the 

first week my husband and Emily's day nurse kept looking at each other in shock! 

Did she just go a week with out a single seizure?! She went 28 days before she 

had a small little myoclonic jerk. She is averaging 2-3 weeks between seizures 

now and they are usually just a split second jerk. 

Emily now only takes a small dose of a high the low cbd oil each night. 
228 

While this is amazing and her developmental progress has been great lately too 

it's hard because we can't take her the oil out of the state. Colorado is our island 

now. When she used "hemp" oil we could travel but now that hemp didn't help we 

are forced to stay put if we want to control her seizures. 

I wish everyone had safe access to the full spectrum of cannabis oil. Had we not 

been in a legal state and we able to try a high the oil Emily may not be doing as 

well as she is. 

I am so thankful for her medication. 

Sincerely, 

Erica Rollins 

Colorado Springs, Colorado 

CC: Sen. Tom Carper 
229 

February 24, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

Jennifer Collins of Fairfax, Virginia is 16 years old and suffers from Jeavons syndrome and can have up to 

300 or more absence seizures a day. Her seizures would often cluster and cause tonic clonic seizures as 

well. She tried and failed 15 anti-epileptic medications, but either they didn't work, or the side-effects 

were unbearable. 

These side effects of her medication included rages, cognitive functioning issues, depression, weight 

gain, and ovarian issues, to name a few. Her rages, caused by her medication, had gotten so bad, that on 

several occasions her parents had to call 911 to help me subdue her. This was not the happy-go-lucky 

child everyone knew and loved, and it was devastating for her. She couldn't control it, and she wanted 

to hurt herself. 

Out of options, her mother spoke with Jen's neurologist about trying cannabis as a treatment, and he 

said, "If I could legally obtain this for you here, I would. It is worth a try." So, in December of 2013 to 

Jennifer and her mother moved to Colorado, separated from her father, sister, extended family, friends, 

and support community to give her the opportunity to try cannabis. 

The Collins family didn't make this decision lightly. They left to give Jennifer the opportunity to find 

relief from her seizures, and the harmful side effects of her medications through medical cannabis. They 

stayed in Colorado for on year. 

While in Colorado, Jennifer started taking non-psychoactive Tetrahydrocannabinolic acid (THCa) oil, a 

tiny amount administered by a syringe under her tongue three times a day. Not only did her absence 

seizures lesson drastically and her tonic clonic seizures disappear, but she was able to lower the doses of 

her pharmaceutical medications. The rages stopped, the thoughts of suicide stopped, she lost the 30 

pounds she had gained upon starting medication, and her cognition and school grades improved. 

The stress of living apart from her father, sister, friends and family was too much for Jen, who fought so 

bravely to fit in and make friends in a somewhat unwelcoming environment. So the family was again 

faced with a heart breaking decision. They chose to go back to Virginia and fight for the right to take her 
230 

oil in Virginia. They and put their faith in their lawmakers to pass a law that would allow her take the 

medicine that helps her in the home where she grew up, surrounded by the people that love her. 

Jennifer fought hard for the bills that Senator Dave Marsden and Delegate Dave Alba wrote to give 

people like her with intractable epilepsy the ability to take Cannabidiol oil (CBD) or THCa to treat their 

seizures without fear of prosecution. The bills were passed and signed into law by Governor Terry 

McAuliffe in February of 2015. 

Unfortunately, the current law does not provide for any form of production and distribution of the 

cannabis oils Jen and others like her in Virginia need. So, once again she is working on helping pass 

Senator Marsden's bill, SB701 that will allow tightly controlled production of CBD and THCa oils in the 

state. In addition, she has been speaking to members of the U.S. Congress trying to get the Senate and 

House CARERS Act bills passed. The CARERS Act would, among other things, reschedule cannabis to 

schedule 2. It is now a schedule 1 drug (reserved for the most dangerous drugs that are deemed to have 

no medicinal value) and remove some of the barriers to important research on this plant. 

Jennifer has been an inspiration to many people, especially those suffering from intractable epilepsy 

who need this medication. She has not had a tonic clonic seizure since starting cannabis oil two years 

ago. In addition, she was able to wean her pharmaceutical medications down to 1/12 of one, and 1/3 of 

the other and no longer needs rescue medication. Jennifer should not have to fight so hard to legally 

take a medicine that has improved her life so much. 

Sincerely, 

Beth Collins 

Fairfax, VA 

CC: Sen. Tom Carper 
231 

February 22, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

I suffer from Severe Chronic Pain due to Degenerative Disc Disease, Cervical Spondylosis, 

Stenosis and Arthritis. I have had 5 spinal fusion surgeries (fused from C-4 to T-5) and also 

have a spinal cord stimulator implanted in my neck, and it's battery pack in my back. None of 

these surgeries have helped with my pain. Opioid "Pain Killers" and Muscle Relaxers have 

also been useless and caused terrible side effects, such as Agitation, Depression and 

Disruption to Sleep due to violent muscle jerks. 

I have been to Surgeons and Pain Management and All have told me "There is Nothing More 

We Can Do For You". I searched the Internet for any answers and the only thing I found, over 

and over was Medical Marijuana. I have Never used an Illegal Drug and had never even gotten 

Drunk. 

I am a 45 year old Husband and Father of 2 Wonderful Teens. I am Retired on Disability 

because I can no longer sit at a computer without being in sheer agony. This has placed me in 

a very Depressing and Desperate Situation. For the past 8 years, I have been unable to take 

part in many family activities, missing out on trips, concerts and vacations, even Movies became 

too painful to endure. 

Last year, I went to one of my Doctors and discussed Medical Cannabis and was told that it was 

being worked on in Maryland but could be over a year before Dispensaries are opened. One of 

the Nurses Bluntly asked "Why don't you just try it? Then you would know to pursue it when it is 

available." I took her advise and purchase a very small amount to see for myself. I only took a 

few puffs and soon was feeling relaxed pain relief!! For the first time in over 7 years I 

experienced ZERO Pain while sitting in my Recliner!! 

I never dreamed I would See Marijuana (Cannabis) as a "Medication" but after So Many Failed 

Procedures and Pharmaceuticals that had horrible side effects, there is No Other Option. 

Medical Cannabis is not yet fully Legal in Maryland, but is the Only thing that has given me 

Hope! Decriminalizing it is all fine and good, but I still have to FIND my "Medicine" in a not so 

safe way, and buy tiny amounts that are quite expensive. There is no way to know what is in 

what I get, let alone, if it is a strain that will help me. Even though todays batch worked, the next 

time may be something totally different. I have dealt with ones that make my heart race to ones 

that make me extremely lazy and some that give very little relief. Spending that kind of money 

on a useless strain is very frustrating. I look forward to the day a dispensary opens here so I 

can get the High CBD Strain that I need, but for now, I will do what I Need to do to achieve 

relief. 
232 

Last year a dear friend of my family committed suicide. He was a 71 year old Husband and 

Father that was suffering from advancing stages of Parkinson's Disease. I admitted to my wife 

that I, unfortunately, could understand the mentality that brings a person to that awful decision, 

because I had been Way Too Close to that Edge. Cannabis Pulled Me Back From That Edge'! 

There was No Hopei! I am only going to get worse. Doctors have failed me. Surgeons have 

failed me. Pain Medications have failed me, causing horrible side effect, such as severe 

myoclonic jerks, from narcotic pain medicine and muscle relaxers. While falling asleep, I would 

Jump and smash my hand into my nightstand or even hit myself in the face. I have also dealt 

with extreme mood swings that scared my family. Even Advanced Medical Technologies have 

!ailed me. The Spinal cord stimulator did not offer any relief to the worst areas of my pain. 

Being Repeatedly Told "There is Nothing I Can Do For You" takes a person to a Terrible Mental 

State ... 

Medical Cannabis has allowed me to go out for a couple hours at a time before I am unable to 

stand the pain. I was recently able to attended my Daughter's Marching Band Competitions 

without being in excruciating pain. I have also been able to go out to restaurants and movies 

again!!! I am getting to Live Again and my wife told me: "I HAVE MY HUSBAND BACK!" All from 

something I Absolutely Despised'!! Cannabis IS the Miracle Medicine everyone has been 

looking fori! The Government needs to Recognize That!! 

Sincerely, 

Stephen T. Qualey 

Millersville, Maryland 

CC: Sen. Tom Carper 
233 

February 21, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

Hi my name is Raymond F Smith I had a bad accident a few yrs back in which I 

lost my 6 yr old son. I accidentally backed over him and took his life. I was 

devastated. I used marijuana for post traumatic stress syndrome. It was a life 

saver as I was raising my 2 boys by myself at the time. It helped me forget about 

everything but what was important at the time. It helped me run my business and 

preform my daily duties with out losing it and the repeat of that days occurring 

nightmare. PTSD is for real and marijuana was the only thing that eased the pain 

of my loss. 

The side effects of marijuana are not physically disabling and yes you can still 

function fully and get through your daily lives and be vary productive. Marijuana 

is a God send. It is all natural and the chemical in it matches a chemical in our 

brain, and by being able to enhance that chemical gives instance release from 

the pressure of the bad thoughts in your mind. I thank God for this wonder drug 

and I have had to use it illegally thus causing me to have a run in with the law 

because of it being illegal. I live in Burlington Iowa and pray that the legislators 

will get on board and read the research that is proven by using this natural drug. 

Sincerely, 

Raymond F Smith 

12673 Flint Bottom Rd Burlington Iowa 52601 

CC: Sen. Tom Carper 
234 

Tuesday, February 23, 2016 

Sen. Ron Johnson 

Chairman 

Senate Committee on Homeland Security and Governmental Affairs 

328 Hart Senate Office Building 

Washington, DC 20510 

Dear Chairman, 

It is with great honor that I have the opportunity to share with you the success my daughter has had with cannabis. At 6 

weeks old, our sweet Magdalyn began having seizures. By 4 YS: months old, we were told she probably wouldn't live very 

long. She tried pharmaceutical after pharmaceutical, with minimal impact on her seizures, yet devastating to her 

development. Statistically, she had less than .8% chance of finding a pharmaceutical that would effectively treat her 

seizures. At 17 months, out of options, we decided to move across the country. We relocated to Colorado, away from 

family and a tremendous support system at our church in Tennessee. That was the toughest but best decision we ever 

made. Though she has yet to find complete seizure freedom, she is thriving. 

When we relocated, Maggie had over 500 seizures per day and significant global developmental delays. Nearly any 

movement she made was a seizure of some sort. She was critical. We saw an instant response to starting her on 

Charlotte's Web oil. Her digestion picked up and she began to vocalize more. We continued to slowly wean her off the 

pharmaceuticals. We added THC-A oil to her regimen and her cognition picked up. Over the past 2 years, she has been 

able to express herself, develop more and more control with her body, and her seizures have decreased by over 80%1 

That is phenomenal given her prior critical condition. Most recently, we began using a transdermal THC patch that has 

provided even further seizure relief. 

After substantial exposure to both pharmaceuticals and supplements, as well as over 2 years of administering cannabis 

to our daughter, I am convinced that cannabis works much more like a supplement than a pharmaceutical. The 

treatment continually needs to be varied in order to support her body's systems, versus chemically altering her body. It 

is an individualized medicine. 

Unfortunately the federal and varied state laws create a major predicament when wanting to visit family and friends 

throughout the country. It is outlandish to me that we are limited in our ability to travel and could face prosecution 

solely for helping our daughter find more seizure relief. 

CC: Sen. Tom Carper 

We are beyond blessed for the opportunity that we have had to simply enjoy life with our 

now 3 Yz year o!d daughter. The reality that she is in preschool this year, and we haven't 

had to bury her yet is a testament to just how beneficial cannabis oil is. As a family, we 

continue to pray for legislators' clarity and education on this issue. 

Sincerely, 

Rachael Selmeski 

Castle Rock, CO 
235 

Post-Hearing Questions for the Record 

Submitted to Ms. Darcy Olsen 

From Senator Claire McCaskill 

"Connecting Patients to New and Potential Life Saving 

Treatments" 

February 25, 2016 

Q. How can the FDA improve the Accelerated Approval process to ensure 

access to life-saving treatments, while also maintaining public safety? 

Under the Accelerated Approval process, the actual research time may be 

shorter than the standard FDA approval process. However, Accelerated 

Approval does not reduce the time delay in the negotiations that take place 

between the sponsors and the FDA on what is required to be considered for 

a review. This process can take many months or, in some cases, years. (This 

time delay is not officially tracked by the FDA.) 

The obstacle seems to be the FDA interpretation of what is sufficient to be 

considered for an acceptable NDA filing, as well as what constitutes a 

positive review under the Accelerated Approval pathway. In order to further 

improve the Accelerated Approval process, steps should be taken to reduce 

the time spent on the negotiations that take place between the sponsors and 

the FDA on what is required to be considered for review which does not 

contribute as significantly to patient safety (compared to actual safety 

testing). The parameters for what is sufficient for an NDA filing and what 

constitutes a positive review could be defined legislatively, giving both the 

FDA and NDA applicants clear parameters for both. 

Another distinction from the standard FDA approval process is that, under 

Accelerated Approval, post-marketing study of clinical outcomes must be 

conducted and must show meaningful therapeutic benefit over existing 

treatments (or placebos). If, according to the FDA, a meaningful 

therapeutic benefit is not shown, the drug can then be rejected. 

The ability of the FDA to reject a drug post-approval under the Accelerated 

Approval process should be more closely examined. Possible reforms could 

include creating a less-restrictive definition of "meaningful therapeutic 
236 

value." This would not impact patient safety but would offer physicians 

more available treatments for patients. 

A particular treatment might be rejected because it only helped 10 percent 

of patients. But rapid advances in medicine might now show, for example, 

that the same treatment helping So percent of patients with a specific 

genetic makeup. 

Distinct but related designations that are intended to accelerate the FDA 

drug approval process include Fast Track, Breakthrough Therapy, Priority 

Review, and Accelerated Approval. 

Q. How have fast tracked drugs been specifically beneficial to adults and 

children with chronic conditions? 

Of the 76 Fast Track drug approvals that occurred from 1998 through June 

1, 2010, more than half (43) of the approvals were for the treatment of HIV. 

While most treatments are not specifically indicated for children (resulting 

in the vast majority of treatments for children prescribed off-label), only 

one approval during this time period was for pediatric patients (relapsed or 

refractory acute lymphoblastic leukemia). 

Of the six novel drugs approved under Accelerated approval in 2015, five 

were for cancer diseases (of which there are more than 200): Alecensa 

(advanced (metastatic) ALK-positive non-small cell lung cancer), Darzalex 

(multiple myeloma), Farydak (multiple myeloma), Ibrance (advanced 

(metastatic) breast cancer), and Tagrisso (advanced non-small cell lung 

cancer). 

One question that deserves further investigation is whether the Fast Track 

designation is being under-utilized for rare and terminal diseases (other 

than cancer). 
(237) 

1The prepared statement of Senator Johnson appear in the Appendix on page 281. 

EXPLORING A RIGHT TO TRY FOR 

TERMINALLY ILL PATIENTS 

THURSDAY, SEPTEMBER 22, 2016 

U.S. SENATE, COMMITTEE ON HOMELAND SECURITY

AND GOVERNMENTAL AFFAIRS, Washington, DC. 

The Committee met, pursuant to notice, at 10:04 a.m., in room 

SD–342, Dirksen Senate Office Building, Hon. Ron Johnson, Chairman of the Committee, presiding. 

Present: Senators Johnson, Paul, Lankford, Ayotte, Ernst, Sasse, 

Carper, McCaskill, Tester, and Peters. 

OPENING STATEMENT OF CHAIRMAN JOHNSON 

Chairman JOHNSON. Good morning. This hearing of the Senate 

Committee on Homeland Security and Governmental Affairs is 

called to order. I want to welcome all of our witnesses and all of 

our audience members. 

This is the second hearing we are holding on issues related to a 

bill I introduced called ‘‘Right to Try,’’ and I will ask unanimous 

consent (UC) to have my written statement entered in the record.1

I will keep my comments brief because I want to show about a 

31⁄2-minute video as my true opening statement. 

On Saturday, I attended a Walk for Amyotrophic Lateral Sclerosis (ALS) in Appleton, Wisconsin. I think that so many of us first 

heard about ALS as Lou Gehrig’s disease, and then later, on Tom 

Watson’s caddy. And, in my own personal experience, a member of 

our Lourdes High School family, Doug Perzorski, was diagnosed 

with ALS. His wife, Meg, and their children—unfortunately, we 

lost Doug a couple of years ago. 

And, then as a U.S. Senator, a couple of years ago, I met a young 

mother of three, Trickett Wendler, and I had just met with the 

Goldwater Institute, and I knew of their efforts trying to pass 

‘‘Right-to-Try’’ bills in States like California and elsewhere. Just by 

mentioning my interest and my support for ‘‘Right to Try,’’ tears 

started streaming down Trickett’s face. 

On Saturday, I met a number of patients fighting ALS, and their 

families fighting with them. There was a family—and three of the 

siblings were suffering from Familial ALS (FALS). One had had it 

for 15 years—it is a slightly different condition when it is that kind 

of hereditary ALS. 
238 

We have Matt Bellina. We also have Frank Mongiello, who provided such incredible testimony when we had our press release on 

this, and so, Frank, welcome to you. In a nutshell, this effort—if 

it were up to me, I would not call it ‘‘Right to Try.’’ I would call 

it ‘‘Right to Hope.’’ 

And so, what I would like to do now is offer a 31⁄2-minute video 

by Dr. Ebrahim Delpassand. I consider Dr. Delpassand a whistleblower. He is a courageous doctor. He is board-certified in nuclear 

medicine. He has a residency at Baylor, where he had his residency 

at Baylor College of Medicine, and was formerly at the University 

of Texas MD Anderson Cancer Center (MD Anderson) for 12 years, 

where he was the chief of clinical nuclear medicine. In 2003, he 

joined the private oncology center Excel Diagnostics. He is an adjunct professor at the University of Texas Medical Branch—a highly qualified doctor. 

In 2005, he began investigation for a new drug to treat 

neuroendocrine cancer—carcinoid cancer. A newer version was 

later available, which meant there was another approval process 

from 2007 to 2010. In August 2010, he began treating patients with 

a therapeutic agent called Lu–177 Octreotate. In March 2015, he 

treated 143 of the 150 patients allowed. He requested the Food and 

Drug Administration’s (FDA’s) permission to expand the trial and 

add another 100 patients. By this point, the manufacturer had 

completed its multicenter trial and was in the follow-up phase to 

observe the progression of the condition. In other words, the clinical trials had completed enrollment. The FDA cited commercialization concerns in denying the request. 

So, I would like to just play the video now. 

[Videotape shown.] 

Now, I consider Dr. Delpassand a hero. I consider him a whistleblower. He is taking great risk operating under Texas’ ‘‘Right-toTry’’ law, trying to save his patients’ lives, but also giving and offering his patients hope. 

Now, I spoke with the representatives of the ALS community, 

here. Obviously, Dr. Delpassand is dealing with cancer patients. 

We also have Jordan and Laura McLinn. Jordan has Duchenne 

Muscular Dystrophy (DMD). Now, I was overjoyed on Monday to 

find out that the FDA finally approved a drug to give these little 

boys with DMD their right to try—their right to hope. So, that is 

really what this is all about. 

Now, next week, I will be asking the U.S. Senate to approve the 

‘‘Right-to-Try’’ bill under a unanimous consent request. We have 

cleared it on our side—and, obviously, one of the goals of this Committee is to provide powerful testimony and to convince every U.S. 

Senator, if they are not willing to cosponsor it—I would certainly 

love their cosponsorship of this very simple bill that just allows 

these State ‘‘Right-to-Try’’ bills to operate and that allow heroes 

like Dr. Delpassand to give their patients hope. If my Democratic 

colleagues and other Republican colleagues that have not cosponsored it are not willing to cosponsor it, please do not object so we 

can pass this bill and so we can give these patients and their families the right to hope. 

With that, I will turn it over to Senator Carper. 
239 

1The prepared statement of Senator Carper appears in the Appendix on page 282. 

2The FDA Fact sheet submitted by Senator Carper appear in the Appendix on page 314. 

OPENING STATEMENT OF SENATOR CARPER1

Senator CARPER. Thank you so much Mr. Chairman and thank 

you for calling this hearing today. I appreciate your willingness to 

continue a conversation about what we all know is an important 

issue that is critical for Americans seeking access to potentially 

lifesaving treatment. I also want to thank you and your staff for 

the ongoing work that we are engaged in to try and move the ball 

forward and to find ways to help patients gain expedited access to 

experimental therapies, including through a forthcoming Government Accountability Office (GAO) report on these issues. I especially want to thank our witnesses. It is a great honor to welcome 

you here. I especially want to say to Matt Bellina, Lieutenant Commander (Retired), an A–6 pilot, Navy salutes Navy this morning. 

And, I am delighted to see you here. It is a real treat to meet you. 

I also want to single out, if I could, Andrew McFadyen’s 

wife, Ellen, and their son, Isaac, who is being treated for 

Mucopolysaccharidosis (MPS), and his brother, whose name is Gabriel. Gabe, it is nice of you to be here with your mom and dad. 

And, to all of our other witnesses that are here, thank you for 

joining us. It is great to see you. 

Before I begin my formal statement, I just want to take a moment and mention my appreciation for the Chairman for sharing 

the video that we have just seen and I look forward to learning 

more about this physician’s experience. My understanding is that, 

in what would seem to be similar situations, the FDA has approved 

over 99 percent of patient applications for expanded access to these 

new experimental treatments. In fact, I understand the FDA has 

even granted drug approvals based solely on expanded access data, 

even for drugs that may be in Stage II trials—or even in Stage I 

trials. The FDA, as you know, by law, is precluded from discussing 

the details of any drug under review, but, if the doctor that we 

have just heard from today were here, I would ask him why he did 

not appear to use the expanded access program, which has worked 

quickly and efficiently for so many patients and their doctors. With 

that in mind, I would like to ask unanimous consent that we place 

an FDA fact sheet2 on expanded access, along with the recently updated application form, in the record. 

Chairman JOHNSON. Without objection. 

Senator CARPER. Thank you. 

My understanding is the application form for expedited access is 

a form that previously took hours to complete, I have heard as 

much as 10 hours—maybe even more. The expedited updated application form, I am told, takes 45 minutes or so, which has been one 

of the barriers for folks to actually take advantage of this opportunity. 

But, today we are going to have an opportunity to hear from the 

FDA, State representatives, patients, loved ones, and other advocates on ways we could improve access to experimental medical 

treatments—something we all want to do. These individuals and 

their families have faced some of the most difficult and painful 
240 

challenges anyone could face. They deserve to be heard—and they 

deserve better access to experimental treatments. 

We will also have an opportunity today to review the Chairman’s 

legislation, S. 2912, which he has alluded to, the Trickett Wendler 

‘‘Right-to-Try’’ Act. I appreciate the intent of Senator Johnson’s 

bill—I think we all do—and I, certainly, support expanding access 

to experimental therapies for terminally ill patients. 

We must keep in mind, however, that there is, already, what I 

understand to be an effective framework in place at the FDA for 

giving patients access to experimental drugs while those drugs are 

still being tested. The agency has given an extraordinary level of 

attention to the requests of patients with life-threatening conditions. In fact, I am told it has approved, as I said earlier, more 

than 99 percent of requests for emergency treatment between 2010 

and 2015. The agency has also taken constructive steps to greatly 

simplify its application process and further improve and streamline 

patients’ access to experimental treatments. 

Despite the high approval rates and ongoing reforms, I understand that the FDA believes that more can be done and is continuing to work to further improve patient access to experimental 

treatments—and we applaud that. I hope to learn about some of 

those steps today, as well as some additional ideas for how to ensure that all patients in need have the information and the resources needed to access experimental medicines. 

For terminally ill patients and their loved ones, safe and effective 

treatments cannot come quickly enough. That is why we need to 

do everything we can to give patients, doctors, and the companies 

that make these drugs the tools they need to participate in clinical 

trials, utilize the FDA’s expanded access programs, and develop 

new treatments as safely, effectively, and quickly as possible. I 

hope that our Committee can help with these efforts and work with 

patients, health care providers, the pharmaceutical industry, and 

the FDA to ensure that all patients and their families can access 

safe and effective treatments as quickly as possible. 

Again, I want to thank our witnesses and their families for joining us today, and for your willingness to share your stories and put 

forward possible solutions to these challenging issues. 

Thank you so much. 

Chairman JOHNSON. Thank you, Senator Carper. 

I will note that the video that we played is just a condensed 

version of a 20-minute video that we will enter into the record and 

that will be available on our website. Dr. Delpassand wanted to 

be here—but he had a medical emergency, I guess, with his mother—so he could have answered those questions. 

It is the tradition of this Committee to swear in witnesses, so if 

you will all rise and raise your right hand. Do you swear the testimony you will give before this Committee will be the truth, the 

whole truth, and nothing but the truth, so help you, God? 

Mr. BELLINA. Yes. 

Mr. CALDERON. Yes. 

Mr. NEELY. Yes. 

Mr. GARR. Yes. 

Mr. MCFADYEN. Yes. 

Chairman JOHNSON. Thank you. Please be seated. 
241 

1The prepared statement of Mr. Bellina appears in the Appendix on page 284. 

Our first witness is Matthew Bellina. Mr. Bellina is a former 

U.S. Navy aviator, retiring at the rank of Lieutenant Commander. 

He received his commission in 2005 after graduating from Virginia 

Polytechnic Institute and State University (Virginia Tech). In April 

2014, he was diagnosed with ALS. He is a husband and a father 

of two boys, with another on the way. Mr. Bellina. 

Senator CARPER. And, if any of your family members are here 

and you would like to introduce them, please do. And, that is for 

all of the witnesses. 

TESTIMONY OF MATTHEW BELLINA,1 LIEUTENANT 

COMMANDER, U.S. NAVY (RETIRED) 

Mr. BELLINA. Thank you so much, Senators. And, thank you for 

having me. I would like to introduce my family. My kids are the 

boys that were making noise while you were speaking—and I 

apologize. 

Senator CARPER. I would have been afraid, when my boys were 

their ages, to have brought them to a hearing like this. [Laughter.] 

Mr. BELLINA. Yes, it was risky, but I did not want them to miss 

it. 

Senator CARPER. They are doing great. 

Mr. BELLINA. It is Caitlin, JP, and Kip siting back there. 

Senator CARPER. Would you all raise your hands? Would you 

raise your hands, please, kids? There you go. 

Mr. BELLINA. And there is an unnamed baby on the way as well. 

Senator CARPER. That is good. 

Chairman JOHNSON. Go ahead, Matt. 

Mr. BELLINA. Thank you, Senator. 

So, last night, when I was laying in bed, I was 

uncharacteristically nervous about this. Senator Carper, as somebody who has worked in naval aviation, you can understand. We 

are not usually nervous about things. But, I felt a great burden to 

speak on behalf of all terminal patients. How do you do that? And, 

then, a kind of calm washed over me because I realized that this 

is not a class or a group of people that we can all lump together. 

We are talking about individuals, and they have individual needs, 

individual hopes, and individual dreams. And, I do not have the 

right to speak on their behalf or to make decisions for them. And, 

neither does anybody else in this room. 

I think the first thing I want to clarify is that I am proud of the 

FDA’s ‘‘Gold Standard.’’ I am proud of what the FDA does. I am 

proud that American medicine is the best in the world. And, I 

would never, ever want them to relax those standards for any reason. I think that that is an important distinction. We are not trying 

to undermine the FDA. 

This is a situation where we are asking for a very specific carveout for a very small exception that does not necessarily—well, it 

does not cost us any money. I am not asking to build a wall. I am 

talking about making an exception for people that really need it. 

I am so happy, Senator Carper, that you mentioned compassionate use. I would like to commend the FDA. I think that they 

have done an excellent job of doing everything, within their regu-
242 

latory power, to approve things. But, unfortunately, the data has 

a bit of a sample bias. I think there were 1,000 approved this year. 

There were 12,000 in France, if that gives you any idea. There 

were not that many people applying, and I think that it has a lot 

to do with the reporting requirement. No pharmaceutical company 

in their right mind would give me a drug compassionately, because, 

if I have an adverse event—which, I am an ALS patient, let us face 

it, I probably will—they have to report that to the FDA, and it is 

going to jeopardize their standing and their trial. 

We are dealing, in this case, with heterogeneous diseases. There 

is not a single cause. ALS is a perfect example. There are, I think, 

39 known genetic mutations for ALS. That only makes up 10 percent of the overall cases. The other 90 percent are sporadic—and 

they are largely veterans. We do not know why. People who have 

worked in aviation are about eight times as likely to get ALS. 

So, when you run an FDA trial, as we are doing them now, you 

are throwing, at best, 400 people into a room together, giving them 

a small molecule, and hoping to get a result. Well, the data is kind 

of garbage in, garbage out. We are not getting good data. And, we 

need to move toward personalized medicine, in these cases. 

I feel that, ‘‘Right to Try’’ may not be, exactly, the end goal, but 

it is a first down. We are moving the marker toward doctors, patients, and pharmaceuticals being able to look at patients as individual people. And, I think that is a really important step. It is an 

ideological thing. I have heard the argument that we will risk side 

effects. But, as you can tell, I am struggling here. At some point 

in the near future, I am going to suffocate under the weight of my 

chest. So, what difference, at this point, does it make for me to 

have a side effect? 

And so, I think that, when you are talking about toenail fungus 

or psoriasis—yes, we need to be concerned about that. But, where 

I am sitting—it is a totally different story. 

The other thing some bioethicists have talked about is, ‘‘false 

hope.’’ Do we want to give terminal patients ‘‘false hope? ’’ Well, I 

do not really think there is such a thing, because right now we 

have no hope, so it is either hope or no hope. This bill, it does not 

do everything, but it moves us in the direction of having a little bit 

of hope. And, I think that it is very consistent with what the FDA 

is doing right now. I commend them. The Sarepta approval was 

fantastic. But, we need to open things up for the market to be able 

to kind of correct for itself and allow the pharmaceutical companies 

to not have to worry about negative action against them if they are 

trying to do something good. 

Chairman JOHNSON. Thank you, Matt. 

Mr. BELLINA. Thank you. 

Chairman JOHNSON. Our next witness is Assemblyman Ian 

Calderon. Assemblyman Calderon is the majority leader in the 

California State Assembly, where he was first elected to represent 

the 57th Assembly District in November 2012. 

He serves as the Chair of the Select Committee on Youth and 

California’s Future and Co-Chair of the Legislative Technology and 

Innovation Caucus. He has previously worked at Hurley International and is a field representative for the California Assembly. 

Assemblyman Calderon. 
243 

1The prepared statement of Mr. Calderon appears in the Appendix on page 286. 

TESTIMONY OF THE HONORABLE IAN C. CALDERON,1

MAJORITY LEADER, STATE ASSEMBLY, STATE OF CALIFORNIA 

Mr. CALDERON. Thank you, Chairman Johnson, Ranking Member 

Carper, and Members of the Committee for inviting me here today. 

I am honored to testify before you on the ‘‘Right to Try’’ for terminally ill patients. 

As Majority Leader of the California State Assembly, I am fortunate to work on a variety of public policy issues every year. This 

year, alone, I have sent bills to the Governor dealing with issues 

ranging from ensuring that financial literacy is part of the high 

school curriculum to setting minimum fines for piracy violations. 

While each bill I work on is a piece of policy I believe in strongly, 

my work on ‘‘Right-to-Try’’ legislation, over the last 2 years, has 

truly given me purpose as an elected official. The fight to allow terminally ill patients to seek investigational drugs and treatments 

not yet approved by the FDA is something I am immensely proud 

to be a part of in California. And, I thank you for giving me the 

opportunity to talk about it today. 

In January 2015, many of the policy conversations in California 

centered around ‘‘Death with Dignity.’’ If you recall, this was mere 

months after Brittany Maynard, the young woman diagnosed with 

brain cancer, had moved from California to Oregon in order to utilize Oregon’s ‘‘Death-with-Dignity’’ law. While researching Oregon’s 

law and its possible application in California, it struck me that this 

conversation needed to include policy prescriptions to make it easier for these terminally ill patients to fight to save or extend their 

lives. It was then that I came across the ‘‘Right-to-Try’’ movement, 

and subsequently introduced Assembly Bill 159. For me, ‘‘Right to 

Try’’ was a logical companion to ‘‘Death with Dignity.’’ I never saw 

the two issues as incompatible. I did not want to limit the options 

for those diagnosed with a terminal illness only to death—albeit a 

more controlled one. I felt strongly that, if we were going to pass 

‘‘Death with Dignity,’’ and thus make it easier for terminally ill patients to die in California, that we should also make it easier for 

these terminally ill patients to fight to live, by giving them access 

to potentially lifesaving drugs and treatments that have been 

deemed safe—but are not yet approved by the FDA. 

As the first iteration of California’s ‘‘Right-to-Try’’ legislation 

made its way through the legislative process, I had the privilege of 

meeting David Huntley. David was a professor emeritus at San 

Diego State University, an accomplished Ironman triathlete, and 

an, obviously, loved husband and father. David was also diagnosed 

with ALS, more commonly known as Lou Gehrig’s disease. It is a 

death sentence given our current lack of understanding of the disease—but there are ways to combat the speed at which it progresses and the pain that it causes. Shortly after his diagnosis, 

David learned that there was a promising new drug called GM604 

that was still in the clinical trial process at the FDA and, thus, had 

not yet been approved. He sought access to this drug, but was denied. So, David spent the latter part of his life fighting to give patients, like himself, a chance. David agreed to fly up to Sacramento 

in April of last year to testify with me before the California Assem-
244 

bly Health Committee. This was the first committee hearing on the 

‘‘Right to Try’’ in California. David’s testimony and clear understanding of the pitfalls of the current experimental drug access paradigm were instrumental in getting us past the first legislative 

hurdle. 

It was evident that David was in a tremendous amount of pain— 

yet he was determined that he be there for the ‘‘Right-to-Try’’ legislation and that it pass in his home State. Just 3 months after testifying, on July 4, 2015, David Huntley succumbed to ALS and 

passed away. He came to Sacramento to testify for a measure he 

knew would be too late to help himself, but that would ensure that 

future terminally ill patients have the access to potentially lifesaving medication that he had been denied. That kind of selflessness is rare—and I will never forget his dedication. 

With David’s help, ‘‘Right to Try’’ passed the Assembly Health 

Committee. But, it still faced intense scrutiny from five more committees in the State Assembly and the State Senate. Though this 

was only last year, it was early in the ‘‘Right-to-Try’’ movement. 

The bill went through a rigorous public hearing process, where we 

sought to improve upon the ‘‘Right-to-Try’’ legislation that had been 

introduced in other States. Each committee, in concert with the 

myriad of stakeholder groups—and in deference to concerns that 

felt unique to California—included amendments to the legislation. 

Throughout the Committee process, we worked on—and eventually 

added—several amendments to alleviate concerns about having 

proper oversight patient protections. We added Institutional Review Board (IRB) oversight of a physician’s recommendation, in 

order to ensure that patients are fully aware of the potential side 

effects of any investigational drug they may consume. We also 

added the requirement that a consulting physician confirm the primary physician’s diagnosis that the patient is terminally ill as well 

as inserted reporting requirements into the California Department 

of Public Health (CDPH) to further increase oversight. And, similar 

to the difference I see in Senator Johnson’s ‘‘Right-to-Try’’ bill 

versus the House’s version, we clarified that the legislation would 

not create a private cause of action against the prescribing physician or drug manufacturer—and this was instrumental in removing 

the opposition of the California Medical Association (CMA). 

While we were not able to completely remove all opposition to 

California’s ‘‘Right-to-Try’’ bill, through the public hearing process, 

we did work to address many of these concerns, without compromising the strong intent of the bill. When my ‘‘Right-to-Try’’ bill 

reached the Governor’s desk last year, I was satisfied that, due to 

its strong patient protections and robust oversight requirements, it 

was one of the most comprehensive ‘‘Right-to-Try’’ pieces of legislation in the country. 

The Governor ultimately vetoed the bill. And, in his message, he 

acknowledged that the FDA was in the process of streamlining its 

Expanded Access application and wanted to grant the agency the 

time to do so—with the hope that this new application would make 

the process unnecessary. Thirty one other States have passed 

‘‘Right-to-Try’’ legislation. I am happy to have been a part of the 

impetus that spurred the FDA to streamline the application. However, these new regulations—announced in June of this year—only 
245 

deal with streamlining the physician’s portion of the application. 

This is an improvement, but the process does nothing to shorten 

the manufacturer’s portion and the data required by the application or to reduce the 30 days the FDA has to decide. A thousand 

people are approved each year by the FDA to get access to these 

drugs, but considering the fact that 564,000 Americans are expected to die from cancer, alone, this year, the small number of 

people navigating the FDA’s Expanded Use program speaks to the 

program’s failure to actually help terminally ill patients obtain access to lifesaving treatment. These patients do not have the luxury 

to wait for an onerous, bureaucratic process. These are the reasons 

why ‘‘Right-to-Try’’ legislation is so important, and, in the midst of 

a battle with a life-threatening illness, it is much easier for a patient to deal with their own doctor rather than a large and impersonal government agency. 

At the beginning of this year, I reintroduced the bill in California. Fortunately, with all of the protections we added last year, 

it sailed through the legislature. It now sits on the Governor’s desk, 

where I am hopeful it merits a signature, adding California as the 

32nd State to enact this legislation. 

Members, I thank you for giving me the opportunity to share my 

effort to bring ‘‘Right to Try’’ to California. I applaud the effort on 

the Federal level to do the same nationwide. I hope the Federal 

Government does not stop there. We need Federal legislation that 

expedites the FDA’s drug approval process. It should not take, in 

today’s technology age, 10 to 15 years to approve a new drug that 

will produce lifesaving treatments. In the meantime, I commend 

the Federal effort to encourage the States to essentially adopt 

methods to work around the FDA. 

‘‘Right to Try,’’ at its core, is simple, and it speaks to a very basic 

human right. If your parent, your child, or even you are faced with 

a terminal illness, there should be a process in place for you to 

seek potentially lifesaving treatments—and the government should 

not impede that. This bill received unanimous bipartisan support 

in the California State Assembly—all Democrats and all Republicans—and it is extremely important to pass it on the Federal 

level because it gives us, as a State, the opportunity to have these 

laws on the books while also, at the same time, freeing up the drug 

manufacturers, allowing them to give the drug to these terminally 

ill patients. 

Members, thank you for your time. 

Chairman JOHNSON. Thank you, Assemblyman Calderon. 

Our next witness is State Representative Jim Neely. Representative Neely represents the 8th State House District in the Missouri 

House of Representatives. He was first elected in November 2012. 

He is also a physician at Cameron Region Medical Center and a 

veteran of the United States Army. He also previously served for 

over a decade on the Cameron School Board. Representative Neely. 
246 

1The prepared statement of Mr. Neely appears in the Appendix on page 292. 

TESTIMONY OF THE HONORABLE JIM NEELY, D.O.,1 MEMBER, 

HOUSE OF REPRESENTATIVES, STATE OF MISSOURI 

Dr. NEELY. Good morning. Thank you. Mr. Chairman and Members of the Committee, again, my name is Jim Neely. I am a physician, State representative, and, more importantly, a dad. I want to 

go on record in support of S. 2912 because terminally ill patients 

do not have time to wait for the FDA to improve investigational 

treatments. 

I have been practicing medicine for over 30 years. Over that 

time, I have seen patients with medical conditions and issues of life 

that have been very challenging to deal with, from multiple 

myeloma, multiple sclerosis (MS), ALS, to acquired immunodeficiency syndrome (AIDS). 

In 1985, I had my first AIDS patient. I was practicing medicine 

in Florida at the time. My first AIDS patient, he was debilitated, 

frail. He was hopeless. A year later, he died. He was not eligible 

for any clinical trials. They did not approve the first antiretroviral 

(ARV) agent until a year later. 

Throughout my medical career, I have been troubled by laws that 

restrict suffering patients’ access to investigational treatment. As a 

physician, my practice is guided by evidence. I understand the importance of our clinical trial system. However, terminally ill patients deserve the option to try investigational treatments after 

they have exhausted all approved treatment options and they are 

no longer eligible for clinical trials. 

As I began considering the issues as a State legislator, my 

daughter Kristina was diagnosed with Stage IV colon cancer. She 

had four children at the time and was pregnant with the fifth, 

which severely limited her eligibility for clinical trials. From a research perspective, I understand the importance of studying uniform groups of patients, but there has to be room for compassion 

for patients like our daughter. 

Before she passed away, just last year, she was adamant, I 

quote, treatments ‘‘should not be up to somebody that has no involvement in my care.’’ I believe this bill goes a long way to providing more options for terminally ill patients and their physicians. 

A friend of mine, Ross Nichols, testified on our bill, in Missouri, 

on ‘‘Right to Try.’’ It passed unanimously out of the Senate and out 

of our House. It passed 152–1. The one who voted no never votes 

yes. This gentleman, Ross, he had glioblastoma (GBM), the most 

aggressive—the most common brain tumor. Ross knew that the experimental treatments he was likely to receive would not save his 

life. But he still enrolled in clinical trials. He explained, ‘‘My number one job right now is being a dad. I will do whatever I can do 

to extend that.’’ Ross told the committee that he was testifying for 

the bill because he wanted people in Missouri to have access to the 

same treatments that were available to him at the research institutions that he could afford to travel to. He was right. 

Many people fighting for their life cannot afford to spend what 

could be their final months traveling across the country in order to 

receive investigational treatments. I am glad Ross was able to travel and receive treatments that gave him hope, but he should not 
247 

1The prepared statement of Mr. Garr appears in the Appendix on page 296. 

have had to travel. Ross passed away in February 2015. I am glad 

his hope for other patients lives on with this bill. 

Rick Suozzi, father of the late Kim Suozzi, also came to testify 

in support of our ‘‘Right-to-Try’’ bill in Missouri. His daughter was 

diagnosed with glioblastoma at the age of 21 in her final semester 

at Truman State University. Kim knew her diagnosis was a death 

sentence, but she went to extraordinary lengths for a small chance 

to survive. She traveled to the top-notch cancer institutes like 

Dana Farber Cancer Institute, UCLA, Duke, the University of 

Texas MD Anderson Cancer Center (MD Anderson). Kim enrolled 

in three trials in the last 6 months of her life. She was no longer 

eligible for clinical trials. She lied to research doctors about her 

treatment history in order to make herself eligible. Can any of us 

blame her? 

My time is up. I thank you for giving me the opportunity. I believe government should create opportunities for people to care for 

each other. This bill knocks down some of those barriers. I appreciate the opportunity to be here today. It is an honor. Thank you. 

This is a bill for people. Thank you. 

Chairman JOHNSON. Thank you, Dr. Neely. We are so sorry for 

your loss, but thank you for your testimony. 

Our next witness is Richard Garr. Mr. Garr is the co-founder of 

Neuralstem, Inc., which develops therapies involving brain and spinal cord stem cells, including a treatment for ALS currently in clinical trials. He was previously president and Chief Executive Officer 

(CEO) of the company. Prior to Neuralstem, he was an attorney at 

Beli, Weil, & Jacobs, the B&G Companies, and the Circle Management Companies. He is also the founder of the First Star Foundation, The Starlight Foundation Mid-Atlantic chapter, and a past 

honorary chairman of the Brain Tumor Society. Mr. Garr. 

TESTIMONY OF RICHARD GARR,1 FORMER PRESIDENT AND 

CHIEF EXECUTIVE OFFICER, NEURALSTEM, INC. 

Mr. GARR. Thank you. I would like to thank the Committee for 

this opportunity to testify in support of this Act. 

As president and CEO of a biopharmaceutical company developing treatments for currently incurable diseases, as a member of 

the advisory board that helped craft the model ‘‘Right-to-Try’’ act 

which has been making its way through the States, and as the father of a son diagnosed with a brain tumor, I have been involved 

in the scientific, FDA regulatory, business, legislative, and patient 

advocacy arenas germane to this issue for over two decades. 

S. 2912 is a good bill that will provide hope and comfort to many 

patients diagnosed with fatal diseases and it will accelerate the effort to find cures for currently incurable diseases. 

There are issues—and I would like to spend my limited time 

here, today, talking about them. 

An issue we hear is that this is going to foist unsafe medicines 

on an unsuspecting public. Nothing could be further from the truth. 

This bill relies on FDA oversight. As you know, any drug that can 

be administered under this has to have gone through an FDA 

Phase I trial and has to continue to be in the FDA queue, which 
248 

is a very important point. So, if a company pulls a drug out of the 

FDA process for any reason—safety or otherwise—it is no longer eligible to be administered under this Act. 

I also think it needs to be pointed out that, companies do not develop drugs for incurable diseases without spending an enormous 

amount of time and money. This is not an undertaking you go into 

lightly. At Neuralstem, it took us at least $50 million and 10 years 

just to get into our first trial for ALS. So, in addition to the FDA 

safety data, which you get from the trials and which are required 

for a doctor to administer this drug, there is always a large body 

of pre-clinical safety data—such as animal data, in vitro, and in 

vivo data. And so, there is a lot of safety data for these drugs. 

I would also—as other people have said here—like to debunk the 

myth that this is somehow an anti-FDA bill. Nothing could be further from the truth. The heart of this bill is the safety net that continuing FDA oversight provides—an oversight, as everyone has 

said, that is universally acknowledged as the gold standard for the 

world. And, I would point out here that even proponents of the 

‘‘Right-to-Try’’ movement, such as the Goldwater Institute, who 

probably believe that ‘‘Right to Try’’ is based on a constitutional 

principle and disagree with the idea of Federal preemption, have 

insisted on the FDA oversight principle of safety in all of the 31 

Acts so far that have gotten through the States. This is not an antiFDA bill. 

I would like to address your issue, Senator Carper, briefly. We 

did two trials for ALS. We will be starting a third, hopefully, in the 

not too distant future—but, probably, in Japan for regulatory reasons. So, we treated 40 patients—15 in the first trial. It took us 

18 months to transplant those—to do those 15 surgeries. We had 

at least—and I am just thinking of my own personal emails at 

night—600 people who asked if they could have it on a compassionate use basis. It cost us $150,000 per patient—and that is without charging anything for ourselves—for each patient in that trial. 

So, the reason that the FDA’s compassionate use vehicle, or tool, 

is not applicable is that is a tool, but it is a tool for a very specific 

use—and maybe about 1,000 people a year can do it. 

In a case like ours—and I would tell you that all of the products 

that are being developed for incurable diseases are not cheap pills. 

They are all cell therapy or gene cell, monoclonal antibodies. It is 

very expensive technology. And, the fact is we could not do any 

compassionate use—we could not possibly meet the need. We did 

not have the money and we did not have the time or the resources. 

Maybe GlaxoSmithKline can do it for a cancer drug. But, they are 

not developing these drugs. The biotechnology industry is developing these experimental medicines. And so, another part of this 

that has to be addressed—and the States will have to do it—is you 

have to let the companies charge for this—and you cannot do that 

under your existing compassionate use guidelines with the FDA. 

There are very strict limits on cost. And, actual cost for our product—for me to send our cell guy up to Charles River Labs in Pennsylvania, to follow the cells, to do what we do, and to ship them 

to the surgeon has nothing to do with the $50 million that it costs 

us to get to that point. And so, there is something that just does 

not work there. 
249 

1The prepared statement of Mr. McFayden appears in the Appendix on page 299. 

I see that I am running out of time, so I do want to mention one 

last thing, and that is—as you are hearing from everybody here, 

this is a ‘‘Right-to-Try’’ Act, not a ‘‘Right-to-Cure’’ Act. And, what 

the doctors who deal with the patients and the caregivers will tell 

you, almost across the board in all of these diseases—not just 

ALS—is that people with fatal diagnoses—and this bill only applies 

to drugs for fatal diseases. People with fatal diagnoses have a sense 

of hopelessness and their caregivers do also. And, many of them 

feel that they have lost control of their lives. They want to go down 

fighting. They want to help research. No one who gets an experimental drug—even if we are all hoping that it can work—we do not 

develop drugs that we do not think are going to work. But, the fact 

is, over 90 percent of them fail—even those that get to late-stage 

trials. 

So, the industry is meticulous in educating patients about the realities of what is going to happen. And, they still want to go 

through it. Yes, they have hope and they want to help the research—and this will accelerate research. And so, I think it is also 

an extremely important part of these ‘‘Right-to-Try’’ Acts that you 

give people back some control of their lives in a place where science 

is telling them they have lost control and that is why they have 

this fatal diagnosis. 

Thank you for the time. 

Chairman JOHNSON. Thank you, Mr. Garr. 

Our final witness is Andrew McFadyen. Mr. McFadyen is the executive director of The Isaac Foundation, a nonprofit focused on 

funding and supporting research into finding a cure for 

Mucopolysaccharidoses (MPS), a rare and progressive disease affecting his eldest son. As part of his work, he is a member of the 

New York University (NYU) Langone Medical Center Working 

Group on Compassionate Use and Pre-Approval Access. He is also 

an eighth grade teacher in Kingston, Ontario and a guest lecturer 

at Queen’s University Faculty of Education. Mr. McFadyen. 

TESTIMONY OF ANDREW MCFADYEN,1 EXECUTIVE DIRECTOR, 

THE ISAAC FOUNDATION 

Mr. MCFADYEN. Thank you. And, I want to actually begin by just 

welcoming my kids, Isaac and Gabriel. They are my inspiration in 

all that I do. And, I wanted to use a little bit of my time as well 

to recognize you, Matthew. Your story is incredibly heartbreaking. 

Your family is just beautiful. And, you are an inspiration to me and 

I am glad that you are here. 

So, good morning. I am the executive director of The Isaac Foundation, an organization based in Canada that is dedicated to providing advisory and support to patients dealing with a wide range 

of disorders and needing access to rare disease treatments. Our 

work pushes international boundaries, with the bulk of our efforts 

taking place in Canada and the United States. I am also a member 

of the NYU Working Group on Compassionate Use and Pre-Approval Access, where we are making a concerted effort to improve 

and address the issues around access to experimental medications. 
250 

I am very proud to say that at The Isaac Foundation we have 

never, ever been unsuccessful in gaining access to rare disease 

treatments for children in Canada. And, our work, directly, with 

pharmaceutical companies here in the United States is helping 

countless patients see similar results as well. 

Now, as I stated, my organization is incredibly dear to me because it is named after my son—my hero and the bravest person 

I know—Isaac McFadyen, who is here behind me today and who 

suffers from MPS Type VI. 

When Isaac was diagnosed, we were told that he was going to 

live a life of pain and suffering. Every bone, tissue, organ, and 

muscle in his body—with the exception of his brain—would be ravaged by his disease until he eventually succumbed to the condition—probably in his early to late teens. 

For 10 years, he has battled—we have battled together—to stave 

off the inevitable. And, we have been lucky. In 2006, we were able 

to gain a new life-prolonging treatment—one that was approved 

here by the FDA, but not by Health Canada—to fight his disease. 

Isaac is now 12 years old—and the 12 that we see today is very 

different than the 12 we were told to prepare for. 

So, I fully understand the world that our families are living in 

and I understand the unbearable burden that a terminal diagnosis 

brings to a family. I understand because I live each and every day 

staring down the mortality of my son. I understand because I have 

walked this lonely road searching for hope when all seemed lost. 

I have been there—and I am still there each and every day as I 

continue to work tirelessly to find a cure for Isaac before the clock 

runs out. 

Now, as I said, Isaac is one of the lucky ones. Unfortunately, little Jack Fowler in the picture here is not. Jack was diagnosed with 

a version of MPS similar to the type that Isaac has—except Jack 

has the tragic misfortune of having his disease attack his brain. 

The disease will progress rapidly and steal everything that makes 

Jack Fowler Jack Fowler—his mobility, his words, his thoughts— 

his everything—before finally taking Jack Fowler away from us. 

Now, there is a drug that can prevent this from happening, but 

Jack barely missed out on qualifying for the clinical trial and he 

was not able to obtain the drug under the FDA’s expanded access 

program because, despite his physician, the hospital, the hospital 

review board, and the FDA all supporting his case, Shire Pharmaceuticals blocked access to the drug. Today, hope is all but lost for 

his parents as they watch their son slip away. 

But, how can hope be lost for Jack Fowler when he lives in a 

State where ‘‘Right-to-Try’’ legislation is in place? The Goldwater 

Institute has done a marvelous job of promoting ‘‘Right-to-Try’’ 

laws as being the last chance for people to extend their lives. Very 

pointedly, they claim that ‘‘Right-to-Try’’ legislation ‘‘restores lifesaving hope back to those who have lost it.’’ This utopian vision of 

access to medications for millions of Americans who need them is 

laudable. However, the cruel reality with ‘‘Right-to-Try’’ laws is 

that it will not grant patients the immediate access to the treatments they desperately need—the and it never has. 

Looking past the myths that ‘‘Right-to-Try’’ proponents state ad 

nauseam and looking past this legislation’s potential to create an 
251 

unequal access to medication, the simple fact is that this legislation, crafted to give people like Jack Fowler his fair shot of simply 

being alive, does not work. Although over 183 million Americans, 

including Jack Fowler, are currently living within the boundaries 

governed by ‘‘Right-to-Try’’ laws, providing them with, as the Goldwater Institute claims, immediate access to the medical treatments 

they need, there continues to be no concrete evidence of a patient 

ever receiving a life-saving medication under ‘‘Right-to-Try’’ legislation that they otherwise would not have received under the FDA’s 

expanded access program. 

In truth, ‘‘Right to Try’’ is a misnomer and provides nothing to 

patients in need, except a misguided belief that help has arrived. 

A more apt title would be ‘‘Right to Ask’’ because this is the only 

entitled right the legislation actually gives patients. 

There are ways forward. Over the past few months, companies 

like Janssen and BioMarin are crafting new approaches while 

working within existing FDA programs and guidelines to expeditiously and fairly provide access to those in need—and it is working. 

So, recognizing that we are all here to work toward the same 

outcome, I hope that we can move now and that we can keep moving until everyone in this room and everyone throughout the country can look the parents of Jack Fowler in the eyes and tell them 

that help is on the way, that help is here, and that Jack will get 

to realize his simple dream of being alive. 

Thank you. 

Chairman JOHNSON. Thank you, Mr. McFadyen. And welcome, 

Isaac. 

I have been told that Frank Mongiello is in the audience and he 

would like to make a brief statement. If we can assist Frank, get 

him up to a microphone. We have some staff coming down. 

TESTIMONY OF ERIC AND FRANK MONGIELLO 

Mr. ERIC MONGIELLO. So, first I would like to start off by reading 

a quote from Mahatma Gandhi, and it—— 

Chairman JOHNSON. And you are Frank’s son? Can you just introduce yourself quickly? 

Mr. ERIC MONGIELLO. I am Eric Mongiello. This is my dad right 

here, Frank Mongiello. 

So, starting with this quote: ‘‘You may never know what results 

come of your actions, but if you do nothing, there will be no results.’’ 

Basically, what is that meaning? We do not have the luxury of 

time to wait around until this bill gets passed. Every day is another day off my dad’s life, and others with terminal illnesses. Me, 

personally, I do not want to have to grow up without a father. I 

do not want my little brother and my siblings to have to grow up 

without him. And, with the ‘‘Right to Try,’’ this will give us hope. 

We have no hope right now. And, this is very important to me because, as long as we have a fighting chance, then I know whatever 

happens, whether it helps or not, that at least we tried, and at 

least we did something instead of sitting by the side and waiting 

for the inevitable. Thank you. 

Chairman JOHNSON. Thank you. Frank. 
252 

Mr. FRANK MONGIELLO. Thank you very much for having this 

hearing. 

My ALS is progressing every day [unclear]. We do not have the 

luxury of time. 

All we are asking for here is a basic inalienable right to live 

every [unclear]. I do not want to die, but I want to be able to fight 

for my life, and if that means taking a drug that might not be proven by the FDA, I am OK with that. 

It is my life. I should have the right to fight for it. Thank you. 

Chairman JOHNSON. Thank you, Frank. 

Frank made a statement when we had a press conference on 

this. And, Frank has a beautiful family and he is just asking for 

that right to hope. 

Mr. Garr, I will start with the questioning. Can you respond a 

little bit to Mr. McFadyen? Why would Shire block access to—can 

you just kind of explain that? 

Mr. GARR. I am not from Shire, so I will not speak for them. 

Chairman JOHNSON. I understand, but I mean, can you—— 

Mr. GARR. In general, sure, and I would like to address this 

claim, which is that nobody has been treated with ‘‘Right to Try.’’ 

The reason no one has been treated with ‘‘Right to Try’’ is that this 

bill has not passed, right? As you put your industry hat on, all of 

the issues that have to be addressed, in terms of whether the FDA 

can use negative information to withhold your approval in the regular approval process—that is the reason, right? This bill, specifically, prohibits the FDA from doing that. When you design a trial, 

you eliminate as much of the variables as possible to match your 

evidence—your pre-clinical evidence—and you create an experiment. Correct? And then, when you go to ‘‘Right to Try’’ or compassionate use, you start treating people, as the doctor said, that are 

outside of that. 

And so, it is very difficult, as a company, after you have just 

spent 10 years and $1 billion, or whatever it is Shire spent on their 

drug, to get to a point and then say, ‘‘OK, we know that if this goes 

into patients that do not meet the inclusion criteria, there could be 

problems.’’ So, they have an obligation to their shareholders to get 

their drug approved. That is probably what they told themselves. 

I do not think I agree with it, but that is what the obligation is. 

And, no company, I will tell you—and he confirmed that, right? No 

company will feel comfortable going through this. When you go 

through the compassionate use process with the FDA, that limited 

tool, you have some protection. Under the current State ‘‘Right-toTry’’ Acts, you have none. 

Chairman JOHNSON. And, that is basically the reason. You have 

the 31 States that have passed this, but because you have no protections at the Federal level, anybody like Dr. Delpassand is taking 

a huge risk. That is why I call Dr. Delpassand a real hero. He is 

taking an enormous risk with his career treating these patients 

and giving them hope. So, we really need the Federal law in order 

for the State laws to actually kick in. And, that is really, I think, 

what the strategy was—to show the support for ‘‘Right to Try’’ in 

the States— but until the Federal Government acts, the State laws 

have not been effective. 

Mr. GARR. Absolutely. 
253 

Chairman JOHNSON. Assemblyman Calderon, first of all, what 

party affiliation are you? 

Mr. CALDERON. I am a Democrat. 

Chairman JOHNSON. And, again, this had very strong bipartisan 

support. You made the statement—and this is in terms of the simplicity of what we are asking for here—patients have the right to 

die in certain jurisdictions, and yet they do not have the ‘‘Right to 

Try.’’ Where is the logic in that? 

Mr. CALDERON. I do not know. That is why I felt, once I got the 

bill to the Governor’s desk, that it would merit a signature—because of the State at the time dealing with the ‘‘Death-with-Dignity’’ law. However, the Governor vetoed and we have been working with his office and we are hopeful that we will get a signature 

this year. 

Chairman JOHNSON. Can somebody explain, again, the statistics 

of 99 percent of expanded use being approved—1,000 patients 

versus how many would be, potentially, looking at this? Matt, I 

see—— 

Mr. BELLINA. Senator Johnson, if I could weigh in on that. So, 

before you apply for compassionate use, as a terminal patient, you 

go and talk to your doctor and say, ‘‘What do you think about this 

thing?’’ And, they look at you as a person, it is between you and 

your doctor—it is your body. And, they say, ‘‘Yes, I think that could 

help you,’’ or, ‘‘No, there is not enough data,’’ or whatever. 

If they think it is a good idea, the next thing you are going to 

do is call the company, and you are going to say, ‘‘Hey, you are in 

a Phase IIb trial with this drug, and I want to try it.’’ And, I am 

going to tell you, from personal experience, about 50 times, you are 

not going to get a response. 

Chairman JOHNSON. So, you personally, have made those calls? 

Mr. BELLINA. I have made those calls, personally. And, I cannot 

get into an FDA trial because I do not meet exclusion criteria. I 

have had the disease for too long. So, there is literally no way for 

me to get these drugs. As Mr. Garr said, I mean, they are not going 

to risk giving me a drug and risk me having an adverse event. 

They would have to report that to the FDA. They have already 

spent—who knows—maybe $100 million at this point. 

Chairman JOHNSON. Does anybody have any kind of statistic regarding , how many Matts are out there, that have made those 50 

calls, in comparison to the 1,000 successful applications of expanded use or expanded access? 

Mr. BELLINA. Senator, I think that is, again, something we will 

never know simply because it never gets to the government at that 

point. You are talking about a gmail account to a gmail account. 

This is not under any kind of regulation. These are just people 

reaching out to people in these companies—and there is no way to 

quantify that. 

Chairman JOHNSON. Yes. 

Mr. CALDERON. Senator, if I may, I was elected to the California 

State Assembly when I was 27 years old. I am 30 now. I am the 

youngest majority leader in the history of the State of California. 

But, I am also a Millennial, and part of my generation—everybody 

is trying to say, ‘‘Well, how do we get them engaged? How do we 

get them to care about our political process?’’ A lot of it is just our 
254 

perception that government just has this inability to reach these 

common sense ideas. Why would you not allow someone who is terminally ill the ability to try and fight to save their own life? It is 

beyond logic to me. 

Chairman JOHNSON. So, having fought this successfully legislatively, what was the primary argument against—I mean, in the 

end, you knocked down all of those walls because you passed this 

almost unanimously, correct? 

Mr. CALDERON. Absolutely. 

Chairman JOHNSON. Just one person voted no. 

Mr. CALDERON. And, in terms of the opposition, the problem was 

more, a question of whether there was liability. All that my bill 

did, really, was give people the ability to try and ask for the drug. 

That is all the intent of the original bill was. But, given the opposition, we added all of these patient protections and oversight. By the 

time the bill got to the Governor, the reason why the Governor vetoed it is because, within the expanded access, the FDA was working on an expedited way to get access to those drugs. 

But, look, let us be honest. If I had a terminal illness, I would 

want to live. I am probably not going to want to deal with 

the FDA, because how do you figure that out? I do not even know— 

I am authoring the bill in California. I do not even know where I 

would go. I guess I would just go online and google how I would 

even apply for the program. But, contrast that with the State having a law on the books where you can just talk to your own doctor 

and say, ‘‘Hey, Doc, I am terminally ill. I want to fight to live. I 

do not care what it takes. Give me anything that is going to allow 

me to stay on this Earth longer.’’ Or, if it is for my kids or a parent. 

Chairman JOHNSON. But, you were able to overcome the objections, and our bill also overcomes those same objections, basically? 

Mr. CALDERON. Absolutely. 

Chairman JOHNSON. Just very quickly, Dr. Neely—a similar situation. What objections—why did anybody oppose this in Missouri? 

Mr. NEELY. In the State of Missouri, nobody had any issues. Everybody was all on board. It was about taking care of people. I 

think, at our level, it is all about taking care of people. And, I think 

that is what we have done. 

I might add we had—one of my staff physicians at Cameron 

came down with ALS in 2014 right after Missouri passed their 

‘‘Right-to-Try’’ legislation, and I was telling him about it, and the 

trials that were going on for ALS in the San Francisco area. Again, 

he was in his early 70s. He had been practicing medicine for 40 

years. He did not want to have to deal with the government. 

Chairman JOHNSON. OK. Senator Carper, are you ready? 

Senator CARPER. I am. 

Chairman JOHNSON. Senator Carper. 

Senator CARPER. Thank you again. Matt, gosh, about 15 years 

ago, my brother-in-law was diagnosed with ALS, and so, we lived 

what you are going through. 

My mother passed away about 8 years ago—Alzheimer’s. Her 

mother, her grandmother, her sister. My guess is everyone on this 

panel could tell a story. Everyone. 
255 

Andrew, let me ask you a question. I do not know how familiar 

you are with the changes that have been made in the approval 

process at the FDA to expedite access to experimental treatments. 

But, my understanding is that there had been a lot of criticism, in 

the past, of the FDA. The FDA has been responsive to those criticisms. Could you just walk us through some of that? And, I will 

ask Dr. Lurie the same question later. But, are you familiar with 

that? 

Mr. MCFADYEN. Yes, I am, actually. I understand that they have 

made changes. They released guidance, in June, talking about 

issues that could take place—adverse events and how impact clinical trials. At the same time, they updated their application form. 

It has been said—I have heard it often—that it takes 100 hours to 

fill out this form—and that is just not the case. It takes 100 hours 

for the company, before they apply to the FDA, to fill out those 

forms. The old form, it did take a few hours to do. We went 

through it with Jack Fowler. We looked at it long and hard with 

Jack Fowler. I did it, myself, and it did not take that long. 

The new changes in place are looking at about 45 minutes for 

those forms to be filled out, and, it is not filled out by the patient. 

It is filled out by the doctor. It is the exact same thing. You do go 

to your doctor, and you ask to have access to this drug. The doctor 

sends it to the FDA and it needs to be sponsored by the companies. 

The same holds true for ‘‘Right to Try.’’ You go to your doctor, 

you ask, and you have to get the company on board to do this. So, 

even if this passes expeditiously at the Federal level, nothing really 

changes with respect to access when it comes to the companies 

agreeing or not agreeing to provide. And, I know the FDA has done 

a really good job of getting that form changed. It took a little while, 

but that application process is changed. 

I also want to note that they did release, in that guidance, some 

information for companies, so that companies were not as adverse 

to providing these drugs for patients. And, they said very categorically in that guidance that adverse events that take place will not 

have a bearing on the clinical trial process. To support that, they 

released an audit, and in that audit, they were able to show that 

expanded access was not derailing clinical trials by any stretch of 

the imagination. 

There are still things that they could do. They still have a ways 

to go. I would recommend that they do another audit and look at 

the drugs that have passed and have a look at which adverse 

events took place during those clinical trials for compassionate use, 

as the drug was being passed, and how those adverse events really 

impacted the discussion—the approval process discussion. And, our 

hunch with our group at NYU Medical Center is that the people 

making these decisions understand that the people accessing these 

drugs under compassionate use, expanded access are the sickest of 

the sick. They are not your healthy sick people that get into the 

trials and they take that into account when they are looking at approving these drugs. 

Senator CARPER. So, let me see if I understand this. It is a question I just asked of my staff. If the FDA approved anybody who applied, who filled out this form, whether it is 45 minutes or whatever it takes to fill it out—and I understand it is filled out not by 
256 

the patient and not by the patient’s family, but by the patient’s 

physician. Is that correct? 

Mr. MCFADYEN. That is right. 

Senator CARPER. So, the notion that—and I think it was Dr. 

Neely who said these words, and I think he was quoting his daughter, ‘‘Treatment should not be up to somebody who has no involvement in my medical treatment.’’ But, the person who actually submits and signs, fills out and completes the document that goes to 

the FDA is the physician of the patient. Is that right? 

Mr. MCFADYEN. That is right. 

Senator CARPER. OK. So, let me see if I understand this. The 

FDA could approve access to experimental drugs to everybody who 

applies, whether it is in Stage I, Stage II, or Stage III. And, that 

does not mean that a patient is going to have access to those treatments. OK. I understand you are saying that is correct. So, then, 

if this legislation does not really get at the heart of the problem 

and the changes that the FDA has made—and I think they are significant and in the right direction—do not completely solve the 

problem, what should we do legislatively? I think you may have 

said this, but I just want to ask you to say it again. If this does 

not work—this legislation does not work—and if the FDA reforms 

are insufficient, what do we need to do? Or, is it something that 

maybe is beyond—— 

Mr. MCFADYEN. Well, I think, first and foremost, we need to pass 

the 21st Century Cures Act. That will pave a quicker pathway—— 

Senator CARPER. You say the 21st Century Cures Act? 

Mr. MCFADYEN. That is right, yes. 

Senator CARPER. Is that Senator Alexander’s legislation? 

Mr. MCFADYEN. I believe so. 

Senator CARPER. I think so, yes. 

Mr. MCFADYEN. I think that needs to be passed. I also think at 

the same time we need—— 

Senator CARPER. And, tell us why. 

Mr. MCFADYEN. Well, it is going to pave the way to have access 

to drugs approved a lot quicker. At the same time, I think we need 

to pass the Andrea Sloan CURE Act where—that forces companies 

to actually state online their expanded access, compassionate use 

policies—the criteria for inclusion. It will also force companies to 

have one point of contact at the company for somebody like Matthew to call and say, listen, I do not want a gmail address. I 

want—at Johnson & Johnson’s (J&J’s) website—and I want that 

one person to get back to me, immediately. If an application for 

compassionate use with a company is denied, it forces the company 

to explain exactly why. It actually lifts a level of secrecy at the 

company level. 

At the FDA, they really need to do a better job of communicating 

to the pharmaceutical industry exactly what adverse events do to 

the clinical trial process. In our study at NYU, we have seen that 

it does not actually impact it. But, Matthew is right. Only 1,200 

or 1,300 applications land at the FDA to be signed off on, and although 99 percent of those are approved, that is still only a small 

representation of the people that need access. 
257 

So, if ‘‘Right-to-Try’’ legislation gets passed at the Federal level, 

just as it has at State levels, we are not going to see the dramatic 

shift tomorrow that we hope to see. We just are not. 

I talked to a lot of industry folks before I came down here. I 

spent 16 hours a day for the past week talking to an unbelievable 

amount of companies throughout the United States—companies 

that I deal with seeking access as well as companies that I have 

never talked to before. And, they are as afraid of adverse events 

outside of the clinical trial setting taking place under expanded access as they are under ‘‘Right-to-Try’’ legislation. And, although the 

FDA cannot hold adverse events against the company and against 

the clinical trial because they do not have to be reported to them, 

there is a very good chance that adverse events under ‘‘Right to 

Try’’ will still be reported. It will be reported in the media. Companies that trade publicly have to include reports about anything that 

could impact the approval or the development of a new drug to the 

U.S. Securities and Exchange Commission (SEC). Oftentimes, those 

reports fall into shareholders’ hands, which fall into the general 

public’s hands, which get reported in the media. 

And so, it is a very real issue for them under both ‘‘Right to Try’’ 

and expanded access. And so, what we really need to do is work 

with these companies to ask how we can come together to make the 

changes that we need in order to provide access for our patients, 

in the now, so that we can have true help. 

Senator CARPER. Thank you so much. 

Chairman JOHNSON. Senator Paul. 

OPENING STATEMENT OF SENATOR PAUL 

Senator PAUL. I would like to start with a question for the Chairman. You said that there are plans to try to have this pass by 

unanimous consent? 

Chairman JOHNSON. I would like to do that next week. 

Senator PAUL. OK. And, you have no objections on our side of the 

aisle? 

Chairman JOHNSON. That is what we are hearing. 

Senator PAUL. OK. And—— 

Chairman JOHNSON. Maybe I do. 

Senator PAUL. No. Have you heard any public objections on the 

other side of the aisle? 

Chairman JOHNSON. No, I have not. 

Senator PAUL. OK. 

Chairman JOHNSON. But, I do not have a whole lot of cosponsors. 

I have one. 

Senator PAUL. Right. But, I think it is important to know that 

that is coming up, and I think it is important to know that our 

process is somewhat secretive, in the sense that people do not have 

to reveal when they are blocking legislation like this. But, it can 

be pushed, and people can inquire who the opponents are, and I 

think if people are going to oppose it, I think they ought to publicly 

oppose it and, if they have reasons, put those reasons forward. But, 

I think that the holds or the blocking of this should not be secret. 

And, I think every attempt should be made to make sure that that 

is an open process and that we know who wants to stop the legislation. 
258 

Chairman JOHNSON. That is why I will go down to the floor of 

the Senate next week and ask for unanimous consent. And, hopefully, whoever has an objection will come down and tell us what 

the objection is. 

Senator PAUL. Right. With that being said, I think that there are 

a couple of things to think about if we want to place our faith in 

the FDA doing things in an expeditious way. 

The recent controversy over the epinephrine auto-injector (EpiPen) costing $600, well, there has been a generic out there that 

applied in 2009. So, 7 years later, we have not gotten an approval, 

and it is over, I think, frivolous sort of complaints. Basically, it injects the drug. It injects the right dose. It works. And, yet the FDA 

is saying, ‘‘Well, it is not identical to the EpiPen device.’’ And so, 

for technical reasons, it is being held up. At least that is what I 

have heard in the press—7 years. So, I think we should not place 

a lot of faith in some sort of expeditious process. In fact, I think 

the whole FDA process needs to be overhauled, not just for people 

who are terminally ill but for everything. We do a miserable job at 

the length of time of of trying to approve drugs in our country. So, 

if we are going to wait back and say, ‘‘Oh, well, everything is just 

swimmingly well, just be patient,’’ I think that is a big mistake. 

I think the biggest part of the debate here, though, is over 

whether the compassionate use program works. And, I think that 

needs to continue to be driven home, whether it works or it does 

not work. And, I have learned a lot today about whether it works 

or it does not work. I think the fact that we have patients calling 

drug companies and they are not eligible but are not showing up 

in any statistic, it is not measurable, maybe, how large the number 

of ineligible patients is. 

My political director’s sister has pulmonary fibrosis. Her drug is 

not approved here. She actually is in a clinical trial because she 

lives in New York. But, if she lived in Bowling Green, Kentucky, 

my guess is it would be a little bit harder to get into one of these 

trials because we do not have a major university. But, the drug she 

is using in her trial has been on the market for 10 years in Japan. 

Why in the world do we not use drugs that have been on the market to the general public? A Phase III trial might have 1,000 patients. How many people live in Japan? A hundred million people? 

It is a rare disease, but maybe there are 10,000 people in Japan 

using the drug. Why are we not using that data? We give the FDA 

the option to use the data, but they choose not to. And, this is the 

problem. We come to this legislation—it comes forward, and I will 

try to put a word in that the FDA should or shall do this, and everybody will say, ‘‘Well, let us just give them the option of using 

it, let us trust the FDA to do the right thing.’’ 

Well, no, the FDA does what they have always done—and that 

is slow-ball and slow-roll things, and so, we have instance after instance—we do not have like thousands of instances of the FDA saying, ‘‘We got it done’’. We have thousands of instances of it taking 

5 and 10 years. 

But, we also have to look at the whole FDA process. The EpiPen 

has a 38-year patent. Why in the world would we do that? They 

tweak their patent on the device. OK, it delivers it slightly faster, 

quicker, or differently, the needle is slightly longer—and we give 
259 

them another 10 years. The EpiPen is 38 years. They got the approval in 1987. The injector was actually approved in the 1970s. 

And, their patent is not going to run out until 2025. 

The other thing I have learned, today—or was reinforced for me 

is—Matthew talking about the individualization of treatment. We 

may be entering into an age, if we are not already there, where we 

are never going to have 1,000 people get the same treatment because it is going to be individualized to their exact genetic disorder 

if it is some gene that is wrong in his body. Maybe the treatment 

is going to be specific to him. There are never going to be 1,000. 

But, ultimately, the way I look at this issue is, look, we live in a 

free country. My goodness, shouldn’t people be free to try? And, 

will it always work? No. But, I mean, ultimately, if you have ALS, 

my guess is that you also want trials to go on. It is not like you 

are against trials to go on to see what actually works. But, if we 

prevent the trials and we prevent people from trying, we will never 

know. 

So, I commend the Chairman for putting this forward and wish 

you the best of success. 

Chairman JOHNSON. Thank you, Senator Paul. I do want to point 

out that Senator Donnelly and Senator Manchin are the two Democrat cosponsors we have. 

Mr. Garr, you talked about the ability of ‘‘Right to Try’’ to accelerate research. Can you just kind of speak to that? And, I want to 

keep this relatively short and then I will give Senator Carper a 

chance. I want to ask that question. But, then I also want to get 

you guys thinking about this. Where is the real harm? Obviously, 

Mr. McFadyen, you are not for this, but what is the harm of this? 

I am not saying it is a panacea. I am not saying it is going to work 

great. You have the problem of determining the cost of these 

things—incredibly expensive. But, what is the harm in doing this, 

in terms of—versus the benefit of giving people hope? But, again, 

talk about the accelerated research. 

Mr. GARR. Sure. We did, as I said, 15 patients in the first trial 

and 25 patients in the second trial. If we had delivered this drug 

through a ‘‘Right-to-Try’’ opportunity in any of the States that 

passed it, it would have been the exact same surgeons doing the 

exact same surgery with the exact same product. In fatal diseases, 

there are no healthy volunteer trials, right? So, every patient, 

every bit of data you get is important. And what I would also say 

is that no company looks at a drug and says, ‘‘Gee, my market for 

this is the label I get from the trial,’’ right? The very specific narrow group. No. Everyone looks at the development and says, ‘‘OK, 

this is how we can create a trial and get this passed. And then, 

how do we expand the label? ’’ Right? 

And so, every pharmaceutical company—all of your companies in 

Delaware, right?—all have the same mantra, today, which is, ‘‘Fail 

fast.’’ Right? They do not want to spend $2 billion in 10 years to 

find out it does not work. Right? More data is always better. More 

data is always better. It always accelerates research. 

And, I would also just like to point out that there is a relatively 

easy answer. In Japan—and we have moved all of our cell therapy 

there—they adopted a law where, if you have a fatal disease, you 

can do a trial, and as long as it passes the safety test and shows 
260 

some reason to believe it could work—not statistically significant 

efficacy. The trials are not powered to show efficacy. But, they have 

to show safety. They then give you a transitional approval. You can 

then commercialize for 5 years—even 7 years—while you continue 

to do trials and continue to collect data. That gives access to everybody who wants it with a minimum safety net of safety established. 

And, I will tell you, it has taken the whole cell therapy industry 

and turned the map upside down and pushed everyone to Japan. 

Right? 

Now, the 21st Century Cures Act is kind of a kinder, gentler, and 

weaker model of that, but it does not come right out and do what 

the Japanese did. That is the way you solve this problem if you 

really want to. 

Chairman JOHNSON. And, of course, with ‘‘Right to Try’’, you only 

get drugs that have passed Phase I, which is the safety standard. 

Mr. GARR. Very safe. 

Chairman JOHNSON. Assemblyman Calderon, you have been trying to jump in here. 

Mr. CALDERON. Thank you, Senator. I think there needs to be an 

important distinction made when it comes to access, because we 

are looking at access, right now, in terms of being able to get the 

drug—but that is not necessarily the case. You also have to look 

at access in terms of time. If you are given a diagnosis of a year 

to live with a terminal illness, well, right now the new expedited 

process, all they did was shorten the time for the application from 

100 hours to 45 minutes. But, there is still a 30-day waiting period. 

And, now say that application is returned with a misspelling. 

Maybe they forgot to fill something out. You send it back, and the 

30 days starts all over again. If you are given a year to live, 30 

days is your life. And, the point is that with my bill in the legislature—in the assembly—you could do that within a week. That is 

why State laws, in terms of ‘‘Right to Try’’, are so important. 

Mr. MCFADYEN. And, can I just address that? I am sorry to interrupt. It is not 30 days for the FDA to get these applications back. 

Sometimes, it is just overnight. Sometimes, for compassionate use, 

expanded access, it is done over the telephone. So, it is not 30 days. 

They are not going to care about a misplaced ‘‘I’’ or an ‘‘I’’ before 

an ‘‘e.’’ That is not how this works. It does get done in a very rapid 

fashion. 

Chairman JOHNSON. And yet, can you explain why Dr. 

Delpassand could not expand his own trial to patients that needed 

the therapy? 

Mr. MCFADYEN. No, with a 3-minute video I cannot. 

Chairman JOHNSON. Go and look at the 20-minute video. 

Mr. MCFADYEN. I will. I most certainly will. 

Chairman JOHNSON. Give him a call. 

Mr. MCFADYEN. But, what I will say is that he is in the 1 percent that did not get to move forward. So, when 99 percent do, 

there is access through that. It is not the FDA that we continue 

to vilify here. It really is the matter of the companies not providing 

access. 

Chairman JOHNSON. Matt, do you have something? 

Mr. BELLINA. Yes, Senator, thank you. We are all hovering 

around something—a great example that I really think illustrates 
261 

what we are all talking about here. There is a drug out of Japan 

that has been approved for ALS for about 2 years now. It is called 

Radicut. And, to the credit of the FDA, the company applied for a 

new drug application (NDA) based on Japanese data. You have 

about 10 years of trials and 2 years of market. And, the FDA accepted the NDA—— 

Senator CARPER. I am sorry, NDA? 

Mr. BELLINA. New drug application. Sorry, Senator. 

Senator CARPER. Thank you. 

Mr. BELLINA. So, the company, Mitsubishi Tanabe Pharmaceuticals, asked for a 6-month review out of respect to the FDA. 

The FDA came back and said, ‘‘We will look at it, but we need 10 

months.’’ This is a drug that has been essentially in humans for 

about 12 years and, in that 10 months, we are going to lose about 

5,000 ALS patients. Excuse me. So, you can see—I am sorry. I get 

a little emotional about that. That drug should be, in my opinion, 

already in a Phase IV market study, and it really illustrates—— 

Senator PAUL. And, how far are we into that? How far are we 

into that 10-month cycle? 

Mr. BELLINA. We are about 4 weeks in, Senator. 

Chairman JOHNSON. Does anybody else want to quickly comment 

before I turn it over to Senator Carper? 

[No response.] 

Senator Carper. 

Senator CARPER. Mr. Garr, you mentioned that the expanded access program at the FDA limits what a company can charge patients for treatment. How do ‘‘Right-to-Try’’ laws ensure that patients can afford their treatments? 

Mr. GARR. Yes. All of the issues around cost and access are unresolved on this, but they are no different than they are for approved 

drugs. Right? So, in other words, how do we know that everybody 

can afford Genentech’s new vaccine? I mean, we have the exact 

same issues for these unapproved drugs that we have for approved 

drugs. So, yes, there are issues. They are all resolvable. There are 

people in this industry who just spend all day, every day working 

on those answers. I cannot tell you right now what our therapy 

would have cost an ALS patient. I know what it costs us to do a 

trial, right? I cannot tell you that. But, the fact is that whether we 

are doing it under a compassionate use, where we have to give it 

to them basically without charging, we have to try and get the surgeons not to charge, and we have to try and get the anesthesiologist not to charge, and go through that whole process—or if we 

figure out what everybody is going to charge for a particular thing, 

that is no different than it will be when it becomes an approved 

drug. 

Senator CARPER. I am going to ask you to hold it right there. 

What help, Mr. Garr, should be offered to patients and to pharmaceutical companies to ensure that patients can afford these drugs, 

and then, that companies can sustainably provide the treatments 

that patients are seeking? 

Mr. GARR. I think there are two basic things that have to happen. First, companies have to be able to charge for it—and, yes, 

there will be companies that still will not do it. There will be companies that will not offer their drugs. There is nothing in this Act 
262 

which forces companies to offer their drug under compassionate use 

or under ‘‘Right to Try.’’ 

And, the second thing is there are, I believe, the last time I 

looked at it, about a dozen States that have already passed laws 

that require insurance companies to cover experimental treatments 

for certain types of cancer. So, if you are in a cancer trial in Kansas, for instance—right?—and it is at least a Phase II trial and you 

have to pay for it, it is just like it was an approved drug, in terms 

of the insurance company. I think that is the second part of the answer. Again, the market has to work. The insurance industry, we 

have all kinds of people working on drug pricing and approvals 

throughout this entire industry. And, I would add that we are an 

industry that is 100 percent based on the presumption that all of 

these issues can be addressed. People may not like the way they 

are addressed. Not everybody is happy with the answers. But, in 

the end, who gets drugs, what they are paid for, and who pays for 

them—we work that out for every approved drug on the market. 

So, there is no reason we cannot work that out for unapproved 

drugs also. 

Senator CARPER. Thank you very much. 

Mr. McFadyen, you have worked on behalf of patients. You mentioned patients and families. As a patient advocate, I just want to 

thank you for what you do. And also, Ellen, for your support as 

well, as his wife, trying to help individuals gain access for rare disease treatments. Have you ever worked with a patient who has received drugs under a ‘‘Right-to-Try’’ law? 

Mr. MCFADYEN. No, not at all. And, that is what we continue to 

say, that there is no concrete evidence of patients ever receiving a 

medication under ‘‘Right to Try’’ in the United States that they otherwise would not have received under expanded access laws. 

And, there are 137 million people that have access—supposed access—under ‘‘Right to Try,’’ and there is no evidence that it is 

working—that it is moving forward. So, in my personal experience, 

no. 

I can tell you that, the disease families that I represent—the 

rare disease folks—many of them are watching the live feed right 

now, and we are all united in the belief that, should legislation be 

passed, today, the landscape for them looking at access to medications, tomorrow, will not have changed. It is not the programs that 

are the issue right now. It is the companies and their fears under 

expanded access and adverse events—but also under ‘‘Right to 

Try.’’ 

Senator CARPER. Just a follow-up question, if I could, Mr. 

McFadyen. What has been your experience, if any, in working with 

the FDA on behalf of patients seeking access to experimental medicines? 

Mr. MCFADYEN. Yes, I have actually had a very good working relationship with the FDA—they have been very responsive to our 

needs. Richard Klein is the patient support liaison director at the 

FDA, and he returns emails—actually, I was shocked at how quickly I got responses from them, at first, and I am not anymore. They 

get information back to us very quickly. They help walk us through 

situations where we need information and that sort of thing. They 

are currently putting in place sort of a personal concierge service 
263 

to help physicians fill out that 45-minute form to make sure that 

it is done right so that they can have that on-the-phone conversation review—an overnight review type of thing. And, from what I 

understand, as well, your next witness, Dr. Lurie, is seen within 

the patient advocacy community as somebody who is a patient advocate at heart with the FDA and who really wants to try and advance access to medications for my kids—for our patients—as fast 

as possible. 

Senator CARPER. I understand that Johnson & Johnson recently 

established a new program to help patients secure, I think, number 

one, information to experimental treatments but also access to 

those experimental treatments. I do not know if you are familiar 

with their program, but if you are, could you talk about it, please? 

Mr. MCFADYEN. Yes, actually, Johnson & Johnson looked at this 

issue of access to medications long and hard and understood that 

things needed to move forward quickly. And so, what they put in 

place was something they called ‘‘CompAC.’’ They take all of the 

expanded access and compassionate use requests for one certain 

drug. It is a trial program right now that has just run its course 

and it is going to be expanding soon. And, they take those applications, and they send them on to a group at NYU Medical Center 

that looks at these applications. The applications are free of bias, 

so decisionmakers in that 10-person committee, which is made up 

of medical ethicists, researchers, physicians, and that sort of 

thing—Art Caplan leads that group. They look at those applications, and they make a recommendation back to J&J on whether 

a patient should be approved or denied access to that experimental 

drug. 

Last year, alone, in the 6 months that it was on, I think they 

took in 100 or so applications. Sixty two of them were approved. 

Sixty of them were recommended by the committee to move forward back to J&J, and after that recommendation for 60, two more 

got in a little bit more medical information to the company, and 

they were approved. The other ones that were not approved were 

not approved because the patients had not exhausted all other avenues of available treatments. 

And so, they used this program to make it extremely expedited 

and free from bias from pharmaceutical eyes based on costs, etc. 

And, they allowed others to recommend for them. It could be a pivotal turning point for companies, with respect to access to medications, because if this is a model that they can use and use successfully—a big company like J&J—and they are going to expand this 

process in the very near future for other drugs and that sort of 

thing. That is what we really need to do. 

Taking that example, I know BioMarin Pharmaceuticals just announced an early access program for a disease that I actually deal 

with quite extensively, Batten disease. Batten disease is one of the 

worst childhood diseases I have ever seen. Over the course of a 

year or two, patients lose all mobility, all access to their extremities, and they enter a vegetative state and pass away very quickly. 

BioMarin, after Phase I–II, opened up an early access program. 

They are trying to get as much of the drug out as is feasibly possible for these patients, and they are taking a similar path forward 

to J&J by allowing the investigators to have their own committee 
264 

and their own set of ethics and criteria. So, they are not making 

the decisions anymore—and I am seeing this happen more and 

more with pharmaceutical companies looking at the problems that 

currently do exist with access to medications. 

Senator CARPER. Thank you so much. 

Chairman JOHNSON. Senator Paul. 

Senator PAUL. I just have a really quick question. I wanted to 

reemphasize something Mr. Garr said and make sure I understand 

it. Under the compassionate use program, no money can change 

hands—not even for costs or anything? 

Mr. GARR. No, there are mechanisms for recouping some costs, 

but the way they define cost is very different than the way a company thinks of it. A good example is ours. We literally have to send 

a cell technician up to Charles River Lab in Pennsylvania, have 

him work there for a day, do what he has to do, and ship the cells 

somewhere else, right? That is a very tiny part of the opportunity 

costs we lose when our Chief Science Officer (CSO) has to spend 

24 hours being a cell technician. 

Senator PAUL. Right. And, I guess the only other point I would 

like to make, quickly, is that, if you allow for profitability, I am all 

for that because profitability does drive innovation. There was an 

economist after World War II, Joseph Schumpeter, and he put it 

this way: ‘‘The miracle of capitalism is not that queens have silk 

stockings, but that factory girls do.’’ But, the way that is driven is, 

initially, only the queen may be able to afford it. And so, allowing 

money to go into the development of drugs, both through individuals or through companies, is a good thing. When calculators first 

came out, no poor person could afford them. Now, you are virtually 

given a calculator with your phone, basically. When most things 

are innovated—Lasik surgery came out, it was very expensive. 

Only the rich could afford it. But within years, if you allow capitalism to work, the price comes down. But, the driving force of innovation is allowing capitalism and pricing to work. And so, I think 

that is an important distinction between what we are talking about 

here and the compassionate use program—and a limitation of the 

compassionate use program. 

Thank you. 

Chairman JOHNSON. Thank you, Senator Paul. I would also point 

out, if you are talking about costs, it would be nice if it did not cost, 

on average, $2.6 billion to bring a drug successfully to market. 

Just really quickly, if anybody has a final—OK, but quickly. 

Mr. CALDERON. Thank you, Senator Johnson. Just three quick 

points. 

In terms of the 30 days of the application process—the new expedited application process with the FDA—it is 30 days if the FDA 

has any questions of the physician or the manufacturer. 

In terms of statistics regarding ‘‘Right-to-Try’’ legislation, today, 

any statistics that you would gather from ‘‘Right-to-Try’’ laws, 

today would be, I believe, inappropriate to use because, when I introduced this bill last year, there were less than 10 States that had 

this on the books. Now, there are over 30. So, you would not have 

any properly measurable data to look at. 

Chairman JOHNSON. And, until the Federal legislation provides 

that overall protection, they are not going to work. It does not sur-
265 

prise me at all. There are not very many people like Dr. 

Delpassand who are willing to take that risk. 

Mr. CALDERON. Right. And, in terms of costs, well, what is the 

other alternative, having to move to another country in order to get 

access to these drugs? And so, in terms of costs, well, yes, it is 

going to be more expensive even if you have to move to another 

State that has ‘‘Right-to-Try’’ laws on the books. It is better to stay 

in your own State to have that opportunity to do it at home. 

Chairman JOHNSON. Quickly, anybody else? Mr. Garr. Oh, I am 

sorry. Mr. Neely. 

Mr. NEELY. Yes, I think, just after this access, this is an avenue 

that we need. Patients need it and the doctors need it. Thank you. 

Chairman JOHNSON. Matt. 

Mr. BELLINA. Yes, Senator. I think that Andrew has done a really good job of laying out the obstacles, and I think there really is 

a lot of work that is going to need to be done even after the passage 

of this legislation. But, I think that you brought up a great point. 

What is the overt risk? What is the downside of this legislation? 

I think, you don’t not try for a first down because it is not in the 

end zone—if anybody is into football. So, that would be my one 

question. 

Chairman JOHNSON. Thank you, Matt. 

Just very briefly. 

Mr. MCFADYEN. It will be very brief. Senator Paul is no longer 

here, but I did want to address the idea of access. With all due respect, my son can wait until he can save up and afford a calculator. 

He cannot afford $200,000-a-year or $300,000-a-year drugs that can 

be charged under ‘‘Right-to-Try’’ legislation. Direct costs are direct 

costs and providing access should not be about making money. 

Chairman JOHNSON. Again, I just want to thank all of the panelists and I appreciate your testimony. With that, we will call our 

next panel, Dr. Lurie. Thank you. 

Senator CARPER. Thank you all. 

[Pause.] 

Chairman JOHNSON. Dr. Lurie, it is our tradition to swear in witnesses, so if you will please rise? Do you swear the testimony you 

will give before this Committee will be the truth, the whole truth, 

and nothing but the truth, so help you, God? 

Dr. LURIE. I do. 

Chairman JOHNSON. Please be seated. 

Our next witness is Dr. Peter Lurie. He is the Associate Commissioner for Public Health Strategy and Analysis in the Office of the 

Commissioner at the Food and Drug Administration. Prior to that, 

Dr. Lurie was Senior Advisor in the Office of Policy and Planning. 

Before coming to the FDA, he was deputy director of Public Citizen’s Health Research Group. He had an earlier academic career 

at the University of California, San Francisco (UCSF), and the University of Michigan (UM). Dr. Lurie. 
266 

1The prepared statement of Mr. Lurie appears in the Appendix on page 307. 

TESTIMONY OF PETER LURIE, M.D., M.P.H.,1 ASSOCIATE COMMISSIONER FOR PUBLIC HEALTH STRATEGY AND ANALYSIS, 

FOOD AND DRUG ADMINISTRATION, U.S. DEPARTMENT OF 

HEALTH AND HUMAN SERVICES 

Dr. LURIE. Good morning. Mr. Chairman, Ranking Member Carper, and Members of the Committee, I am Peter Lurie, as you have 

heard, with the Office of Public Health Strategy and Analysis at 

the FDA. Thank you for the opportunity to be here to discuss expanded access to investigational products. 

As a physician, I have personally witnessed the suffering—and 

we have heard much about that today in really heart-wrenching 

testimony—and I have witnessed the dilemmas facing patients and 

their families when they are confronted with serious or life-threatening conditions and have limited treatment options. In these circumstances, investigational products may be their only hope and 

the FDA recognizes that. In many instances, patients with lifethreatening diseases are more willing to accept the risks associated 

with investigational products than other patients would—especially 

if they have no other available options. 

And, that is why, for over two decades, the FDA has had in place 

a system to help patients gain access to investigational products. 

And, it is functioning well. The treating physician must first approach the pharmaceutical company. If the company agrees to the 

physician’s request, the physician can then apply to the FDA for 

permission to proceed. Should they do so, they are highly likely to 

be allowed to proceed. The FDA has authorized more than 99 percent of single patient expanded access requests between 2010 and 

2015. And, despite what we have heard, emergency requests are 

usually granted immediately over the telephone and non-emergency requests are processed in a median of 4 days. The 30 days 

means that the application can proceed without the FDA if we exceed 30 days. It does not take 30 days. It takes either the same 

day for emergencies or a median of 4 days for non-emergencies. 

Now, access to investigational products requires the active cooperation of the treating physician, the FDA, and the industry. It 

appears that pharmaceutical companies turn down considerably 

more applications from physicians than does the agency. Mr. 

McFadyen spoke to this when he gave you the data from the Johnson & Johnson experience. They have turned down 98 applications 

for one drug in a 6-month period. Now, the FDA has turned down 

66 applications—fewer, for all of the drugs that are out there, 

among the thousands that it has received. So, they have turned 

down 98. We have turned down only 66. And so, on this, I think 

Mr. Garr’s testimony was very much on point as well. 

Now, we continue to work avidly to improve the expanded access 

program because everything can be improved. The FDA established 

an expedited telephone process for daytime and after-hours emergency requests for expanded access—and you have heard about the 

success of that program. In 2009, we revised the application regulations to make the process and the responsibilities of physicians 

clearer. 
267 

In June 2016, in response to feedback from physicians that completing the two expanded access forms was time-consuming, the 

FDA developed and released a new simple form for individual patient expanded access—and here it is. And, I am proud to say, I 

led the group that pulled this together. The form is estimated to 

take only 45 minutes to complete and requires just a single attachment, whereas, the previous form required up to eight. 

At the same time that we put out this new form, we released 

step-by-step instructions on how to complete it and two additional 

guidances—one of which addressed the charging issue. Simultaneously, we revamped our expanded access website and we produced fact sheets for physicians and patients. 

However, even patients with serious or life-threatening conditions require protection from unnecessary risks, particularly because, in general, the products that they are seeking through expanded access are unapproved—and may never be approved. Moreover, the FDA is concerned about the ability of unscrupulous individuals to exploit such vulnerable patients—and we see this. Thus, 

with every request, the FDA must determine that the potential patient benefit from the investigational drug justifies the potential 

risks, in the context of the disease, to be treated. And, that is why, 

even as we permit more than 99 percent of applications to proceed, 

we make meaningful changes to about 11 percent of them, generally to ensure patient safety, including changes in dosing, safety 

monitoring, and informed consent. 

The FDA’s expanded access process strikes a careful balance between helping to facilitate patient access to investigational therapies and the need to protect patients and promote the public health 

through science-based regulations—as Mr. Bellina points out. Upsetting this balance has the potential to expose patients to unreasonable risks and stymie the development of medical products that 

could benefit us all. 

To sum up, the FDA’s expanded access program allows almost all 

applications to proceed. It improves many of the applications that 

we receive and it does so expeditiously. At the same time, it protects vulnerable patients from potential harm from drugs that may 

not be effective and from exploitation by unscrupulous individuals. 

It also maintains the integrity of the clinical trials process because, 

in the end, the very best way to hasten access for patients to safe 

and effective drugs—for the largest number of patients, not just 

those in expanded access programs—is to get the drug approved. 

That concludes my comments. I am happy to take any questions 

you may have. 

Chairman JOHNSON. Thank you, Dr. Lurie. 

You talked about undue risk. It is true, under this bill, that 

these drugs will have already passed Phase I, which has basically 

certified the safety of the drug. Can you reconcile those? What is 

the added risk if the FDA has already said it is a safe drug? 

Dr. LURIE. We have not, sir. At the end of Phase I, we have only 

seen a few dozen patients being treated. And so, although we have 

some preliminary information about safety, we are far from certain 

that this is a safe drug. We still have Phase II to go through, where 

we gather additional safety information, followed by Phase III, in 

which we get still more. So, Phase I is a very long way from estab-
268 

lishing effectiveness and it is also a long way from establishing 

safety. 

Chairman JOHNSON. Well, you never completely establish safety. 

I mean, even once a drug is totally approved, you are going to continue to do that monitoring. 

Dr. LURIE. Certainly, but there is a world of difference between 

a couple of dozen patients and the many hundreds to thousands 

who will, ultimately, be exposed during Phase III trials. 

Chairman JOHNSON. Can you explain why Dr. Delpassand was 

not able to increase the number of patients he was able to treat? 

Now, here is a situation where the manufacturer has actually 

agreed to provide the drug. 

Dr. LURIE. Right. 

Chairman JOHNSON. I would assume—it seems to be the real 

stumbling block in whether it is expanded access or ‘‘Right to Try’’ 

that—because companies do not have protections against adverse 

effects—they do not have liability protection. I want to talk a little 

bit about the restrictions, in terms of being able to charge patients. 

But do you know what is pulling off, in terms of down there in 

Texas? 

Dr. LURIE. I really cannot speak to that, sir. I have only seen the 

video for the first time this morning, so I cannot speak to the details of that. And, as I think you understand, these are pre-market 

drugs and the FDA is restricted in its ability to be able to discuss 

them. 

Chairman JOHNSON. Can you understand just the human frustration, though, when you have a doctor apparently, again, working 

with patients, having access to a drug, treating, getting up to his 

limit of 150 patients, and having another almost 100 patients there 

that he thinks can benefit—and, I am sorry, bureaucrats in Washington, D.C., saying, ‘‘No, we are not going to let those extra 100 

patients have that hope’’ ? Can you speak to that? 

Dr. LURIE. Yes, well, in principle, I could understand that. I cannot speak to his situation, but I can speak to the general situation, 

which is that, 99 percent of the time, when a doctor tries to get access for their patients, they succeed. And, the times that they do 

not, I must tell you, are really outlier situations. I mean, those are 

the situations where we—meaning our medical reviewers, who 

know as much as anybody about the drug, right? They know more 

than the doctor because we have seen the information coming in, 

perhaps from foreign countries, and unpublished results—we see 

that stuff. So, we may have additional information, and so, based 

on that, we may believe the drug is unsafe. Based on that, we may 

believe that there is no reasonable hope that the drug will work. 

Or, we may know that the company is not making the drug in a 

way that is safe for patients. 

Those are the outlier reasons. That is 1 percent, right? Most of 

the time they are going through, but, when they do not, it is usually a fairly flagrant thing because we do not exercise that authority very often. 

Chairman JOHNSON. What is the FDA’s intention, in terms of 

how it deals with someone like Dr. Delpassand, who is operating 

under Texas’ ‘‘Right-to-Try’’ law? Is there going to be any enforcement action against doctors that have the courage to do that? 
269 

Dr. LURIE. Yes, well, Senator I cannot really speak to what enforcement action we might take. We are a science-based organization—and we are interested in data. And, to the extent that data 

is generated—and that it might come to our attention—we are interested in the data that there might be. 

Chairman JOHNSON. In your testimony, you use the phrase ‘‘exploit vulnerable patients.’’ Can you talk about what you mean by 

exploiting vulnerable patients—people, like Matt, who are trying to 

get access to a drug to give themselves some hope? 

Dr. LURIE. Yes. Look, we understand that patients, like Matt, are 

looking for hope. We understand that. We understand how desperate they can be. But, it is that very desperation that makes 

them vulnerable to exploitation. All someone needs to do—— 

Chairman JOHNSON. Can I say, who are you—who is the FDA— 

to make that decision for them? 

I am sorry. Who are you to tell Matt that you are going to protect 

him from exploitation when he has no further hope? 

Dr. LURIE. Well, Senator, with respect, I feel like that is the very 

responsibility with which this Congress has charged us. I think we 

have been asked to look after patients—and we feel that that is exactly the responsibility that we are exercising. 

Chairman JOHNSON. I have no further questions. 

Senator CARPER. I want to dwell on the last question that the 

Chairman asked. In your testimony, I thought I heard you say the 

words ‘‘protect patients against unscrupulous individuals who 

might want to take advantage of those people.’’ Do you have any 

examples of that you might be able to share with us, either on the 

record or here, today? 

Dr. LURIE. Well, Senator, as I said, the problem is that we cannot go into specific applications. But, I think that someone just has 

to take a look at the Internet and see the kinds of things that are 

being hawked there, and how often they focus on very desperate 

patients, to realize that this is a very real issue. 

Senator CARPER. Alright. Thank you. Matt raised, earlier, when 

he was testifying—I think it was Matt who mentioned an ALS drug 

that had been approved, in Japan, maybe a couple of years 

ago—2 years ago—and that there was an effort to see if that drug 

could be made available here. I think, initially, the FDA said it 

needed 6 months to look at this—6 months—and then, they said, 

‘‘No, we need 10 months.’’ Could you just talk about 6 months as 

opposed to 10 months—and, when you have some country, like 

Japan, that has been allowing a drug like this to be used for a couple of years? What is the approval process like at the FDA? How 

can we expedite that? Or can we? 

Dr. LURIE. OK, so I think there are two issues. First is the 6 

months versus the 10 months. So, those are goals that are in what 

is called our ‘‘user fee legislation.’’ They are the product of negotiation between the FDA and industry. And, there is a priority review 

process and a standard review process. The priority review is for 

those that would be expected to show a particular benefit—and 

that is 6 months. Otherwise, it is 10 months. About half go through 

each. That is the rough proportion between the two. That is legislation, in the end, that is ratified by the Congress—so we follow 

those. We have to get 90 percent—best we can—90 percent of the 
270 

applications for priority review in 6 months and for standard review in 10 months. And, we have met those goals now for a number of years. 

So, that is the way it works. There is a definition. The FDA has 

guidance on it that explains the difference between the two. And, 

I expect that we did our best to follow that guidance in deciding 

how to assign that particular drug. 

Now, with respect to the issue of Japan or foreign countries, in 

general, I think, there is an old story about how the FDA is slow 

and how drugs are on the market in foreign countries and American patients cannot get access to them. That is a very old story 

and, frankly, an outdated story. It just simply is not true. 

Now, 57 percent of all drugs in the last several years that have 

come on the market have come on the market in this country first. 

Now, there are about 200 countries in this world, and—— 

Senator CARPER. That is over half of all of the drugs? 

Dr. LURIE. Yes, over half of them. They are in 200 countries and 

one country is first most of the time. 

Senator CARPER. And, that is us? 

Dr. LURIE. And, that is us. And, just to be colloquial about it, if 

you go back to the Olympic Games and you look at how the Americans did, everybody said, ‘‘Well, what a great success. The Americans brought home this treasure trove of gold medals,’’ which they 

did—and everybody is proud of that. But, they only won 12 percent 

of the gold medals. I mean, the FDA is doing better than that. 

Senator CARPER. OK. Thank you. 

Dr. Lurie, let me just ask—the FDA has released information to 

clarify that outcomes in expanded access cases are not treated the 

same way outcomes from clinical trials are treated. Do adverse 

events from expanded access cases ultimately affect the final outcome of the FDA’s review of that drug? The FDA has approved almost 100 percent of expanded access applications, as you have 

mentioned. But has the FDA ever put a hold on an ongoing clinical 

trial as a result of an adverse event from a patient using expanded 

access? And, how quickly were these holds resolved? 

Dr. LURIE. OK. So, let me answer that question sort of generally 

and then specifically. 

The general answer is that our folks—our medical officers, who 

are experts at reviewing drugs—they understand that the expanded access situation is very different from the conventional clinical trial situation. The patients who are in it are different in expanded access. They are more likely to be sick. They are more likely to have other conditions. They are more likely to be on other 

drugs. There is no comparison group—right?—in general, in the expanded access program as well. 

So, we know that any particular adverse event that comes in 

should be treated, in most cases, as an anecdote and should be afforded the appropriate weight, which, frankly, is not a very high 

weight, because it is just not—it is so atypical. And so, for that reason, I think that people should place some trust in the fact that 

medical officers can distinguish between these two very different 

sets of circumstances. 

Now, we know that people are worried about it. We have heard 

this concern raised several times during the previous panel. And, 
271 

in fact, in one of the three guidances that I mentioned we released 

back in June, we addressed this question, specifically, in the socalled question and answer (Q&A) guidance. It is one of the three. 

Question 25 is about exactly this question. We explain how the 

FDA’s medical officers understand the context and will apply the 

appropriate weight. Now, that is the general answer. 

The specific answer is that we took this question seriously 

enough that we tried to gather some actual data. We went back 10 

years and we looked at all of the applications that had come in. 

There were about 11,000 of them. And, they were—I am simplifying, slightly, here—for about 1,000 drugs—1,033, to be exact. 

And, we asked ourselves how many times had an adverse event 

that occurred in expanded access resulted in what we call a ‘‘clinical hold’’ on an application—right?—an ongoing manufacturer’s 

application. Out of 1,033, over 10 years, we found two. OK? They 

were partial holds. Once the issues were resolved, then the program was allowed to continue. 

So, we do understand this issue. We would not overweight these 

anecdotal pieces of information. But, we need to have that information all the same. OK? 

What we do not want is a circumstance where the FDA does not 

receive an adverse event report. Or, if they receive it, they are 

forced to ignore it. I mean, for a scientific agency, it is just terrible 

for us to have, perhaps, in rare cases, valid scientific information 

and then, have to ignore it. Let us say the drug comes on the market, and then, after approval, when thousands of people start to get 

the drug, that very same adverse event now occurs and we knew 

about it back then, but we could not address it? I mean, we will 

probably be right here before this Committee again. 

Senator CARPER. Thank you. If this legislation is not—it is well 

intentioned, very well intentioned legislation. 

Dr. LURIE. Yes, sir. 

Senator CARPER. If this is not the answer to this challenge, this 

conundrum that we face, what should we do that we have not 

done? 

Dr. LURIE. Well, I think that some people have talked about 

some transparency on the part of the pharmaceutical industry. I do 

think that would be helpful. Johnson & Johnson has been a leader. 

I think more and more we are seeing companies put their expanded 

access policies, either in general or with respect to particular 

drugs, on their websites. I think those things really help. We are, 

as some others mentioned, exploring the possibility of a navigator 

to help folks get through the process. 

As was also said, we have folks who are committed to doing 

that—who are dedicated to just that—day in and day out. And, 

they hold people’s hands through this process. They understand 

which companies have drugs that are available through expanded 

access. They understand which parts of the FDA have jurisdiction 

over that drug. They understand what form needs to be filled out 

and how to do it. And, they hold your hand through the whole process. 

So, we are reforming ourselves, internally, to make things better. 

The form is the biggest symbol of that, to be sure. And, I should 

say, parenthetically, 100 hours—I mean, as was pointed out, the 
272 

form was kind of a repurposed form. It had been for commercial 

purposes before. And, our form indeed said 100 hours. But, nobody 

believed that it actually took the 100 hours. I mean, do you know 

any doctor—or does your doctor ever spend 21⁄2 weeks on you? 

Right? A hundred hours? It is inconceivable. So, that was never 

happening. OK? But now, all the same, we took the criticism seriously. And, to the extent that that misinformation had dissuaded 

people from applying, we have gone and reformed the form. It took 

a bunch of work. It is now done and people are starting to use it. 

Senator CARPER. Mr. Chairman, I would just say that the folks 

at the FDA have a hard job. A hard job. Thank you for doing it. 

Chairman JOHNSON. Senator Lankford. 

OPENING STATEMENT OF SENATOR LANKFORD 

Senator LANKFORD. Dr. Lurie, thank you for being here. Let me 

pick up where you just left off there with the 100 hours for the 

form. It is my understanding that the 100 hours was not the time 

needed to complete the form, rather, it was the time needed to 

gather the information required for the form. The form was pretty 

straightforward, just as a checklist, but the form implied that it 

would take 100 hours to gather the information needed for the 

form. Is that accurate or not accurate? 

Dr. LURIE. That is right. Under the Paperwork Reduction Act 

(PRA), when we make these estimates, the estimate that now 

says—on the back of this form, 45 minutes, it is not just, literally, 

filling it out. It is all of the associated materials, all of the attachments, and so on and so forth. And, I want to tell you, I took a 

look at that form. I am a physician and I work at the FDA. And, 

I thought, if you are a medical doctor (M.D.) out there, who is 

working hard and dealing with expanded access on a frequent 

basis, it was pretty intimidating. I agree with that. And, that is 

why we pulled together this group—exactly to address that concern. 

Senator LANKFORD. So, the 45 minutes is not just completing the 

form. It is gathering information—— 

Dr. LURIE. Oh, it is everything. 

Senator LANKFORD. It is everything required. 

Dr. LURIE. It is everything. And, whereas before, there was a lot 

of additional information to collect—— 

Senator LANKFORD. Right, because it was just a two-page form 

before as well. 

Dr. LURIE. Right. 

Senator LANKFORD. So the form is not longer or shorter. The difference is the amount of information required to get in it? 

Dr. LURIE. It is, in fact, shorter, in the sense that there used to 

be 26-odd fields and it is down to 11 fields. 

Senator LANKFORD. Right. 

Dr. LURIE. What we did was we took all of the information that 

was in the attachments and we brought them right into the form. 

So, it is now one-stop shopping essentially. The only thing that you 

now need to attach—and there used to be eight attachments. The 

only thing you now need to attach is the letter from the company. 

Right? And, of course, you have to get that first—and we have al-
273 

ready heard, repeatedly, about the difficulties that doctors sometimes have in securing that, from the companies, for their patients. 

Senator LANKFORD. OK. Talk to me about the internal conversation about acceptable risk. This has been one of the conversations 

to say at what point, as you go through the studies—one, two, and 

three, and the whole process—is the number, the percentage, there, 

of risk. So, help us understand that better. 

Dr. LURIE. Well, certainly there is no way to discuss it, in percentages per se, but what someone can say is that people at the 

FDA understand that risk is something that varies according to the 

severity of the illness and the availability of other successful treatments for that condition. So, when we come up with something that 

is invariably fatal, we treat that differently. If we, instead, are presented with a drug that is to treat allergic rhinitis—right?—that is 

a totally different matter. And, this whole program is about serious 

and life-threatening illnesses for which there are no acceptable 

therapies as an alternative, right? 

So, we are already in that box from the get-go, here, and so, it 

is not a very high bar—and that is expressed, mathematically, as 

the 99-percent approval rate. 

Senator LANKFORD. Right. But, you were discussing, earlier, 

while we are in this box, the difference between the efficacy and 

then the safety issues as well—and talking about the first stage of 

it, then getting on to the second stage, we are getting more and 

more on efficacy and its own effectiveness and trying to evaluate 

that. At what point do you see through this process that someone 

is terminally ill and begins to see some effect that the risk outweighs that? That is pretty much the crux of this conversation. 

Dr. LURIE. Right. 

Senator LANKFORD. When the first level is done and patients 

hear the stories—or people that are not patients hear the 

stories—this seems to be effective, but then there is the pause to 

say, ‘‘We are going to go through multiple other areas.’’ How can 

we quickly get people in there that want to be able to take a higher 

risk knowing that stages two and three have not been done? 

Dr. LURIE. Yes, well, again, the answer is almost always. I 

mean—99 percent—we almost always, in this bucket, are going to 

say that the potential for benefit outweighs the risk. It is in the 

very rare circumstance that we say no. 

I would caution, though, that there is a lot of information that 

is out there about the claimed effectiveness of drugs—some of 

which gets a lot of press attention—and some of that simply is not 

so. Some of it is just not accurate information. And, it ends up creating a lot of noise, which is very difficult for us to refute. 

Senator LANKFORD. What about the double blind studies? Once 

you start going through the process on a terminal illness and you 

deal with those folks that are getting the placebos and you see the 

individuals that are getting the drugs and see a rapid response. 

Dr. LURIE. Right. 

Senator LANKFORD. How do you all deal with the moral issues 

and the ethical issues of leaving those that are getting the placebo—knowing that they are in a terminal status, as opposed to 

trying to shift them over? 

Dr. LURIE. OK. So there—— 
274 

Senator LANKFORD. This is a science versus ethics conversation. 

Dr. LURIE. I understand, absolutely, and so, there are kind of two 

elements to that. First is outside of the FDA, and the other is inside of the FDA. The outside of the FDA is that, in any significant 

randomized controlled trial, with or without a placebo, there is a 

committee that meets on a periodic basis called the Data Safety 

Monitoring Board (DSMB). And, they take a peek at the data, 

maybe every 6 months, to see what is going on, because what you 

would not want—as I think you are concerned about—is that people were in some long-term trial going on for years and years and 

years, and it turns out that back at 6 months you knew that people 

were getting seriously damaged by the drug and it continued for 

21⁄2 years more. Or, that after 6 months, there is such incredible 

evidence of effectiveness that you might as well have stopped right 

there and then, and you did not, and years went by, and people 

were still in the placebo group and the drug was not approved, 

right? Nobody wants that. 

So, these Data Safety Monitoring Boards look in approximately 

every 6 months. They have rules about on which grounds they will 

stop the trial. And, if you meet that threshold, the trial is stopped, 

the blind is broken, and the data is made available. Right? So, that 

is how that works. 

Now, with respect to the FDA, it does not happen especially 

often, but it does happen. There are some drugs that are just 

gangbusters, right? Many of the drugs we have, they help, but 

then, occasionally, you come along with something that just is 

hugely beneficial. And, we have a category for them. We have four 

expedited programs, and one of them is called breakthrough. And, 

if you turn out to have a drug that does that—something that is 

really so remarkable—then you get the breakthrough therapy, and 

with that comes a series of advantages that should get you to market sooner, because the last thing the FDA wants is to have in its 

files some drug that could make a huge difference to patients and 

people not getting it. That would be terrible. 

Senator LANKFORD. OK, so the 6-month time period, obviously, 

for someone who has 1 year or 2 years—or they are feeling profound effects of the drug that is diminishing, whether it is the ability to walk or the ability to be able to speak, whatever it may 

be—the 6-month time period on the double blind to be able to come 

back and evaluate it seems like a long time in those situations. 

Dr. LURIE. No. That is a different matter, Senator. So, the 6 

months is the amount of time—now the trial is done where we 

start talking 6 months. The trial is done. Perhaps, it has been 

stopped by the DSMB, perhaps not. But, the 6 months is from the 

time that the application is presented to the FDA until the time 

at which we make a decision. OK? That is a different matter and 

that does take a certain amount of time. It used to be, when these 

things were not done electronically, we would get literally a roomful of boxes of information, right? Huge amounts of stuff that we 

had to make our way through. And, I should say, parenthetically, 

that the FDA is the only agency in the world who gets that raw 

data, right? There is nobody else in the world who does. 

Senator LANKFORD. But what I am trying to figure out is while 

the study is ongoing—— 
275 

Dr. LURIE. Right. 

Senator LANKFORD. Maybe I misspoke on this earlier. While the 

study is ongoing and you are seeing an effect for those that are receiving the drug and they are receiving benefit—their speech is improving, their muscular function is improving, their organs, or 

whatever it may be—and those that are in the placebo are not. 

Dr. LURIE. Right. 

Senator LANKFORD. And, you see a significant number there—I 

am talking about during the study—the ethical conversation to say, 

‘‘I have people in this study that are terminal,’’ and that you are 

allowing the study to be able to go through, to the end, when you 

see an obvious effect. 

Dr. LURIE. Right. But, what I am trying to explain is that the 

FDA is not involved, in general, at that point, right? This is the 

company who has sponsored the trial—— 

Senator LANKFORD. But, does the FDA require a double blind 

study to be able to go through the process? 

Dr. LURIE. Well, it depends on the nature of the drug, the condition, et cetera, et cetera. But, the point is that there is a control, 

and that control is the DSMB. And, the people who hire the DSMB, 

in effect, are the companies whose drug would come to market. So, 

the conversation that you are worried about—and it is a completely 

reasonable one, and it is what the DSMB is there to address—is 

something that is taking place before the product is presented to 

the FDA. Right? 

Senator LANKFORD. Right. 

Dr. LURIE. It is with the company at that point. 

Senator LANKFORD. Right. 

Dr. LURIE. And, the very concern that you are worried about is 

what the DSMB is for. 

Senator LANKFORD. Well, I am concerned that the FDA has a requirement and that they are trying to fulfill that requirement to 

be able to get the drug to market, but that it may inadvertently 

doom some child or some adult to be stuck in a situation where 

they are receiving the placebo when there is a benefit—— 

Dr. LURIE. No, the FDA wants—— 

Senator LANKFORD. I understand that it is a rare thing to be able 

to see a rapid benefit like—— 

Dr. LURIE. Right. No. The FDA, wants there to be DSMBs. The 

FDA does not want people to go out and collect data for longer than 

is necessary to establish safety and effectiveness. And, if we can 

figure it out even earlier than expected, that is wonderful. We say, 

‘‘stop the trial, please present the data, and come to the FDA.’’ If 

it is that great, there is a fair chance it will wind up in priority 

review. But, we do not want patients stuck in clinical trials that 

are just adding new patients—right?—and not really any meaningful new information about safety and effectiveness. If that is what 

is happening, we want the trial stopped. We want to see the data 

as soon as possible. 

Senator LANKFORD. Mr. Chairman, may I ask one more question 

on this? 

Chairman JOHNSON. Sure. 

Senator LANKFORD. My question is about the toolkit licensing 

that has been proposed out there when you are dealing with a drug 
276 

that has been permitted for a certain organ, but, instead, opening 

it up for a certain type of treatment, for instance, a cancer treatment. So, it is actually a certain cancer. It has been approved for, 

maybe, the stomach, but this is trying to move to another 

area—and I have heard this ongoing conversation. I will tell you, 

I am not a physician, but I wanted to ask about where that is moving in the conversation. 

Dr. LURIE. Senator, I am not prepared to discuss that today, but 

I am happy to look into it further and bring you back some answers. 

Senator LANKFORD. OK. I would be glad to be able to get that, 

because that may broaden out and accelerate some of the process 

as well. 

Dr. LURIE. OK. 

Senator LANKFORD. Thank you, Mr. Chairman. 

Chairman JOHNSON. Thank you, Senator Lankford. 

I think we have spent too much time on this 100 hours, but I 

will point out, on January 4, 2015, you wrote an article in a blog, 

and here is a quote: ‘‘We estimate that physicians will be able to 

complete the finalized version of the form in just 45 minutes as 

compared to the 100 hours listed on the previous form.’’ Again, this 

was in February 2015. 

Dr. LURIE. Right. 

Chairman JOHNSON. It took you 16 months to get that new form 

out there. And, both of those are estimates, right? I mean, was it 

really 100 hours before? 

Dr. LURIE. No. Again—— 

Chairman JOHNSON. And, now it is only 45 minutes? 

Dr. LURIE. The 100 hours was estimating something different, 

right? It was estimating the amount of time to fill out a commercial 

Investigational New Drug (IND), as we call them, the application 

to administer the drug to patients. So, it was estimating something 

different. 

When we went out and developed the estimate for this, I went 

out and I actually found people—physicians, within the Federal 

Government, partly in the FDA—we went to the Centers for Disease Control and Prevention (CDC) and we went to the National 

Institute of Health (NIH). We said, ‘‘Tell us how long it takes.’’ 

Chairman JOHNSON. The bottom line is that for the previous expanded access form, the FDA estimated it took 100 hours to fill it 

out—— 

Dr. LURIE. No, I would not say that—— 

Chairman JOHNSON. Then, it took you 16 months to come up 

with a shorter form. And, now you are saying it takes 45 minutes. 

I am just kind of pointing out the FDA takes a little while to do 

these things. 

Dr. LURIE. Well, Senator, look, I am the guy who put the group 

together, so I am happy to take the criticism home. But, I will say 

this: Under the way our processes work—and I think it is a process 

with which you are familiar—we have to put out a draft guidance, 

which we did in February 2015. We have to wait a certain number 

of days for comments to come in. We have to review those comments. 
277 

Now, what we decided to do this time was not only to just finalize that draft guidance, which is related to this form, we also decided to do more while we were at it. So we did not do one. We 

did three guidances. 

Chairman JOHNSON. That is fine. Again, we are spending too 

much time on this one form—100 hours. I want to get to the real 

crux of the problem here, because I think we are confusing the approval rate versus the ability of a patient like Matt to actually get 

a drug and have the ‘‘Right to Try.’’ So, a 99-percent approval rate 

is one thing, but what is holding up, for example, Matt trying to 

contact a manufacturer 50 times to have access? And, from my 

standpoint, there are three things standing in the way of manufacturers actually taking his phone call and making their drugs available under some kind of expanded access or ‘‘Right to Try.’’ 

First of all it is just the cost of providing it. These are companies. 

They are responsible to shareholders, and as Senator Paul was 

talking about, there is a profit motive that drives innovation and 

drives some of these discoveries. That cannot be minimized. Next, 

it is just the adverse effect and the effect of that—and you spoke 

to that earlier. The other thing is liability protection. So, there is 

an enormous impediment for manufacturers to agree to make these 

drugs available to somebody like Matt. 

I guess I would just like you to speak to all three of those elements again. The cost. Companies develop drugs because, in the 

end, they are reporting to shareholders and they have to make a 

profit. So, it is difficult for companies to just give things away. A 

lot of them do. And, again, it is a $2.6 billion cost, on average, for 

a successful drugs—and that entails the cost of trying to develop 

all of the other drugs that fail. 

So, first of all, talk about the cost. Under the current system, expanded access, what is the allowable rate of reimbursement versus 

what is it actually cost to manufacturers? And, just give us a generalization of that. 

Dr. LURIE. So, one of the three guidances which I was referring 

to is exactly on that point, and what we say in it is that you can 

recover, under expanded access, the direct cost of providing the 

drug. And, the reason for that—and this is the place that we 

reached after taking comment from the public—is that you do not 

want to set it so high that some unscrupulous person might charge 

an arm and a leg to some vulnerable patient, right? So, that was 

the balance that we struck—and it seemed to be acceptable to most 

people. 

Chairman JOHNSON. So, again, companies can get that direct 

cost. 

Dr. LURIE. Yes. 

Chairman JOHNSON. And that would include surgeons, as we are 

hearing from—— 

Dr. LURIE. Yes. 

Chairman JOHNSON. OK. 

Dr. LURIE. They can get the direct cost, correct. 

Chairman JOHNSON. Now talk about just the liability. One of the 

things our bill offers is liability protection, which I do believe people, like Matt, Frank, and people in the audience, would sign a 

stack of liability waivers if they could have access. 
278 

Dr. LURIE. Right. I am afraid you are straying beyond my area 

of expertise at this point. 

Chairman JOHNSON. So, under expanded access, do you know one 

way or the other whether there is liability protection? 

Dr. LURIE. I cannot speak to that, Senator. 

Chairman JOHNSON. And, then speak again to the adverse impact—or the adverse effect—and how that really is going to weigh 

into a manufacturer’s decision of whether or not they want to take 

that call from Matt and make a drug available. 

Dr. LURIE. Right. Well, we are hoping that they pay attention to 

the study that we published, because I think it is immensely reassuring. I mean, 2 out of 1,000 drugs were put on clinical hold—and 

only temporarily. I think from that, if I were a manufacturer, I 

would say, ‘‘Well, that is really pretty reassuring.’’ And, quite honestly, if I were a manufacturer, I would want to know about the 

adverse effects that my drugs might cause sooner rather than later. 

I would not want to have my drug on the market because some adverse effect was ignored during expanded access—only to have it 

recur, where you might face liability when the drug is actually on 

the market. 

But, Senator, we see some other reasons why the companies hold 

back—and I think you have heard a lot of testimony about how frequently that happens. And, I pointed out how one company has 

turned down, in 6 months, more than the FDA turned down in 5 

years for all drugs. 

Chairman JOHNSON. But, tell me why. Do you have any idea why 

that one company turned—was it because of lack of liability protection? Was it because of the concern about adverse effect? Was it because the direct cost really did not reimburse them properly? Do 

you have any idea why they turned them down? 

Dr. LURIE. Sorry. Why the company—— 

Chairman JOHNSON. Correct. Do you have any idea what the rationale was? 

Dr. LURIE. Why do companies turn them down? 

Chairman JOHNSON. Yes. I mentioned three reasons. Do you 

have additional—— 

Dr. LURIE. I do. And, one is—and this sound totally banal, but 

it is true—there may not be enough drug around, OK? And, the 

companies are not in the business of making massive quantities of 

drugs for products that may never be approved. And, remember 

that lots of these expanded access products will never be approved, 

right? 

Chairman JOHNSON. Some of these drugs are extremely expensive to manufacture, correct? 

Dr. LURIE. Some of them are. And, you would not want to be 

making excess amounts of those if your product was never going 

to be approved. So, what they tend to do is to make an amount, 

maybe a little bit of excess, that will support the clinical trial. And, 

that is the second part of my answer. 

The companies agree with us that the best way to get safe and 

effective drugs to people is through the clinical trial process—and 

they do not want to see that undermined in any way. And, we 

agree with them because we think, in the end, that is how you do 

it. Then, you are sure. And, it is not one patient at a time, as com-
279 

pelling as one patient is. There are thousands of patients behind 

them who we also need to think about. And, for them, it is the clinical trial process that will be lifesaving in some cases. 

Chairman JOHNSON. So, let me finish out, just kind of going back 

to the question that Senator Lankford was talking about in regard 

to breakthrough drugs. Once again, here is the FDA making decisions for people—and, every drug is different and every situation 

is different. But, again, I just put myself in the position of a parent 

with a child, where you see over the years, through a clinical trial, 

that a drug, like the drug that was just approved for DMD is having a positive impact. And, your only access is to do a clinical trial, 

thinking that your child is maybe getting just saline. There has to 

be some way to give those parents the right to just, actually, make 

sure they get the drug. Do you understand that? 

Dr. LURIE. I do, Senator. 

Chairman JOHNSON. When it all comes right down to it, going 

back to the assemblyman from California, talking about, you have 

the right to die, why not the ‘‘Right to Try.’’ There is just something, in terms of the FDA making these decisions for parents and 

patients, that we have to come to grips with to let individuals 

make that decision—rather than have the FDA make it for them. 

At a certain point—and, again, from my standpoint, we are talking 

about once you have gone through Phase I, because there is a certain level of safety that has been agreed to. Again, you always are 

assessing a drug for safety even way past approval. You are always 

looking for that. I guess just respond to that. 

Dr. LURIE. Well, it is hard to say that the FDA is making those 

decisions for people when we approve 99 percent of our applications. I mean, to me, if I am looking at a process—— 

Chairman JOHNSON. But, again, that is not talking about all of 

the impediments for people even in applying. 

Dr. LURIE. Right, but that is not us, sir. 

Chairman JOHNSON. Well, it is the adverse impact. It is the approval process. It is all of those things. You are a part of that whole 

process. 

Dr. LURIE. I think we do need to keep the approval process and 

the expanded access process, separate in this conversation. And, 

there are efforts that Congress is discussing about the approval 

process, but that seems, to me, a different matter here. And, we 

should not really mix them together. 

With regard to expanded access, we do understand how patients 

feel. And, it is for that reason—and, taking into account risk and 

benefit in their particular context—how desperate they can be— 

that is the reason they practically all get approved. 

Chairman JOHNSON. So, we have 31 States— maybe with California passing it, 32 States—with these ‘‘Right-to-Try’’ laws on the 

books. And, all we are trying to do is get the Federal Government 

to kind of stay out of the way so that those ‘‘Right-to-Try’’ laws will 

actually work in the States. But, you cannot tell me one way or the 

other whether the FDA is going to allow those States’ ‘‘Right-toTry’’ laws to work. 

Dr. LURIE. Well, again, the Agency does not have a position on 

any of those bills or, for that matter, the Federal one. But, I will 

say this: If I were looking at a process—a multi-step process with 
280 

multiple collaborators and partners—industry, the doctor, the FDA, 

and so on—and I looked at a part of that process that approved 99 

percent of applications—that improved many of those that we got 

and did so quickly, I probably would not be looking at that part as 

the part to reform. 

Chairman JOHNSON. Thank you, Dr. Lurie. 

Dr. LURIE. Thank you. 

Chairman JOHNSON. The hearing record will remain open for 15 

days until October 7, at 5 p.m., for the submission of statements 

and questions for the record. This hearing is adjourned. 

[Whereupon, at 12:22 p.m., the Committee was adjourned.] 
(281) 

A P P E N D I X 
282 

Statement of Ranking Member Tom Carper 

"Exploring a Right to Try for Terminally Ill Patients" 

September 22,2016 

Thank you, Mr. Chairman, for calling this hearing today. I appreciate your willingness to 

continue a conversation about an important issue that is critical for Americans seeking access to 

potentially lifesaving treatments. I also want to thank you and your staff for the ongoing work 

that we are engaged in to try and move the ball forward and find ways to help patients gain 

access to experimental therapies, including through a forthcoming GAO report on these issues. I 

also want to thank our witnesses, especially Representative Neely, Mr. Matthew Bellina, Mr. 

Richard Garr, and Mr. Andrew McFadyen for their willingness to share their personal stories 

with us. 

Before I begin my formal statement I would just like to mention my appreciation for the 

Chairman sharing this video. !look forward to learning more about this physician's experience. 

My understanding is that in what would seem to be similar situations, the U.S. Food and Drug 

Administration (FDA) has approved over 99 percent of patient applications for expanded access 

to these new experimental treatments. In fact, I understand the FDA has even granted drug 

approvals based solely on expanded access data. The FDA is, by law, precluded from discussing 

the details of any drug under review, but if the doctor was with us today, I would ask him why he 

did not appear to use the expanded access program which has worked quickly and efficiently for 

so many patients and their doctors. With that in mind I would like to ask unanimous consent that 

we place an FDA fact sheet on expanded access along with the recently updated application form 

in the record. 

Today, we will have an opportunity to hear from the FDA, state representatives, patients, their 

loved ones, and other advocates on ways we could improve access to experimental medical 

treatments. These individuals and their families have faced some of the most difficult and painful 

challenges anyone could face. They deserve to be heard, and they deserve better access to 

experimental treatments. We will also have an opportunity today to review the Chairman's 

Legislation, S. 2912 the Trickett Wendler Right to Try Act. I appreciate the intent of Chairman 

Johnson's bill, and certainly support expanding access to experimental therapies to terminally ill 

patients. 

We must keep in mind, however, that there is already what I understand to be an effective 

framework in place at the FDA that gives patients access to experimental drugs while those 

drugs are still being tested. The agency has given an extraordinary level of attention to the 

requests of patients with life-threatening conditions. In fact, I'm told it has approved more than 

99 percent of requests for emergency treatments between 2010 and 2015. The agency has also 

taken constructive steps to greatly simplify its application process and further improve and 

streamline patients' access to experimental treatments. 

Despite the high approval rates and ongoing reforms, I understand that the FDA believes more 

can be done and is continuing to work to improve patient access to experimental treatments. I 

hope to learn more about those steps today, as well as some additional ideas for how to ensure 
283 

that all patients in need have the information and resources necessary to access experimental 

medicines. 

For terminally ill patients and their loved ones, safe and effective treatments cannot come 

quickly enough. That is why we need to do everything we can to give patients, doctors, and the 

companies that make these drugs the tools they need to participate in clinical trials, utilize the 

FDA's expanded access programs, and develop new treatments as safely, effectively, and 

quickly as possible. I hope this committee can help with those efforts and work with patients, 

health care providers, the pharmaceutical industry, and the FDA to ensure that all patients and 

their families can access safe and effective treatments as quickly as possible. 

I want to close by thanking the witnesses and their families again for their willingness to share 

their stories and put forward possible solutions to these challenging issues. 
284 

Statement of Matthew Bellina 

HSGAC Hearing- September 22, 2016 

As a 32 year old father, U.S. Veteran, and terminally ill ALS patient, I wanted to clear up some 

misconceptions about S. 2912 and HR 3012-the Right to Try Acts 

I should begin by clarifying a key point. No one who supports the federal Right to Try Acts or the 

state laws they protect wants to undermine the FDA or relax the standards that must be met for drug 

to be officially approved by the FDA. We simply believe that we can do better at getting promising 

treatments to sick and dying Americans. 

A recent GAO report found that the pace of scientific discovery is stifled by an overly burdensome 

regulatory environment in the FDA's clinical trial protocol. ALS is a perfect illustration. There are 37 

known ALS genetic mutations that make up less than 10% of all cases. The other 90% of ALS 

patients are suffering from a similar disease (or diseases) of unspecified cause. Under the current 

regulatory environment, all ALS patients are put into the same clinical trial cohorts in the hopes that 

one drug might show efficacy in the overall patient population. This is bad science and can never be 

successful. 

Right to Try laws will let doctors look at individual patient biomarkers and work with pharmaceutical 

companies to use known compounds that target a patient's specific disease profile. This is the future 

of medicine--and we have the technology, just not the regulations, to allow us to do this now. I 

cannot speak directly for them, but I surmise this is why the ALS Association recently endorsed S. 

2912. 

I have heard the argument that this legislation would subject patients to risk and they would have no 

legal recourse if things go wrong. I have heard the only thing worse than a terminal illness is being 

terminally ill and suffering a major complication as a guinea pig in an experimental treatment that 

you had to pay for. 

Without any intended insult, I do not believe it is the role of interest groups or bioethicists who have 

never met me to dictate how I should find value in my remaining days. If some believe that living 

without hope is superior to living with the risk of side effects that is their personal business. 

My motor neurons are dying and without treatment I will suffocate under the weight of my own 

chest. I am willing to make informed choices with my doctor, based on the individual nature of my 

disease. Furthermore, any compound that would quality as a Right to Try drug would already have 

passed safety trials and be in an active FDA-approved Phase 2 or Phase 3 trial. In other words, the 

FDA has already deemed the compound worth the risk of further exploration. 

Why shouldn't I be given the same right as the limited number of patients lucky enough to get into 

clinical trials? 

I have also heard the argument that the FDA's current compassionate use program already provides 

patients with the opportunity to try investigational drugs. But this program is severely flawed. The 
285 

FDA itself has acknowledged these flaws by attempting to streamline the application process and 

proposing a new office within the agency to help dying people navigate its bureaucracy. 

As long as bureaucrats are making the decisions about which terminal patients are privileged enough 

to have access to investigational treatments, the academic and scientific integrity of 

biopharmaceutical research will be inhibited, in the best-case scenario. In the worst-case scenario, we 

will continue to repeat the same sample bias, which has failed to cure heterogeneous diseases for 

over 60 years. 

I have heard the argument that bypassing the oversight of the FDA is not in the best interest of 

patients or public health. This is a straw man argument. No one is asking to bypass FDA oversight. 

Lawmakers must realize that only drugs active in Phase 2 or Phase 3 trials will qualify as Right to 

Try drugs. The FDA will still have control over what drugs can be bought and sold in the United 

States. And because the availability of drugs under Right to Try depends on the FDA trail process, 

the "Gold Standard" remains completely intact. 

The greatest weakness of these bills is that many pharmaceutical companies may choose not to 

participate. If that happens then we have missed a great opportunity, but no one will be overtly 

harmed. On the other hand, the risk of not passing these bills is that a good drug may languish for I 0-

14 years in the FDA pipeline and countless Americans will die. Their lives will end without the 

chance to exercise their Constitutional freedom to make choices regarding their life, liberty, and their 

own pursuit of happiness. 
286 

Testimony of the Honorable Ian C. Calderon 

Majority Leader 

California State Assembly 

Before the 

United States Senate 

Committee on Homeland Security and Governmental Affairs 

"Exploring a Right to Try for Terminally Ill Patients" 

September 22,2016 
287 

Thank you Chairman Johnson, Ranking Member Carper, and Members of the 

Committee for inviting me here today. I am honored to testify before you about 

Right to Try for terminally ill patients. 

As Majority Leader of the California State Assembly, I am fortunate to work on a variety of 

public policy issues every year. This year alone I've sent bills to the Governor dealing with 

issues ranging from ensuring that financial literacy is part ofthe high school curriculum, to 

setting minimum fines for piracy violations. While each bill I work on is a piece of policy I 

believe strongly in, my work on Right to Try legislation over the last two years has truly given 

me purpose as an elected official. The fight to allow terminally ill patients to seek 

investigational drugs and treatments not yet approved by the FDA is something I'm immensely 

proud to be a part of in California, and I thank you for giving me the opportunity to talk about it 

today. 

In January of2015, much of the policy conversations in California centered around "Death with 

Dignity." If you recall, this was mere months after Brittany Maynard, the young woman 

diagnosed with brain cancer, had moved from California to Oregon, in order to utilize Oregon's 

Death with Dignity law. While researching Oregon's law and its possible application in 

California, it struck me that this conversation needed to include policy prescriptions to make it 

easier for these terminally ill patients to fight to save or extend their lives as well. It was then 

that I came across the Right to Try movement, and subsequently introduced Assembly Bill 159. 

For me, Right to Try was a logical companion to Death with Dignity. I never saw the two issues 

as incompatible. I didn't want to limit the options for those diagnosed with a terminal illness, to 
288 

only death, albeit a more controlled one. I felt strongly that if we were going to pass Death with 

Dignity, and thus make it easier for terminally ill patients to die in California, that we should also 

make it easier for these terminally ill patients to fight to live, by giving them access to potentially 

life-saving drugs and treatments, that have been deemed safe, but not yet approved by the FDA. 

As the first iteration of California's Right to Try legislation made its way through the legislative 

process, I had the privilege of meeting David Huntley. David was a Professor Emeritus at San 

Diego State University, an accomplished ironman triathlete, and an obviously loved husband and 

father. David was also diagnosed with ALS, more commonly known as Lou Gehrig's Disease. 

It's a death sentence given our current lack of understanding of the disease, but there are ways to 

combat the speed at which it progresses, and the pain it causes. Shortly after his diagnosis, David 

learned that there was a promising new drug called GM604, that was still in the clinical trial 

process at the FDA, and thus had not yet been approved. He sought access to this drug, but was 

denied. So David spent the latter part of his life fighting to give patients like himself a chance. 

David agreed to fly up to Sacramento in April of last year to testify with me before the California 

Assembly Health Committee. This was the first committee hearing on Right to Try in 

California. David's testimony and clear understanding of the pitfalls of the current experimental 

drug access paradigm was instrumental in getting us past that first legislative hurdle. 

It was evident that David was in a tremendous amount of pain, yet he was determined that he be 

there to help Right to Try legislation pass in his home state. Just three months after testifying, on 

July 4'h, 2015, David Huntley succumbed to ALS and passed away. He came to Sacramento to 

testifY, for a measure he knew would be too late to help himself, but to ensure that future 
289 

tenninally ill patients have the access to potentially life-saving medication he had been denied. 

That kind of selflessness is rare, and l 'II never forget his dedication. 

With David's help, Right to Try passed the Assembly Health Committee, but it still faced intense 

scrutiny from five more Committees in the Assembly and Senate. Though this was only last 

year, it was early in the Right to Try movement. The bill went through a rigorous public hearing 

process, where we sought to improve upon the Right to Try legislation that had been introduced 

in other states. Each Committee, in concert with the myriad of stakeholder groups, and in 

deference to concerns that felt unique to California, included amendments to the legislation. 

Throughout the Committee process we worked on, and eventually added, several amendments to 

alleviate concerns about having proper oversight patient protections. We added Institutional 

Review Board Oversight of a physician's recommendation, in order to ensure that patients are 

fully aware of the potential side-effects of any investigational drugs they may consume. We also 

added a requirement that a consulting physician confinn the primary physicians' diagnosis that 

the patient is terminally ill, and inserted reporting requirements to the California Department of 

Public Health, to further increase oversight. And, similar to the difference I see in Senator 

Johnson's Right to Try bill versus the House's version, we clarified that the legislation would not 

create a private cause of action against the prescribing physician or drug manufacturer this was 

instrumental in removing the opposition of the California Medical Association. 

While we weren't able to completely remove all opposition to the California's Right to Try bill, 

through the public hearing process we did work to address many of their concerns, without 

compromising the strong intent of my bill. When my Right to Try bill reached the Governor's 
290 

desk last year, I was satisfied that due to its strong patient protections and robust oversight 

requirements, it was one of the most comprehensive versions of Right to Try legislation in the 

country. 

The governor vetoed my bill. In his veto message, he acknowledged that the FDA was in the 

process of streamlining its Expanded Access application, and wanted to grant the agency the 

time to do so, with the hope that this new application would make a state process unnecessary. 

As 31 other states have passed Right to Try legislation, I'm happy to have been a part of the 

impetus that spurred the FDA to streamline the application. However, these new regulations, 

announced in June ofthis year, only deal with streamlining the physician's portion of the 

application. This is an improvement, but the new process does nothing to shorten the 

manufacturer's portion and the data required by the application or reduce the 30 days the FDA 

has to decide. According to statistics furnished by the FDA, roughly 1,000 terminally ill patients 

make it through the costly and cumbersome application process each year. Considering the fact 

that 564,000 Americans are expected to die from cancer alone this year, the small number of 

people navigating the FDA's Expanded Use program speaks to the program's failure to actually 

help terminally ill patients obtain access to life saving treatment. These patients do not have the 

luxury of waiting for an onerous, bureaucratic process. This is one of the chief reasons Right to 

Try Legislation is so important. In the midst of a battle with a life-threatening illness, it is much 

easier for a patient to deal with their own doctor than a large and impersonal government agency. 

At the beginning of this year, I re-introduced Right to Try legislation in California. Fortunately, 

with all of the protections added via last year's comprehensive public hearing process, Assembly 
291 

Bill 1668 had a much smoother path through the State Assembly and Senate. It now sits on the 

Governor's desk, and I'm hopeful will merit his signature, adding California as the 32"d state to 

enact Right to Try legislation. 

Mr. Chairman, members of the Committee, thank you for giving me the opportunity to share my 

effort to bring Right to Try to California. I applaud any effort at the Federal level to do the same 

nationwide. I hope the federal government doesn't stop there. We need federal legislation that 

expedites the FDA's drug approval process. It should not take 10 to 15 years to approve new, 

life-saving treatments. In the meantime, I commend the federal effort to encourage states to 

essentially adopt methods to work around the FDA. 

Right to try, at its core, is very simple and speaks to a basic human right. If your parent, your 

child, or even you are faced with a terminal illness, there should be a process in place for you to 

seek potentially life-saving treatments, and the government should not impede that. Thank you 

very much for your time. 
292 

Why Patients Need the Right to Try Dr. Jim Neely - State Representative -Missouri's 8th District 

Mr. Chairman, members of the committee, my name is Jim Neely. I'm a physician and State 

Representative from Cameron, Missouri. I'm here to go on the record in support of this bill 

because terminally-ill patients don't have time to wait for the FDA to approve investigational 

treatments. 

I've been practicing medicine for over 30 years. Over that time, I've seen patients with medical 

conditions and issues oflife that have been very challenging to deal with; from cancer to 

multiple sclerosis. 

I remember treating my first AIDs patient back in 1985 in Florida. After the examination, I 

walked out of the room with very little idea of how to help him. I regrouped with other 

physicians, and we agreed, without access to an experimental treatment, he was completely 

hopeless. 

There were clinical trials at the time, but he wasn't eligible. We needed more options. The FDA 

didn't approve the first effective antiretroviral for AIDs until the following year. It was too late. 

Disincentives for Compassionate Use 

Throughout my medical career, I've been troubled by the laws that restrict suffering patients' 

access to investigational treatments. As a physician, my practice is guided by evidence, so I 
293 

understand the importance of our clinical trial system; however, terminally-ill patients deserve 

the option to try investigational treatments after they have exhausted all approved treatment 

options and are no longer eligible for clinical trials, 

As I began considering this issue as a State legislator, my daughter Kristina was diagnosed with 

Stage 4 colon cancer. She had four children at the time, and was carrying her fifth, which 

severely limited her eligibility for clinical trials. From a research perspective, I understand the 

importance of studying a uniform group of patients, but there has to be room for compassion for 

patients, like my daughter. 

Before she passed away, Kristina was adamant that her right to try treatments "shouldn't be up to 

somebody that has no involvement in my care." I believe this bill goes a long way toward giving 

more options to terminally-ill patients and their doctors. 

Restricted Access Harms Indigent Patients 

A friend of mine, Ross Nichols, came to testify in support of the Right to Try bill we passed in 

Missouri. At the time, he was receiving treatment at MD Anderson for glioblastoma, the most 

common and aggressive form of brain cancer. Ross knew that the experimental treatments he 

received were unlikely to save to his life, but he still sought to enroll in clinical trials, c;cplnininl!, 

"my number one job right now is being a dad, and I'll do whatever I can do to try to extend that." 

Ross told the committee that he was testifying for the bill because he wanted people in Missouri 
294 

to have access to the same treatments that were available to him at the research institutions he 

could afford to travel to. l-Ie was right. 

Many people fighting for their life, cannot afford to spend what-could-be their final months 

traveling across the country in order to receive investigational treatments. I'm glad Ross was 

able to travel to receive treatment that gave him hope, but he shouldn't have had to. Ross passed 

away in February of2015. I'm glad his hope for other patients lives on with this bill. 

Restricted Access Strains the Doctor-Patient Relationship 

Rick Suozzi, father of the late Kim Suozzi, also came to testify in support of our right to try bill 

in Missouri. His daughter was diagnosed with glioblastoma at age 21, during her final semester 

at Truman State University. Kim knew her diagnosis was a death sentence, but she went to 

extraordinary lengths for a small chance to survive. She traveled to the top cancer research 

institutions - Dana Farber, UCLA, MD Anderson, and Duke- just to participate in clinical trials 

that gave her a glimmer of hope. 

Kim enrolled in three trials in the last six months of her life. When she was no longer eligible for 

clinical trials, she lied to research doctors about her treatment history in order to make herself 

eligible. Can any of us blame her? 

Thank you for giving me the opportunity to share these stories. I believe government should 

create opportunities for people to care for each other, not erect and maintain barriers. This bill 
295 

knocks down some of the major barriers to care that make life even more difficult for terminallyill patients. With that, I'd be happy to take any questions. 
296 

In Support ofS. 2912 

Richard Garr 

Former President and Chief Executive Officer, Neuralstem, Inc. 

US Senate Committee on Homeland Security & Governmental Affairs 

Hearing: Exploring a Right to Try for Terminally Ill Patients 

September 22, 2016 

I would like to thank the committee for this opportunity to testify in support of S 2912, 

known as the Trickett Wendler Right to Try Act. As President & CEO of a biopharmaceutical 

company developing treatments for currently incurable diseases; as a member of the 

advisory board that helped craft the model right to try act which has been making it's way 

through the states; and as the father of a son diagnosed with a grapefruit sized brain tumor 

at age 4; I have been involved in the scientific, FDA regulatory, business, legislative and 

patient advocacy arenas germane to this issue for over two decades. S. 2912 is a good bill 

that will provide hope and comfort to many patients diagnosed with fatal diseases; and it 

will accelerate the effort to find cures for currently incurable diseases. 

It is not without its controversies and issues, but I believe many of the criticisms of the bill 

are the result of misinformation and lack of understanding of how the bill actually will 

work. I would like to spend my limited time here today setting the record straight and 

answering these criticisms. 

An often heard criticism is that the bill allows unsafe medicines to be foisted on an 

unsuspecting public. Nothing could be further from the truth. This bill, like all of the state 

passed bills that have preceded it, relies heavily on the proven safety track record of the 

FDA. No treatment may be administered under this bill unless it has already successfully 

passed through an FDA safety trial; AND is continuing in the FDA approval process into 

later stage trials. This insures that there is a continuing evaluation of the safety of any 

treatment administered under a right to try act. If a company, for any reason, safety or 

otherwise pulls a drug from the FDA que it is no longer allowed to be administered under 

the act. I would note that this is not a protection afforded to the public with respect to 

approved drugs. 

I will also point out here that treatments for fatal diseases are obviously extremely difficult 

to develop. The failure rate is obviously extremely high and so no company enters into such 

an undertaking lightly. Even in small biotech companies such as Neuralstem, which I had 

the honor to help found and run for 15 years, we spent tens of millions of dollars over a 

decade to get our ALS product into the clinic. The body of science required, and 

sophistication and volume of pre clinical safety data required to simply get into an FDA 

approved trial is an enormous undertaking. The point is, in addition to a successful phase 
297 

one safety trial, there is a large body of pre clinical safety data and manufacturing process 

purity data behind all of these treatments, by definition; no exceptions. I would also point 

out that the FDA often continues to request continuing non human safety testing as a drug 

moves through the approval process and new data becomes available. These are heavily 

vetted and continually investigated treatments being made available by the act. 

I would also like to debunk the myth that this is somehow an "anti FDA" bill. Again, nothing 

could be further from the truth. As just explained, the bill's heart is the safety net that 

continuing FDA oversight provides. An oversight by the way, that is universally 

acknowledged as the gold standard for the world. Even proponents of the Right to Try 

movement such as the Goldwater Institute, who might believe that the right to try is based 

on a Constitutional principle, and might disagree with the idea of Federal pre emption have 

insisted on this FDA oversight principle on safety. This is not an anti FDA effort. 

I would like to address the argument I have heard that this act gives false hope to patients, 

promising cures. As I mentioned I have been involved in the ALS and brain tumor patient 

community for a long time; as well as patient and caregiver communities in other currently 

incurable but not fatal diseases. The biotech and pharmaceutical industry is meticulous 

about educating patients as to the experimental nature of their treatments in the trial 

stages. While we are always hopeful that we are on to something substantial, patients are 

always informed that they are helping to accelerate research, and not being promised a 

cure. I will also tell you that these diseases are devastating emotionally to patients and 

their caregivers. They often feel a sense of hopelessness and despair. In ALS, some make 

their peace with their fate and focus on their remaining time. But many tell you they would 

like to "go down fighting" and being part of experimental research, whether in a clinical 

trial setting or through a right to try compassionate use setting, lends an additional sense of 

purpose to their lives. Having hope for many, is an essential element to improving their 

quality of life, even if it is a small hope. Patients and caregivers alike know that even every 

failure brings us closer to an actual cure and their doctors will tell you that that can add 

great comfort and some sense of control to their lives as they struggle through their illness. 

The fact that a doctor must administer these treatments ensures that patients have this 

information before undertaking any treatment. So yes, this is a choice, but it is an informed 

choice. This is a right to try act, not a right to cure act and all patients will understand this 

as a result of the mechanisms built into this bill. 

I would like to address two areas more related to the "business side" of Right to Try. Yes, 

companies need to be able to charge for the treatment, and they should be free to set the 

cost. Almost all new experimental treatments for fatal diseases are going to be modern 

medicines; cell and/or gene therapies, monoclonal antibodies etc. The ability to apply 

resources to provide treatments while simultaneously conducting clinical trials will vary 

from company to company. There can be no "one size fits all" cost formula that would be 

either fare or productive. Only a company knows its true opportunity costs in such a 

situation. Indeed, there is nothing in any of the state bills, and of course nothing in this 

federal bill, that requires a company to make its treatment available under right to try. 

This too must be decided by the company itself. 
298 

I have heard the criticism that actually carrying this out is simply "too hard". That all of the 

unresolved issues around insurance reimbursement and liability, both professional and 

product, added to a fear of "rationing" because of scant availability and a host of others 

make this unworkable. It is true that all of these issues must be addressed, but it also true 

that we have these exact same issues with respect to approved drugs; and that in fact we 

are an industry completely based upon the proposition that all of these issues are 

addressable. There are people in the applicable chairs throughout the space who work on 

these issues all day every day with respect to approved drugs. This will be no different. 

Not every resolution will be perfect, and not everyone will be happy with how these issues 

are resolved, but that is also true with approved drugs; and just as with approved drugs, all 

of these issues will get resolved. 

Finally, I have heard it said that there are already dozens of states that have passed these 

laws and yet no one is being treated. I can tell you wearing my industry hat that no 

company will feel comfortable acting under these state laws, until the protections afforded 

companies under this Federal law are enacted. This Bill is essential to unlocking the 

promise of all of the Right to Try acts. 
299 

Congressional Hearing Written Submission 

Exploring a Right to Try for Terminally Ill Patients 

Andrew McFadyen I The Isaac Foundation 

September 22, 2016 
300 

Congn."~~iona! Hearing Testimony I Exploring a Right to Try for Terminally lll I September 22, 20161 The !s~ac Foundatlon 

is an organization based in 

Canada that has dedicated itself to Hnding a cure !or a rare and devastating 

disease called Mucopolysaccharidosis, or MPS. Our work pushes 

international boundaries, with the bulk of our advocacy and patient support 

taking place in Canada and the United Stares. This is an organization that is 

very dear to me, because it is named after my son my hero, and the bravest 

person I know- Isaac Mcfadyen, who sufrers from MPS Type VL 

"\Vhen Isaac was diagnosed at the age of 18 months, we were told that he was 

going to live a life of pain and suffering, and that we would endure many 

years of heartache and heartbreak. Throughout the course of his life, we were 

told that Isaac was sure to suffer from heart and airway disease, progressive 

stiffening of his bones and joints requiring hip and knee replacements and other orthopaedic surgeries, 

corneal clouding, shortened stature, and a severely shortened lifespan. Essentially, every bone, muscle, 

organ, and tissue in his body would be ravaged by this disease until he eventually succumbed to the 

condition, probably in his early to late teens. 

During the past decade he's battled- we've battled to stave off the inevitable. And we've been 

lucky. In 2006, after a lot of work and determination, we were able to bring a new !He-prolonging 

treatment to Canada- an enzyme replacement therapy that was approved by the FDA but nor by 

Health Canada- to Hght his disease. Isaac is now 12 years old, and the 12 that we see today is very 

different than the 12 we were told to prepare for. 

After our success bringing Isaac's treatment to Canada, 

other families began contacting our organization so that we 

could help them obtain access to rare disease medications, 

provide advocacy and support, and walk alongside them 

throughout their journey. At the time, we knew of only 3 

children in Canada Hghting this disease, and Isaac gaining 

access to treatment prior to its approval opened the door for 

the other children to get the help they needed as welL After 

another 11 patients were diagnosed, we worked to ensure 

that all14 patients in Canada battling MPS VI were 

receiving access to their life-sustaining medication prior to 

approval from Health Canada. 

I'm proud to say that we've 

never been unsuccessful 

gaining access to rare 

disease treatments for 

children in Canada. and our 

work directly with 

pharmaceutical companies is 

helping patients see similar 

results in the United States 

These successes brought many more families our way families battling other forms ofMPS, battling 

other diseases - from Duchenne Muscular Dystrophy, to Hatten Disease, to Gaucher Disease, to rare 

paediatric cancers. Our mission to Hnd a cure fi:1r our son became a multi-faceted mission - a mission 
301 

Congressional Hearing Testimony I Explori11g a Right to Try for Terminally Ill Parienrs I September 22, 2016 I The Isaac Foundation 

that crossed borders and crossed disease families. It became a mission to help those who were 

suffering &om any rare disease and in need, and we've dedicated ourselves to that mission ever since. 

Today, I'm proud to say that we've never been unsuccessful gaining access to rare disease trearments 

for children in Canada, and our work directly with pharmaceutical companies is helping patients see 

similar results for countless children in the United States. We've achieved this success in part because I 

understand the world that our families are living in, and I understand the unbearable burden that a 

potentially terminal diagnosis brings. I understand because I live each and every day facing the 

mortality of my son. I understand because after 10 years, I still wake up every night and check to be 

sure that my son is still breathing, crippled by the fear that one day I'll walk in and he won't be. I 

understand because I've walked this lonely road, searching for Hope when all Hope seemed lost. I've 

been there - I'm still there - and I continue to work tirelessly to find a cure for him before the clock 

runs out. 

It's because I've been there that I can see the appeal that Right to Try legislation brings to those who 

have nowhere else to turn. The Goldwater Institute has done a marvellous job of promoting Right to 

Try laws as being the last chance for people to extend their lives. Very pointedly, Goldwater claims 

that "Right To Try laws help patients get immediate access to the medical treatments they need before 

it's too late," and have characterized Right to Try laws as legislation that "restores life-saving hope 

back to those who've lost it."1 

This utopian vision of access 

to medications for millions of 

Americans who desperately 

need them is laudable. 

However. the cruel reality 

with Right to Try legislation is 

that it will not grant patients 

the immediate access to 

treatments they desperately 

need. 

This utopian vision of access to medications for millions of 

Americans who desperately need them is laudable. The tagline 

that my organization uses is "Love, Laughter, and Hope." Love 

and Laughter because this is what my son and our families give 

me each and every day. Hope because sometimes that is all you 

have left. So I understand Hope, and the pull for families to seek 

that Hope wherever they can find it. 

However, the cruel reality with Right to Try legislation is that it 

will not grant patients the immediate access to treatments they 

desperately need. Although various forms of Right to Try laws 

have been passed in 31 states, there continues to be no concrete evidence of a patient ever receiving a 

life-saving or life-sustaining medication under Right to Try legislation when they otherwise wouldn't 

have received it under the existing FDA program. This equates to over 183 million Americans 

currently living within the boundaries governed with Right to Try laws. Why then, with 57% of 

Americans having, as Goldwater claims, "immediate access to medical treatments they need", do we 

1 "About Right to Try- Give Terminal Patients the Right to Try." 2015. 15 Sep. 2016 <http;//rigNtotry~org/a_bout,rigN­

!Q:tryL> 
302 

Congressional Hearing Testimony I Exploring a Right to Try for Terminally Ill Patient> I September 22, 2016! The Isaac Foundation 

still have no data or evidence to prove these state laws are actually doing what they purport to do? 

The answer is simple -they aren't. 

Indeed, legislation does not guarantee access to investigational therapies for those in need- it never 

has. Right to Try legislation provides nothing to patients except the "right not to be barred from 

seeking access to experimental product~."2 Legislation has, however, created a misguided belief 

among vulnerable patients that the help they have been desperately searching for has arrived. Right to 

Try is a misnomer, implying an entitlement to patients: "If a person asks, someone or some entiry has 

a duty to provide."' 

A more apt tide would be "Right to Ask", because this is the only entitlement Right to Try legislation 

provides patients. This right to ask has been given to patients in need since 1987 through the FDA's 

Expanded Access Program. For both the FDA program and Right to Try laws, pharmaceutical 

companies are under no obligation to make their investigational drugs available to patients.' Thus, 

investigating what disincentives prevent companies from deciding to make their drugs available and 

what incentives could be put in place to change these decisions would be a more fruitful approach 

than legislating a theoretical "Right to Try". 

Some States' Right to Try legislation also have the potential to create unequal access to medications 

for patients. Under the FDA's current Expanded Access program, pharmaceutical companies are only 

allowed to charge patients direct costs and select indirect costs associated with providing access to 

patients. Such charges must be approved by the FDA and serve to protect patients from being taken 

advantage of by pharmaceutical companies.' Most often, companies chose not to charge patients. 

Under State Right to Try legislation, companies can charge patients as they see fit, except in Texas, 

where the law requires that companies provide their investigational drugs for free. This would create 

a situation in which vulnerable patients may pay exorbitant prices for unproven therapies, acting out 

of desperation. Furthermore, patients trying to access drugs under Right to Try laws may find 

themselves in the precarious position oflosing access to home health care, hospice care, or even 

insurance.6 

2 Bateman-House, Alison et al. "Right-to-Try Laws: Hope, Hype, and Unintended Consequences." Annals of internal 

medicine 163.10 (2015): 796-797. 

3 Bateman-House, Alison et al. "Right-to-Try Laws: Hope, Hype, and Unintended Consequences." Annals of internal 

medicine 163.10 (2015): 796-797. 

4 Rubin, Rita. "Experts critical of America's right-to-try drug laws." The Lancet 386.10001 (2015): 1325-1326. 

5 2016 US Government Publishing Office, 2016, Part 312.8 <bJtps:/l_wwwcgl:>o-99Yi> 

6 Bateman-House, Alison eta!. "Right-to-Try Laws: Hope, Hype, and Unintended Consequences." Annals of internal 

medicine 163.10 (2015): 796-797. 
303 

Congressional Hearing Testimony I Exploring a Right to Try for Terminally Ill Patients l September 22,20161 The isaac Foundation 

In an attempt to raise the status of Right to Try laws and create confusion around alternative 

approaches to accessing pre-approved drugs, the Goldwater Institute falsely claims that paperwork to 

apply for Expanded Access through the FDA takes almost 100 hours. These claims continue to appear 

in Goldwater publications, testimonies, and in the media, yet are categorically untrue. Debunking 

this myth has been difficult, mostly because this incorrect statistic has been repeated ad nauseam by 

Right to Try proponents. The fact of the matter is that the 100 hours required to complete paperwork 

for the FDA includes work done by the company long before the initiation of a Clinical Trial for any 

given drug.' In truth, the time to complete an application to the FDA for Expanded Access is quick, a 

decision rendered in emergency cases is often made in a matter of hours. 8 To make things even 

smoother, the FDA has recently amended its application and states that it should take no longer than 

45 minutes to complete. As well, they have committed to providing a "concierge service" to help 

physicians complete the form quickly and accurately.' 

So is the FDA truly the barrier they have been made out to be by Right to Try advocates? The data 

says No. FDA documents provide data on Expanded Access applications and approvals from 2009-

2015. In successive years beginning in 2009, the FDA granted approval to 98.4%, 99.9%, 99.7%, 

99.6%, 99.7%, and 99.5% of applications received. 10 While, as Right to Try proponents rightly point 

out, these approximately 1200 applications received per year do not account for those that were never 

submitted to the FDA in the first place, what is clear is that the FDA grants access to the vast majoriry 

of patients who request it. Rather than demonizing the FDA, a more fruitful approach would be to 

investigate why some patient requests for access to investigational drugs are never submitted to the 

FDA. 

Where then does the discrepancy lie between the many Americans needing access to life-saving drugs 

and the few approvals being granted? Many would say the fault lies with the pharmaceutical 

companies directly." Companies ofi:en feel that allowing access outside of the clinical setting could 

negatively impact the approval process for drugs under development. The fear that negative adverse 

events that take place could lead to a slowing or complete halt of a clinical trial is real and widespread 

throughout the industry. 

7 "How a Physician Can Work With a Not Yet Approved Drug Through ... " 2016. 15 Sep. 2016 

<http://thehealthcareblog.com/blog/20 16104117 /far-from-evidence-based-prescribing-the-world-of-compassionateuse/> 

8 "How a Physician Can Work With a Not Yet Approved Drug Through .. ." 2016. 17 Sep. 2016 

<http:/ lthehealthgareblog .com/blog/20 1610411 7 /far-from-evidence-based-prescribing-the-world-of-compassionateuse/> 

9 Martin, Caitlyn. "Questioning the Right in State Right to Try Laws: Assessing the Legality and Effectiveness of 

These Laws." Ohio St. LJ 77 (2016): 159. 

10 "Expanded Access (Compassionate Use)> Expanded Access ... - FDA." 2015. 16 Sep. 2016 

<http://www.f<j1J....govfNewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm443572.htm> 

11 Rubin, Rita. "Experts critical of America's right-to-try drug laws." The Lancet386.10001 (2015): 1325-1326. 
304 

Congressional Hearing Testimony l Exploring a Right ro Try for Terminally Ill Patients ! September 22, 2016! The Isaac Foundation 

The FDA, for its part, publicly states that negative adverse events in patients receiving investigational 

drugs via Expanded Access should not or will not impact the approval of medications under 

consideration. In an email directed to my organization in early 2014 while we were trying to gain 

access to an experimental therapy for a young boy su!Tering from a rare and progressive disease, Janet 

Woodcock, Director at the Centre for Drug Evaluation and Research (CDER), stated categorically, 

"As far as I know, and in our collective knowledge here at CDER, adverse events occurring during 

the development program have not delayed the programs. In one case, we know the drug 

development was actually accelerated." Additionally, she stated that "In one case, long ago, an 

investigational product was given to a patient before any human studies were done. The individual, 

unfortunately, died immediately because of the toxicity of the dose given. This was a rare kind of case 

we try to avoid ... " 

In addition, the FDA updated their guidance for industry in June 2016 to address concerns from 

companies about adverse e!Tects and their impact on the approval process. Their guidance states that 

"there are a small number of cases in which FDA has used adverse event information from expanded 

access in the safety assessment of a drug. However, FDA reviewers of these adverse event data 

understand the context in which the expanded access use was permitted (e.g., use in patients with 

serious or immediately life-threatening diseases) ... and will evaluate any adverse event data obtained 

from an expanded access submission within that context. "

12 

As far as I know. and in our 

collective knowledge here at 

CDER. adverse events 

occurring during the 

development program have 

not delayed the programs. In 

one case. we know the drug 

development was actually 

accelerated 

Janet Woodcock, FDA 

Still, in my conversations with many companies that develop, 

test, and market rare disease treatments, the worry persists, and 

any proposed Right to Try legislation does nothing to 

alleviate those concerns. Although pharmaceutical companies 

will not have to report adverse events to the FDA under Right 

to Try, this doesn't remove the fear that an adverse event will 

derail the approval process for drugs. Any adverse event that 

takes place under Right to Try has a good chance of being 

reported in the media, whether local or national. Indeed, for 

companies chat sell stock equity, the U.S Securities and 

Exchanges Commission requires the reporting of incidents 

that may have bearing on the success or failure of 

development of the investigational drug. Such communications frequently find their way from 

shareholders to the general public. Thus, companies' fears of bad news becoming public are as real 

under proposed Right to Try legislation as they are under the Expanded Access program at the FDA. 

12 "Expanded Access to Investigational Drugs for Treatment Use- FDA." 2014. 16 Sep. 2016 

<http://www.fda.gov/downl0ads/drugs/guidancecomplianceregulatorvinformation/guidances/ucm351261. 

pQ!> 
305 

Congressional Hearing Testimony I Exploring a Right to Tl)' for Terminally Ill Patients I September 22,20161 The Isaac Foundation 

Where then, do the solutions lie? First, passing the complete 21st Centuries Cure Act into law would 

go a long way to alleviate concerns about the length of time it takes to have drugs approved in the 

United States. Shortening the length of time it takes to approve drugs can only benefit patients in the 

long run, and it's vital this gets passed into law in short order to help patients in need. Ensuring the 

Andrea Sloan CURE Act is taken up will increase transparency within the pharmaceutical sector and 

ensure companies publicly state their policy on expanded access to unapproved drugs. It will also 

ensure patients denied access are given proper rationale for such a decision. 13 

Additionally, we should be promoting enhancements to the FDA's existing Expanded Access Program 

that is showing promise for its high approval rates, transparent data collection, and focus on patient 

safety. While companies are hesitant to have such information collected, such data collected by the 

FDA during Expanded Access can only serve to inform good evidence-based practice and help expand 

our knowledge in a broader and more representative patient population. To alleviate these concerns, 

it is paramount that the FDA work with the pharmaceutical industry to clearly address how adverse 

events outside of the clinical trial setting will impact their path toward approval. 

Work can also be done on an industry level in the short term to ensure access immediately, and there 

is evidence that companies are taking steps to ensure broader access for patients outside the clinical 

setting. 

Case in point-Janssen Pharmaceuticals, in partnership with the NYU Langone Medical centre, 

recently introduced a "transparent, fair, beneficent, evidence based, and patient-focused" program to 

review compassionate use requests for one of their drugs currently being investigated in a clinical trial 

(Daratumumab). 14 An independent review committee (CompAC) was created to review such requests 

in a fair and equitable manner, free from bias based on income, sex, race, nationality, or celebrity 

status. 15 In addition, the committee would render decisions in an expeditious fashion, no more than 5 

days after an application was received. 

Data for the last half of2015 suggest the program is working, and that patients are receiving access to 

the drug they need in an expeditious manner. Of 160 applications received, 62 resulted in 

compassionate use being approved for Expanded Access, with 43 applicants having a non-favourable 

benefit-risk profile and 28 requests deemed ineligible due to not having exhausted all alternative 

therapies. 16 

13 "H.R.6- 114th Congress (2015-2016): 21st Century ... - Congress.gov." 2015. 16 Sep. 2016 

<https://www.congress.go'!/t>illL1_1i!h_:_<cof1gr.,s§ihq_u_s.,:_l:!l!ll§> 

14 Caplan, Arthur L, and Amrit Ray. "The Ethical Challenges of Compassionate Use." JAMA 315.10 (2016): 979-980. 

15 Caplan, Arthur L, and Amrit Ray. "The Ethical Challenges of Compassionate Use." JAMA 315.10 (2016): 979-980. 

16 Caplan, Arthur L, and Amrit Ray. "The Ethical Challenges of Compassionate Use." JAMA 315.10 (2016): 979-980. 
306 

Congre!>Sional Hearing Testimony I Exploring a Right to Try for Terminally ill Patients ! September 22, 2016! The Isaac Foundation 

Taken in context, the 62 patients approved for use under the CompAC program during 6 months in 

2015 made up roughly 5% of all Expanded Access cases approved through the FDA program last year 

alone. Under Janssen/NYU's CompAC model for Expanded Access, patients most in need are 

gaining access quickly and fairly. 

Additionally, BioMarin Pharmaceutical recently implemented an ambitious Early Access Program for 

patients suffering from a fatal and debilitating, heritable condition, CLN2, which is a form of Batten 

disease. The company has implemented this program under the existing FDA regulations governing 

expanded access and the will provide many patients with prompt access to the drug outside the clinical 

trial setting. 

In this case, consistent with its own compassionate use policy and current FDA regulations, BioMarin 

sought and received the treatment protocol because CLN2 is a fatal condition, there are no other 

available treatments, initiation of early access for patients who were not enrolled in the clinical trial 

will not interfere with the clinical investigation of the drug. Enrollment decisions for this treatment 

protocol are being made independent of BioMatin. 17 

Biornarin's program underscores not only that a pathway to early access already exists for both 

individuals and larger patient populations under current Federal law, but also that every disease, 

investigational therapy, clinical trial design, and individual patient are different so benefit-risk should 

be evaluated on a case by case basis. All patients with such conditions deserve hope, but it should be 

balanced on the ability for a company to obtain enough safety and efficacy data that will allow the 

larger patient populations to benefit &om a drug through FDA approval. 

The current FDA Expanded Access Program does just that, rendering these Right to Try laws 

ineffectual. Moreover, the unintended consequence of clinical trial attrition in instances when a 

patient knows they are receiving placebo, which is the case when therapy is delivered through a 

device, is a very real risk of these right to try laws because of the false hope they provide patients. 

These examples show that it's possible to adapt the current system we have in place through the FDA 

to help patients and families gain access to pharmaceutical products outside the clinical trial setting. 

These examples show that it is possible to bridge the gap between patients, patient organizations, the 

FDA, and the pharmaceutical industry. It's examples like these that will provide our patients with the 

Hope they thought was lost, not Right to Try legislation, and we must continue to promote and 

strengthen these programs throughout the United States if we want to see a pivotal shift toward 

broader access to pharmaceutical products for our patients. 

17 "BioMarin Announces Positive Data From Cerliponase Alfa Program for ... " 2016. 16 Sep. 2016 

<http://investors.bmrn.com/releasedetail.cfm?releaseid=958565> 
307 

.,.,..-.... 

:· ~DEPARTMENT OF HEALTH AND HUMAN SERVICES 

-,,;~~~ 

STATEMENT 

OF 

PETER LURIE, MD, MPH 

Food and Drug Administration 

Silver Spring, MD 20993 

ASSOCIATE COMMISSIONER FOR PUBLIC HEALTH STRATEGY AND ANALYSIS 

OFFICE OF POLICY, PLANNING, LEGISLATION, AND ANALYSIS 

U.S. FOOD AND DRUG ADMINISTRATION 

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

BEFORE THE 

COMMITTEE ON HOMELAND SECURITY AND GOVERNMENT AFFAIRS 

U.S. SENATE 

"Exploring a Right to Try for Terminally Ill Patients" 

SEPTEMBER 22, 20I6 

RELEASE ONLY UPON DELIVERY 
308 

INTRODUCTION 

Mr. Chairman, Ranking Member Carper, and Members of the Committee, I am Dr. Peter Lurie, 

Associate Commissioner for Public Health Strategy and Analysis at the Food and Drug 

Administration (FDA or the Agency), which is part of the Department of Health and Human 

Services (HHS). Thank you for the opportunity to be here today to discuss expanded access to 

investigational products 

As a physician, I have personally witnessed the suffering and the dilemmas facing patients and 

their families when they are confronted with serious or life-threatening conditions and limited 

treatment options. Having exhausted other treatments, they may wish to turn to investigational 

products. Prior to approval, Investigational new drugs undergo clinical trials to assess whether 

they can be used safely and deliver efficacious results for a particular indication in humans. FDA 

recognizes that, in many instances, patients with life-threatening diseases are more willing to 

accept the risk associated with investigational products than other patients, especially if they 

have no other available options. 

That is why, for over two decades, FDA has had in place a system to help patients gain access to 

investigational products, and FDA has authorized more than 99 percent of requests between 

20 I 0-2015. 1 To be clear: the best way to hasten access to safe and effective products for the 

largest number of patients is through the clinical trial process. Enrollment in clinical trials helps 

to ensure adequate protection for patients and leads to the collection of vital data that could 

eventually result in FDA approval of the investigational product. Once approval is secured, all 

patients with the condition may receive it, and much wider availability is almost certain to ensue. 

Nonetheless, FDA recognizes that there are circumstances when patients with serious or lifethreatening conditions and no comparable or satisfactory alternative therapy are not eligible for a 

clinical trial, either because of where they live, their age, or some other disqualifYing factor. 

These patients may consider seeking access to investigational drugs, and FDA's expanded access 

program is intended to serve them. 

To qualifY for the program, the patient's treating physician must determine that the patient has a 

serious or life-threatening condition and no comparable or satisfactory alternative therapy. The 

physician then approaches the pharmaceutical company to ask for its agreement that it will 

provide the drug being sought. The company has the right to approve or disapprove the 

physician's request. If the company agrees to the physician's request, the physician can then 

apply to FDA for permission to proceed. Should they do so, they are highly likely to be allowed 

to proceed. As shown in the chart below, FDA has authorized more than 99 percent (711 0/7176) 

of single patient expanded access Investigational New Drug (IND) requests received in Fiscal 

Years 20 I 0-2015. Emergency requests are usually granted immediately over the phone and non1 FDA has multiple expanded access programs for investigational drugs and devices: single patient !NOs and 

protocols (including emergency applications), intermediate size !NOs and protocols and treatment !NOs and 

protocols for widespread use; and- for devices- emergency use, compassionate use, and treatment use 

(http: I lwww jda.gov/Medica/Device s!DeviceRegulationandGuidance/ HowtoMarketY our Device/In vestigationa/Devic 

eExemplion!DE/ucm05l345.htm). There are far more applications for single patient !NOs and protocols, and they 

are the focus of this testimony. 
309 

emergencies are processed in a median of four days. The treating physician is then responsible 

for obtaining informed consent from the patient and approval from an ethics committee before 

administering the drug. 

Ill 

t: 

0 

Ill 

Ill 

·-E 

.c 

::::J 

V) 

-

0 

llo.. 

C1l 

.c 

E 

::::J 

z 

CBER and COER Single Patient Expanded Access 

INO Submissions, 

2000 

1800 

1600 

1400 

1200 19 " 

1000 1- -

800 r- - -

600 r- - -

400 r- - -

200 '- - -

0 ~ ~ 

-

FY 2010 - 2015 

11 

... v 

- f8_ .L;) - 1-

- - t-- 1-

- - I-- f-

- - I-- f-

- - I-- 1-

- - ~ ~ 

• Not Allowed to 

Proceed 

• Allowed to Proceed 

Data include emergency and non-emergency single patient IND submissions. 

CBER =Center for Biologics Evaluation and Research; CDER =Center for Drug Evaluation and Research 

'For FY 10 and FY II, the reporting period was October 13 througb October 12 of the following year. 

Source: httv:I!Www.fda.govldownloads/NewsEvents,PublicHealthFocus/Exoanded.AccessComvassionaleUseiUCM47 I 305.odf 

Access to investigational products requires the active cooperation of the treating physician, 

industry and FDA in order to be successful. In particular, the company developing the 

investigational product must be willing to provide it- FDA cannot force a company to 

manufacture a product or to make a product available. Companies might have their own reasons 

to tum down requests for their investigational products, including their desire to maintain their 

clinical development program or simply because they have not produced enough of the product. 

Based on information available, it appears that pharmaceutical companies tum down 

considerably more applications from physicians than does the Agency. For example, one 

2 
310 

company indicated that it had turned down 98 of 160 applications for a single drug in a sixmonth period. 2 Another company reportedly turned down "hundreds" of applications for its drug 

over two years.3 In contrast, over six years, FDA has put on clinical hold 66 applications from 

the thousands it has received. 

With regard to investigational medical devices, FDA also has a process in place for responding 

to requests for expanded access to these products as. Since 2012, we have approved more than 

98 percent of these requests. In 2015, FDA approved 99 percent4 of expanded access requests 

received under an Investigational Device Exemption. Unlike drugs and biologics, emergency use 

of investigational devices does not require prior authorization from FDA, as long as certain 

criteria are met, such as submitting a report of the emergency use within five working days from 

the time the sponsor learns ofthe use. 

Since the expanded access program began, FDA has worked to improve it. FDA established an 

expedited telephone process for daytime and after-hours emergency requests for expanded 

access, and revamped the regulations regarding expanded access to investigational drugs to make 

the process and responsibilities of physicians more clear and concise. More recently, in response 

to feedback from physicians that completing the two expanded access forms was timeconsuming, in June 2016, FDA released a single new form (FDA form 3926) for individual 

patient expanded access. This form is estimated to take 45 minutes to complete and requires just 

one attachment (the previous one required up to eight). Along with the new form, we released 

step-by-step instructions on how to complete it. We also released a Questions and Answers 

guidance that explains what expanded access is, when and how to request expanded access, and 

the type of information that should be included in requests. At the same time, we released a third 

guidance that explains the regulations regarding when and how patients may be charged for 

investigational drugs, notably that the sponsor may recover only its direct costs associated with 

making the drug available to the patient. Simultaneously, FDA revamped its expanded access 

website and produced Fact Sheets for physicians and patients. Almost immediately, physicians 

began to take advantage of the new form. In addition to web pages directed specifically toward 

patients, physicians and industry, FDA has staff available to assist physicians and patients in 

understanding how to apply for expanded access. 

However, even patients with serious or life-threatening diseases and conditions require 

protection from unnecessary risks, particularly as, in general, the products they are seeking 

through expanded access are unapproved- and may never be approved. Moreover, FDA is 

concerned about the ability of unscrupulous individuals to exploit such desperate patients. Thus, 

with every request, FDA must determine that the potential patient benefit from the 

2 Caplan AL, Ray A. The ethical challenges of compassionate use. Journal of the American Medical Association 

2016;315:979-80. 

3 Usdin S. How Chimerix. FDA grappled with providing compassionate access to Josh Hardy. BioCentury on 

BioBusiness, March 31, 2014. Available at: http:llwww.biocentury.com/biotech-pharma-news!regulation/2014-03-

31/how-chimerix-fda-grappled-with-providing-compassionate-access-tojosh-hardy-a7 (accessed September II, 

2016). 

4 99.04% of208 evaluable submissions received. More information is available on this website: 

http:!!www.fda.gov/Medica/Devices/DeviceRegulationandGuidance/HowtoMarketYourDevice!Jnvestigationa/Devic 

eExemption!DE!ucm051345.htm. 

3 
311 

investigational drug justifies the potential risks and that the potential risks are not unreasonable 

in the context of the disease or condition to be treated. For this reason, even as it permits more 

than 99 percent of applications to proceed, FDA makes meaningful changes in 11 percent of 

expanded access IND applications to help ensure patient safety, including changes in dosing, 

safety monitoring, and informed consent. 

While we welcome suggestions that might improve the expanded access process, we would 

caution against any changes that would reduce FDA's role in expanded access or that might 

undermine the crucial clinical trial development process. As noted, enrollment in clinical trials 

remains the best option for patients wishing to gain access to investigational medical products as 

it assures adequate protection for patients and leads to the collection of data that could eventually 

result in FDA approval of the investigational therapy and thus widespread availability. Criticism 

that effective therapies are being kept from Americans is unfounded; FDA is committed to new 

drug development. In 2014, consistent with a trend that has been in place for many years, 60 

percent of new molecular entities were approved in the United States before any other country. 5 

In calendar year 2015, FDA approved 45 new molecular entity drugs. About 47 percent of these 

drugs were approved to treat rare or "orphan" diseases that affect 200,000 or fewer Americans. 

It is therefore critical that we maintain and not undermine the clinical trials process that has 

served Americans so well. Most fundamentally, the Agency is concerned that some legislative 

proposals could undermine FDA's ability to protect and promote the public health through 

science-based regulation of drugs and devices. FDA's expanded access process strikes a careful 

balance between helping to facilitate patient access to investigational therapies, while providing 

patients with appropriate human subject protections and preventing interference with the 

product's development program. Upsetting this balance has the potential to expose patients to 

unreasonable risks and stymie the development of medical products that could benefit us all. 

Notably, FDA often has safety information unavailable to the public that is an important 

consideration in these decisions. 

Finally, prohibiting the Agency from reviewing adverse events that occur in expanded access use 

would be detrimental and raise significant ethical issues. Given that the Agency is charged with 

assessing the safety and effectiveness of medical products, the Agency cannot ignore valid 

scientific information. Of course, the Agency understands that adverse events that arise during 

expanded access use must be interpreted with caution. However, over the last decade, spanning 

almost I I ,000 expanded access requests, there were only two instances in which a clinical hold 

was placed on commercial drug development due to adverse events occurring under expanded 

access INDs or protocols. In both instances, the development of the drugs continued after issues 

were addressed and the holds were lifted. FDA also recently published a guidance entitled 

Expanded Access to Investigational Drugs for Treatment Use -Questions and Answers. This 

guidance makes clear that the Agency understands that expanded access is a very particular 

context (sicker patients, multiple illnesses, concurrent medications, etc.) and that FDA takes that 

context into account when interpreting adverse events. 

5 Scrip Magazine (1982 ·2006), Phannaprojects/Citcline Pharma R&D Annual Review (2007 ·2014). 

4 
312 

CONCLUSION 

Clinical trials remain the best option for patients wishing to gain access to investigational 

products and bringing new, innovative products to market through the approval process remains 

the best way to assure the development of and access to safe and effective new medical products 

for all patients. 

For those patients who cannot participate in trials, and are left in the difficult, heart-wrenching 

position of having no other therapeutic options, FDA is proud of its expanded access process for 

individual patients. It has stood the test of time and serves over 1,000 patients each year. FDA 

continues to work to improve the program and expects the new short form and the associated 

streamlined process to continue to help patients who cannot participate in clinical trials. 

I am happy to answer any questions you may have. 

5 
State-level Right To Try legislation 

31 States with Right to Try 

States that vetoed Right To 
314 

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Food and Drug Administration 

Individual Patient Expanded Access 

Investigational New Drug Application (IND) 

(Title 21, Code of Federal Regulations (CFR) Part 312) 

1. Patient's Initials 

J.a. Initial Submission 

0 Selectthis box if this form 1s an 

mitial submission for an individual 

patient expanded access !ND, 

and complete only fields 4 

through 8, and fields 10 and 11. 

4. Clinical Information 

Indication 

, 3.b. Follow-Up Submission 

I 

0 Select this box if this form accompanies 

a follow-up submission to an existing 

individual patient expanded access !NO, 

and complete the items to the right in this 

section, and fields 8 through 11. 

Form Approved: OMB No. 0910-0814 

Expiration Date: April30, 2019 

See PRA Statement on last pagR 

2. Date of Submission (mm/ddlyyyy) 

I investigational Drug Name 

I 

I Physician's IND Number 

I 

Brief Clinical History (Patient's age, gender, weight, aflergies, diagnosis, pdor therapy, response to prior therapy, reason for 

request, including an explanation of why the patient lacks other therapeutic options) 

5. Treatment Information 

Investigational Drug Name 

Name of the entity that will supply the drug (generafly the manufacturer) 

FDA Review Division (if known) 

Treatment Plan (Including the dose, route and schedule of administration, planned duration, and moniton'ng procedures. Also include 

modifications to the treatment plan in the event of toxicity.) 

6. Letter of Authorization {LOA), if applicable (generally obtained from the manufacturer of the drug) 

0 I have attached the LOA. (Attach the LOA; if electronic, use normal PDF functions for file attachments.) 

Note: If there is no LOA, consult the Form Instructions. 

7. Physician's Qualification Statement (Including medical school attended, year of graduation, medical specialty, state medical 

license number, current employment, and job title. Altemativefy, attach the first few pages of physician's curriculum vitae (CV), 

provided they contain this infom1ation. If attaching the CV electronically, use normal PDF functions for file attachments.) 

FORM FDA 3926 (2/16) Page 1 of2 
315 

9. Contents of Submission 

This submission contains the following maten'als, which are attached to this fonn (select all that apply). If none of the following apply to the 

follow-up communications, use Fonn FDA 1571 for your submission. 

0 Initial Written !NO Safety Report 0 Change in Treatment Plan 

0 Follow-up to a Written !NO Safety Report 

0 Annual Report 

0 General Correspondence 

0 Response to FDA Request for Information 

0 Summary of Expanded Access Use {treatment completed) 0 Response to Cllnlcal Hold 

10. Request for Authorization to Use Form FDA 3926 

0 I request authorization to submit this Form FDA 3926 to comply with FDA's requirements for an individual patient expanded access IND. 

11. Certification Statement: I will not begin treatment until 30 days after FDA's receipt of a completed application and all 

required materials unless I receive earlier notification from FDA that treatment may begin. I also agree not to begin or 

continue clinical investigations covered by the IND if those studies are placed on clinical hold. I also certify that I will obtain 

informed consent, consistent with Federal requirements, and that an Institutional Review Board {IRB) that complies with the 

FederaiiRB requirements will be responsible for initial and continuing review and approval of this treatment use. I understand 

that in the case of an emergency request, treatment may begin without prior IRB approval, provided the IRB is notified of the 

emergency treatment within 5 working days of treatment. I agree to conduct the investigation in accordance with all other 

applicable regulatory requirements. 

WARNING: A willfully false statement is a criminal offense (U.S.C. Title 18, Sec. 1001). 

Signature of Physician Date 

required f1e!ds. For a hst of requ1red f1elds 

IND Number DYes D.No 

This section applies only to requirements of the Paperwork Reduction Act of 1995. 

'DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.' 

The burden time for this collection of information is estimated to average 45 minutes per response, including the 

time to review instructions, search existing data sources, gather and maintain the data needed and complete 

and review the collection of information. Send comments regarding this burden estimate or any other aspect 

of this information collection, including suggestions for reducing this burden, to: 

Department of Health and Human Services 

Food and Drug Administration 

Office of Operations 

Paperwork Reduction Act (PRA) Staff 

PRAStaff@fda.hhs.gov 

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of 

information unless it displays a currently valid OMB number." 

FORM FDA 3926 (2/16) Page 2 of 2 
316 

Patient Access to Investigational Therapies 

Many states across the country are considering so-called "Right to Try" legislation to provide patients with access 

to investigational therapies before they are approved by FDA, However, for over two decades, FDA has had 

processes in place to do just that. Expanded access, which is sometimes called "compassionate use," supplements 

the clinical trials process. FDA believes enrollment in clinical trials remains the best option for patients wishing to 

gain access to investigational drugs-it assures adequate protection for patients and leads to the collection of data 

that could eventually result in FDA approval of the investigational therapy, which provides the broadest avallabi!ity 

to patients. Patients who are not eligible for a clinical trial because of where they live, their age, or some other 

disqualifying factor have the option to seek expanded access if they have serious or life-threatening conditions and 

no comparable or satisfactory alternative is available. 

FDA acts quickly in response to expanded access requests and a !lows almost all of them to proceed. ln fact, FDA 

authorized more than 99 percent of individual patient expanded access requests received in Fiscal Years 2010-14. 

Emergency requests are often granted immediately over the phone. For non-emergencies, the Agency strives to 

respond promptly and, in general, does not take longer than 30 days. Moreover, FDA continues to improve its 

processes. !n response to feedback from physlcians that the expanded access form was challenging, in February 

2015, FDA announced the development of a new draft form for individual patient expanded access that is 

estimated to take only about 45 minutes to complete. 

Expanded access to investigational treatments requires the active involvement and cooperation of parties other 

than FDA, including drug companies and healthcare providers. FDA can encourage drug companies to offer 

expanded access to their investigational therapies, but companies may choose not to do so for various reasons, 

including lack of available drug or a desire to focus their attention on completing the clinical trials necessary to 

support FDA approval. 

Facts: 

FDA has a longstanding and we!t~estab!!shed process for individual patients to obtain access to 

investigational therapies-expanded access, which is sometimes called compassionate use. 

FDA allows almost aU expanded access requests to proceed: more than 99 percent of individual patient 

expanded access requests made from 2010-14 were granted. 

FDA responds to individual patient expanded access requests quickly; emergency requests are often 

granted immediatelY over the phone. For non-emergencies, the Agency strives to respond promptly and, 

in general, does not take !anger than 30 days. 

FDA is improving expanded access to make it easier to apply; a new form for individual patient expanded 

access requests is estimated to take physicians only about 4S minutes to complete. 

FDA is an important part of the process and helps to ensure patients are adequately protected from unnecessary 

risk. The independent scientific review provided by FDA is an essential component of patient protection, 

particularly because one is considering treatments for which safety and efficacy have not been demonstrated. 

Contact Us 

For more information, please contact FDA's Office of Legislation at 301-796-8900, or see FDA's website: 

bJ!fJ.J/..}AJWW .flli,q_yj__f.J:;.QQ.OJJ.tQ_[\_f~C_i?. 

Updated: June 2016 
317 

Post-Hearing Questions for the Record 

Submitted to the Honorable Ian Calderon 

From Senator Jon Tester 

Homeland Security and Government Affairs Committee Hearing: 

"Exploring a Right to Try for Terminally Ill Patients" 

September 22,2016 

1. How are patients protected from fraudulent practices under right to try laws that shield 

manufacturers, dispensers, and prescribers from liability regarding experimental 

treatments? 

Response: Any treatment that is accessed under a state Right to Try law must be undergoing a current clinical trial or evaluation by the FDA. We heard concerns in California 

that people would be preyed upon but this is simply not possible. No one is going to 

spend hundreds of millions of dollars to get a drug to a stage 2 or 3 clinical trial in order 

to prey upon terminally ill people. The only drugs and devices available under right to try 

are those that are being actively and safely used in FDA-approved clinical trials. 

Furthermore, federal law prevents any drug company from making a profit on a drug that 

is not yet commercially available. So patients are protected on the financial front as well. 

2. In the absence of a federal right to try law, what steps do you recommend that the Food 

and Drug Administration take to improve patients' ability to request access to 

experimental treatments? 

Response: The FDA could adopt Right To Try as its policy without a federal law. The 

agency could model its compassionate use process on Australia's, which allows doctors 

to administer investigational medications to their patients without federal permission in 

advance, but requires the doctor to inform the Australian equivalent to the FDA that a 

patient is being treated outside a clinical trial process. The change here is subtle; it's 

eliminating the "must ask permission first" step and transforming it into an "informationsharing to advance science" process. 

Terminal patients should have access to drugs that have been approved in other 

developed countries. Right now only the very wealthy can afford to travel to other 

countries to have access to treatments that are widely available, safe, and saving lives. 

We should not put middle-class and working-class Americans at a disadvantage because 

they don't have the financial resources to travel abroad. 
318 

Post-Hearing Questions for the Record 

Submitted to the Honorable Jim Neely 

From Senator Jon Tester 

Homeland Seeurity and Government Affairs Committee Hearing: 

"Exploring a Right to Try for Terminally Ill Patients" 

September 22, 2016 

I. How are patients protected from fraudulent practices under right to try laws that shield 

manufacturers, dispensers, and prescribers from liability regarding experimental 

treatments? 

Patients' responsibility. 

2. In the absence of a federal right to try law, what steps do you recommend that the Food 

and Drug Administration take to improve patients' ability to request access to 

experimental treatments? 

Expand access. 
319 

Post-Hearing Questions for the Record 

Submitted to Richard Garr 

From Senator Jon Tester 

Homeland Security and Government Affairs Committee Hearing: 

"Exploring a Right to Try for Terminally Ill Patients" 

September 22, 2016 

1. How are patients protected from fraudulent practices under right to try laws that shield 

manufacturers, dispensers, and prescribers from liability regarding experimental 

treatments? 

There are several layers of "protection" built into the bill. First, any drug which can be 

prescribed under the bill has to have passed at least one FDA safety trial AND still be under 

FDA review. This insures that no "snake oil" is being sold. It is extremely expensive to conduct 

trials (remember this only applies to fatal diseases) like this and only serious scientific efforts 

make it that far; Second, it has to be requested by a licensed MD; another filter to screen out high 

pressure sales tactics by charlatans; finally, all of the safety and other information on any drug in 

an FDA trial is available on line, and both the patients and the doctors have easy, ready access to 

the information needed to calculate the risks involved with any experimental drug. 

2. In the absence of a federal right to try Jaw, what steps do you recommend that the Food 

and Drug Administration take to improve patients' ability to request access to 

experimental treatments? 

It's hard to envision any drug owner (company) being enthused about easier access to their 

experimental drugs Without the Federal level protection. The 21st Century Cures act (if it passes 

this week in the senate) gives the FDA some additional flexibility to "grease the skids" so to 

speak, but none of the provisions address the potential liability issues that this act does. So from 

a practical point of view, I think it would be very hard to envision any steps that would be 

effective without passage of this bill. 
320 

Post-Hearing Questions for the Record 

Submitted to Dr. Peter Lurie 

From Senator Ron Johnson 

"Exploring a Right to Try for Terminally Ill Patients" 

September 22,2016 

1. Does the FDA Commissioner believe terminal patients should be permitted to access 

Phase 1 approved treatments that are continuing toward final drug approval if: no other 

treatment options are available and enrollment in a clinical trial is not possible; the 

patient, his or her doctor, and the manufacturer consent; and if authorized by state law? 

2. Why was the FDA's streamlined application for expanded access, announced in February 

2015, not finalized until June 2, 20 16? 

3. Will the FDA promulgate regulations or guidance advising pharmaceutical companies as 

to how, if at all, the FDA will use adverse events that occur outside of clinical trials 

conducted in accordance with FDA approved protocols (through FDA's expanded access 

program, or otherwise) in the FDA's decision-making process about whether a trial can 

continue and! or the drug can be approved? 

4. How often does the FDA update the information made available to patients on 

clinicaltria1s.gov? Will the Commissioner commit to ensuring this information is up-todate and accurate so that patients can learn about and pursue their options under clinical 

trials, expanded access, and right to try? What specific steps will the FDA take, and in 

what timeframe, to ensure this commitment? 

5. Will the FDA provide the Committee with a list of each treatment and the number of 

patients treated for all compassionate use approvals over the past year? 

6. If the FDA becomes aware that a physician or manufacturer is administering or making 

available to patients a treatment that has not received approval of a New Drug 

Application and remains in clinical study phase, pursuant to a state-passed right to try 

law, will the FDA attempt to enforce Federal laws against the physician or manufacturer? 

Has the FDA ever referred a physician or manufacturer to the Department of Justice, 

another law enforcement agency, or a state medical board for making treatments still in 

clinical trials available to patients under a state-passed right to try law? How does the 

FDA use information about a physician or manufacturer providing treatments pursuant to 

a state right to try law in its approval process for new drugs? 
321 

7. What policy changes would the FDA support to speed access to treatments for those with 

life-threatening illnesses (not including the FDA's expanded access program)? Does the 

FDA support reciprocal drug or device approval with international peer agencies? Does 

the FDA support personal importation of drugs or devices fully approved in other 

countries? 

8. How are questions for advisory committee consideration developed? How does the FDA 

or a committee ensure they are presented with appropriate questions that do not 

unnecessarily hinder evaluation of a drug's effects? What is the public's role in 

developing the questions? 

9. Who ensures the FDA is following the requirements of the Food and Drug 

Administration Safety and Innovation Act? 

10. The FDA has finally made public a decision on the Priority Review of a NDA for a 

treatment ofDuchenne muscular dystrophy. On February 8, 2016, the FDA delayed the 

Prescription Drug User Fee Act (PDUFA) date by three months to May 26, 2016? Why 

did the FDA miss this goal date by nearly four months? Has the FDA approved any 

expanded access applications for this treatment? 

11. What influence or say does the FDA have over the exclusionary criteria employed in IND 

clinical study protocols? 

From FDA, February 2017: 

The QFRs were with the Department when the Administration switched Ul!{ortunately that 

means they were closed However, Senator Johnson's QFRs were identical to the questions he 

posed to Secretary Burwell in a letter. Attached is the response that 1 understand HHS sent to the 

Senator on January 18, 2017. 
322 

!H P·\R I \11·'-! ()! Ill·\! ! H ,\. Hl \L\\ \I R\ ICh <H·f!CLO! fllt· ~H RJ·IARY 

The Honorable Ron Johnson 

Chaim1an 

Committee on Homeland Security and Governmental Affairs 

United States Senate 

Washington, DC 20510 

Dear Mr. Chairman: 

JAN 1 B 2017 

Thank you for your letter of October 21, 2016, concerning actions by the Food and Drug 

Administration (FDA) regarding potential enforcement or disciplinary actions directed at parties 

acting pursuant to state "right to try" laws. Enclosed are responses to the questions you posed in 

your letter. 

1 hope this infonnation is helpful to you. Thank you for your continued interest in the important 

work of FDA. 

cc: The Honorable Claire McCaskill 

Ranking Member 

Enclosure 

Sincerely, 

Q· a. S:o j,/0. 

u~ R. Esque: (j'~ 1 

Assistant Secretary for Legislation 
323 

Enclosure 

1. Does the Department of Health & Human Services believe terminal patients should be 

permitted to access treatments that have completed Phase I testing and arc continuing 

toward final drug approval if no other treatment options are available and enrollment 

in a clinical trial is not possible; the patient, his or her doctor, and the manufacturer 

consent and if authorized by state law? 

The Food and Drug Administration (FDA or the Agency) agrees that patients who cannot enroll 

in a clinical trial and who are in such a difficult situation should have a path to receiving 

medications that might help them, and that is precisely what the expanded access program seeks 

to do. It is important to acknowledge there is limited information available regarding the safety 

profile and effectiveness of an investigational drug during and at the conclusion of phase I 

studies. The purpose of phase I studies is to gain preliminary information about the safety 

profile of an investigational drug at various doses and phase I studies generally do not assess 

effectiveness. The population studied (healthy volunteers versus patients with the 

disease/condition) and the duration of exposure (single versus repeated dosing) depends on the 

nonclinical safety profile of the investigational drug and the disease/condition for which the 

investigational drug is being studied. More often than not, much more is learned about the safety 

profile of a drug after phase I studies, as greater numbers and more varied patient populations 

participate in studies of the investigational drug over a longer period of time during development 

of the drug and even after approval. 

It is important that FDA is involved in expanded access efforts for both patient safety and the 

drug development approval process. This includes considerations such as safety signals that may 

have arisen during prior use of the drug, if the risks of the drug are likely to be outweighed by its 

benefits, if the person offering the drug has a history of fraudulent behavior, and if enrollment in 

clinical trials is threatened. 

2. Why was the FDA's streamlined application for expanded access, announced in 

February 2015, not finalized until June 2, 2016? 

In June 2016, FDA issued Form FDA 3926 and three final guidances. FDA adheres to good 

guidance practices. 1 This process includes FDA providing a draft guidance allowing for public 

comment and then FDA carefully reviewing and considering comments as the Agency works to 

fmalize the guidance document. Clearing Form FDA 3926 involved a separate process, which 

included review and clearance by the Office of Management and Budget (OMB) under the 

Paperwork Reduction Act of 1995 (PRA). The final OMB approved form took into account 

comments received during the PRA notice and comment process and the guidance development 

process, as well as OMB review, and included modification of the form to include certain 

follow-up submissions. 

1 21CFRIO.II5 
324 

3. Will HHS or the FDA promulgate regulations or guidance advising pharmaceutical 

companies as to how, if at all, the FDA will use adverse events that occur outside of 

clinical trials conducted in accordance with FDA approved protocols (through FDA's 

expanded access program, or otherwise) in the FDA's decision-making process about 

whether a trial can continue and/or the drug can be approved? 

As is the case for all Investigational New Drug Application (INDs), physicians submitting 

individual patient expanded access requests are required to report adverse reactions to the FDA2 

The Agency must be made aware of adverse events, which raise legitimate scientific and public 

health concerns. Agency awareness of adverse events is critical for efforts to ensure that the 

approved labeling contains the essential scientific information needed for the safe and effective 

use of the drug. Reporting allows the FDA the opportunity to evaluate the events (in the proper 

context) and, if we tlnd it appropriate to do so, require that prescribers be informed, via the 

drug's labeling, of these potential adverse events and/or of steps to take to try to prevent them. 

As noted above, FDA interprets expanded access adverse events in their appropriate context. 

Agency officials consider the disease state of the patient, which may be further advanced than 

those of clinical trial participants. Patients receiving access to investigational products through 

expanded access are also often receiving other therapies for their disease or condition, and may 

be receiving therapies for comorbidities that disallow them from entering the clinical trial for the 

investigational product. There are a small number of cases for which FDA has included adverse 

event information from the expanded access program in the safety assessment of a drug, 

although in many cases, the information is considered anecdotal, outside the context of the trial 

data. This is explained in Question 25 of our Questions and Answers Guidance, one of the three 

released in June 3 However, it is important to note that FDA is aware of at least two marketing 

2 See 21 CFR 312.32 

1 Q25: What data and information must sponsors submit as follow-up for approved expanded access I NOs or 

protocols? 

A25: As with any IND, in all cases of expanded access, sponsors are responsible for submitting IND safety reports 

and annual reports (when the IND or protocol continues for I year or longer) to FDA as required under 21 CFR 

312.32 and 312.33 (see§ 312.305(c)). 

For individual patient expanded access, the regulations in § 312.3 J O(c)(2) specify that, at the conclusion of 

treatment, the sponsor must provide to FDA a written summary of the results of the expanded access use, including 

adverse effects. 

From a public health perspective, early identification of important adverse events is beneficial. For example, a 

relatively rare adverse event might be detected during expanded access use, or such use might contribute safety 

information for a population not exposed to the drug in clinical trials. There are a small number of cases in which 

FDA has used adverse event information tram expanded access in the safety assessment of a drug. However, FDA 

reviewers of these adverse event data understand the context in which the expanded access use was permitted (e.g., 

use in patients with serious or immediately life-threatening diseases or administered in a clinical setting (not clinical 

trial) and will evaluate any adverse event data obtained from an expanded access submission within that context. 

Expanded access INDs and protocols are generally not designed to determine the efficacy of a drug; however, the 

expanded access regulations do not prohibit the collection of such data. Because expanded access JNDs or protocols 

typically involve uncontrolled exposures (with limited data collection), it is unlikely that an expanded access IND or 

protocol would yield efficacy information that would be useful to FDA in considering a drug's effectiveness. 

2 
325 

applications for which clinical safety data from the expanded access program was used to 

establish a safety database large enough to adequately assess the risks versus benetits of the 

treatments: BLA 125327 for Voraxa¥e (glucaridase) and BLA 125359 for Erwinaze 

(aspariginase Erwinia chrysanthemi). The additional safety data generated from the expanded 

access program provided infonnation needed to support the safety of these drugs for which 

patient exposure in the efficacy trials was limited. 

We understand that sponsors are concerned that adverse events occurring in expanded access 

might endanger a clinical development program. To understand that issue better, FDA has 

reviewed the number of clinical holds placed on clinical development programs due to adverse 

events reported in the context of expanded access. Over a ten year period, of 1,033 unique 

Expanded Access INDs, only two were placed on clinical hold (0.2%). In both cases, the 

development of the drugs continued after the holds were lifted. 

4. How often does the FDA update the information made available to patients on 

clinicaltrials.gov? Will you commit to ensuring this information is up-to-date and 

accurate so that patients can learn about and pursue their options under clinical trials, 

expanded access, and right to try? What specific steps will HHS take, and in what 

timeframe, to ensure this commitment? 

As you may be aware, ClinicalTrials.gov is a data bank maintained by the National Institutes of 

Health (NIH). On September 21,2016, HHS issued a final rule on the submission of registration 

and results information for certain clinical trials involving FDA-regulated drug, biological, and 

device products. The final rule, which is effective January 18,2017, with a compliance date of 

April 18, 2017, clariftes and furthers the implementation of Title Vlll of the Food and Drug 

Administration Amendments Act of 2007. Under the final rule and the statute, responsible 

parties have regulatory and statutory obligations to update the infonnation submitted to 

Clinica!T rials.gov. The tina! rule inc] udes a description of various potential legal consequences 

for not complying with the requirements. These include potential grant funding actions, civil 

monetary penalty actions, and civil and criminal court actions. FDA and NIH have already 

begun to provide information and training sessions (webinars, etc.) so that clinical trial sponsors 

and investigators understand their Clinica!Trials.gov responsibilities under the final rule, 

including those involving expanded access. fDA is making its ClinicaiTrials.gov compliance 

program part of its bioresearch monitoring program, a robust compliance program which 

encompasses critically important responsibilities of those sponsoring and conducting clinical 

trials. 

The final rule fully implements the statutory provision requiring the submission of information to 

Clinica!Trials.gov about the availability of expanded access for drugs being studied in applicable 

4 Public information on expanded access program that supported approval ofVoraxaze can be found in the medical 

review (page 23, Table 5.1) posted on our website at: 

http://www.accessdata. fda.gov/drugsatfda _ docs/nda/20 12/ 1253270rig I sOOOMedR.pd f and the prescribing 

information for Erwinaze, which can be found at: 

http://www.accessdala.fda.gov/drugsatfda_docs/label/20 16!125359s0881bl.pdf (I st paragraph under section 14 

Clinical Studies). 

3 
326 

drug clinical trials and how to obtain information about such access for persons who do not 

qualify to participate in the clinical trial listed in the Clinica!Trials.gov record. Those clinical 

trial sponsors who also manufacture the drug product and are submitting information to 

ClinicaiTrials.gov must indicate in the registration record whether expanded access is available. 

If available, those sponsors must submit specific information to Clinica!Trials.gov that enables 

patients and health care providers to obtain further information about access to the product. 

Information on the availability of expanded access must be updated, according to the timclines 

specified in the final rule, when changes occur. 

5. Will HHS provide the Committee with a list of each treatment and the number of 

patients treated for all expanded access approvals over the past year? 

Consistent with longstanding Agency practice, we do not discuss the substance of matters that 

may be pending before the Agency. This practice helps to ensure the integrity of the review 

process. However, generally speaking, in FY 2015, there were 1,278 individual patient 

expanded access IND submissions, of which 1,268 were allowed to proceed. This includes the 

FDA's Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation 

and Research (CBER). In calendar year 2015, there were 375 submissions requesting approval 

for compassionate use of a device, of which 3 71 were approved. 

6. If the FDA becomes aware that a physician or manufacturer is administering or 

making available to patients a treatment that has not received approval of a New Drug 

Application and remains in clinical study phase, pursuant to a state-passed right to try 

law, will the FDA attempt to enforce Federal laws against the physician or 

manufacturer? Has the FDA ever referred a physician or manufacturer to the 

Department of Justice, another law enforcement agency, or a state medical board for 

making treatments still in clinical trials available to patients under a state-passed right 

to try law? How does the FDA use information about a physician or manufacturer 

providing treatments pursuant to a state right to try law in its approval process for new 

drugs? 

FDA is not aware of any instances in which the Agency has made such referrals. 

FDA would evaluate how to respond on a case-by-case basis. 

7. What policy changes would HHS support to speed access to treatments for those with 

life-threatening illnesses (not including the FDA's expanded access program)? Does 

HHS support reciprocal drug or device approval with international peer agencies'! Does 

HHS support personal importation of drugs or devices fully approved in other 

countries? 

In May 2014, FDA issued final Guidance for Industry on Expedited Programs for Serious 

Condilions- Drugs and Biologics. The purpose of this guidance is to provide a single resource 

for infom1ation on FDA's policies and procedures for these four programs (fast track 

designation, breakthrough therapy designation, accelerated approval, and priority review 

4 
327 

designation) as well as threshold criteria generally applicable to concluding that a drug is a 

candidate for these expedited development and review programs. 

The Agency believes that any efforts to allow sponsors to gain approval of a drug or device in 

the United States must be accompanied by data demonstrating the safety and effectiveness of the 

product to our satisfaction. 

The United States is the only country that reviews the raw clinical trial data provided by the 

companies seeking approval. Other countries base their approval decisions on the analyses and 

summaries of the data provided by the companies. 

There have been a number of instances in which products were approved in other countries but 

not in the United States, and those products later proved to be problematic in various ways. 

Examples include: 

• Lumiracoxib was a non-steroidal anti-inflammatory drug approved in the European 

Union, Canada, and many other countries for relief of various types of pain. The New 

Drug Application (NDA) for lumiracoxib was rejected by FDA because of a signal of 

liver toxicity. Ultimately, the drug was withdrawn from the market in all but a handful of 

countries because of serious liver toxicity. 

• Rimonabant was an anti-obesity drug that was approved in the European Union and many 

other countries, but not given approval in the United States. Rimonabant was later 

withdrawn from the market because of serious psychiatric problems, including suicide. 

• Ova Check was indicated for the early identification of ovarian cancer and was selfcertified in Europe. FDA's concerns with the product included lack of validation that it 

could predict or detect ovarian cancer and that the manufacturer inflated claims of 

accuracy. FDA did not allow marketing of this product and the company eventually left 

the European market. 

Venaxis' APPYI test was CE marked (Europe's approval standard) in 2013. FDA 

subsequently denied Venaxis' U.S. marketing application. 

FDA recognizes there are circumstances under which a United States citizen may wish to seek 

treatment with an unapproved drug/device that is not domestically available. Information 

regarding FDA's treatment of personal importation of such products, including when individuals 

with serious conditions wish to get treatments that are legally available in foreign countries but 

are not approved in the United States, can be found on FDA's website- see, e.g., Regulatory 

Procedures Manual, 9-2 - Coverage of Personal Importations 

(http:/ fwww. fda.govfiCECI/ComplianceManuals/Regulatory ProceduresManual/ucm 179266.htm) 

and Import Basics- Personal Importation 

(http://www. fda.gov/F or I ndustry/I mportProgram/ImportBasics/ucm4 3 266!.htm ). 

FDA also has a Personal Importation Policy (PIP) that describes FDA's approach to individual 

importation of such drugs for personal use (see Personal Importation Policy (PIP) Frequently 

Asked Questions (F AQs), 

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformationlimportsandexpo 

rtscompliance/ucm297909.pdD. 

5 
328 

Under the PIP, several factors are considered in determining whether the Agency intends not to 

object to certain personal imports of drugs: 

The drug is for use for a serious condition for which effective treatment is not available 

in the United States; 

There is no commercialization or promotion of the drug to United States residents; 

The drug is considered not to represent an unreasonable risk; 

The individual importing the drug verifies in writing that it is for his or her own use, and 

provides contact information for the doctor providing treatment or shows the product is 

for the continuation of treatment begun in a foreign country; and 

Generally, not more than a three-month supply of the drug is imported. 

It is important to remember that unapproved medical products from foreign sources do not have 

the same assurance of safety, effectiveness, and quality as medical products subject to FDA 

oversight. In many cases, such medical products have been found to be contaminated, 

counterfeit, contain varying amounts of active ingredients or none at all, or contain different 

ingredients altogether. 

8. How arc questions for advisory committee consideration developed? How does the FDA 

or a committee ensure they are presented with appropriate questions that do not 

unnecessarily hinder evaluation of a drug's effects? What is the public's role in 

developing the questions? 

Questions that are posed to FDA Advisory Committees are generated by FDA subject matter 

experts. They are designed to elicit answers to the very questions FDA needs to answer in order 

to execute its statutory responsibilities. 

As you know, the Food and Drug Administration Safety and Innovation Act (FDASIA) enacted 

in 2012 required FDA to engage with patient communities to solicit their views during the 

medical product development process. Accordingly, FDA provides the opportunity for 

externally led Patient-Focused Drug Development Meetings. In addition, FDA has conducted 18 

disease-specific public meetings to gather a better understanding of patients' attitudes toward 

their condition and available therapies. 

All of this information goes into FDA's assessment of a drug's development program and, 

implicitly, into how issues are presented to advisory committees. In addition, each advisory 

committee meeting has at least an hour devoted to an Open Public Hearing, during which 

patients and other members of the public may present their concerns. 

6 
329 

Æ 

9. The FDA has finally made public a decision on the Priority Review of a NDA for a 

treatment ofDuchcnne muscular dystrophy. On February 8, 2016, the FDA delayed the 

Prescription Drug User Fee Act (PDUFA) date by three months to May 26, 2016? Why 

did the FDA miss this goal date by nearly four months? Has the FDA approved any 

expanded access applications for this treatment? 

Several factors contributed to the time needed to come to a final determination on this 

accelerated approval. For example, the sponsor submitted new data at two points during the 

review process, requiring more time to conduct review. In addition, it was important to have a 

robust scientific discussion and consider differing views on this complex topic, especially since 

the development program for eteplirsen included serious deficiencies in a number of respects that 

led to difficulties in regulatory review. Also, as seen in documents released by the Agency, there 

was an internal appeal regarding the approval, which required additional time for consideration 

and resolution. 

An expanded access application is a type of an IND (or a submission to an existing IND). We do 

not approve INDs; they are either allowed to proceed or not allowed to proceed. In response to 

the question on whether an expanded access lND has been allowed to proceed for this treatment, 

we do not discuss the substance of an expanded access IND that may be pending before the 

Agency, consistent with longstanding Agency practice. This practice helps to ensure the 

integrity of the review process and the application. 

7