U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON : 

For sale by the Superintendent of Documents, U.S. Government Printing Office

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

48–587 PDF 2008

KETEK CLINICAL STUDY FRAUD: WHAT DID 

AVENTIS KNOW? 

HEARING 

BEFORE THE

SUBCOMMITTEE ON OVERSIGHT AND 

INVESTIGATIONS 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED TENTH CONGRESS 

SECOND SESSION 

FEBRUARY 12, 2008 

Serial No. 110–87 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

COMMITTEE ON ENERGY AND COMMERCE 

JOHN D. DINGELL, Michigan, Chairman 

HENRY A. WAXMAN, California 

EDWARD J. MARKEY, Massachusetts 

RICK BOUCHER, Virginia 

EDOLPHUS TOWNS, New York 

FRANK PALLONE, JR., New Jersey 

BART GORDON, Tennessee 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

BART STUPAK, Michigan 

ELIOT L. ENGEL, New York 

ALBERT R. WYNN, Maryland 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

Vice Chairman 

LOIS CAPPS, California 

MICHAEL F. DOYLE, Pennsylvania 

JANE HARMAN, California 

TOM ALLEN, Maine 

JAN SCHAKOWSKY, Illinois 

HILDA L. SOLIS, California 

CHARLES A. GONZALEZ, Texas 

JAY INSLEE, Washington 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

DARLENE HOOLEY, Oregon 

ANTHONY D. WEINER, New York 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

CHARLIE MELANCON, Louisiana 

JOHN BARROW, Georgia 

BARON P. HILL, Indiana 

JOE BARTON, Texas 

Ranking Member 

RALPH M. HALL, Texas 

FRED UPTON, Michigan 

CLIFF STEARNS, Florida 

NATHAN DEAL, Georgia 

ED WHITFIELD, Kentucky 

BARBARA CUBIN, Wyoming 

JOHN SHIMKUS, Illinois 

HEATHER WILSON, New Mexico 

JOHN B. SHADEGG, Arizona 

CHARLES W. ‘‘CHIP’’ PICKERING, 

Mississippi 

VITO FOSSELLA, New York 

STEVE BUYER, Indiana 

GEORGE RADANOVICH, California 

JOSEPH R. PITTS, Pennsylvania 

MARY BONO, California 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE FERGUSON, New Jersey 

MIKE ROGERS, Michigan 

SUE WILKINS MYRICK, North Carolina 

JOHN SULLIVAN, Oklahoma 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

PROFESSIONAL STAFF

DENNIS B. FITZGIBBONS, Chief of Staff 

GREGG A. ROTHSCHILD, Chief Counsel 

SHARON E. DAVIS, Chief Clerk 

DAVID L. CAVICKE, Minority Staff Director 

SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS

BART STUPAK, Michigan, Chairman 

DIANA DeGETTE, Colorado 

CHARLIE MELANCON, Louisiana 

Vice Chairman 

HENRY A. WAXMAN, California 

GENE GREEN, Texas 

MIKE DOYLE, Pennsylvania 

JAN SCHAKOWSKY, Illinois 

JAY INSLEE, Washington 

JOHN D. DINGELL, Michigan (ex officio) 

ED WHITFIELD, Kentucky 

Ranking Member 

GREG WALDEN, Oregon 

MIKE FERGUSON, New Jersey 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

JOE BARTON, Texas (ex officio) 

(II) 

(III) 

C O N T E N T S 

Page 

Hon. Bart Stupak, a Representative in Congress from the State of Michigan, 

opening statement ................................................................................................ 1 

Hon. Greg Walden, a Representative in Congress from the State of Oregon, 

opening statement ................................................................................................ 5 

Hon. John D. Dingell, a Representative in Congress from the State of Michigan, opening statement ....................................................................................... 6 

Prepared statement .......................................................................................... 8 

Hon. John Shimkus, a Representative in Congress from the State of Illinois, 

prepared statement .............................................................................................. 9 

Hon. Michael C. Burgess, a Representative in Congress from the State of 

Texas, opening statement .................................................................................... 10 

Hon. Charles Grassley, a Senator from the State of Illinois, opening statement ...................................................................................................................... 76 

Prepared statement .......................................................................................... 82 

WITNESSES

Ann Marie Cisneros, Former Senior Research Associate, PPD, Inc. ................... 12 

Prepared statement .......................................................................................... 14 

Paul Herbert Chew, President, U.S. Research and Development Division, 

Sonifi-aventis Pharmaceuticals ........................................................................... 38 

Prepared statement .......................................................................................... 40 

Fred Eshelman, Chief Executive Officer, PPD, Inc. ............................................. 53 

Prepared statement .......................................................................................... 55 

Sharon Hill Price, Chief Executive Officer and Chairman of the Board of 

Directors ................................................................................................................ 63 

Prepared statement .......................................................................................... 65 

SUBMITTED MATERIAL

Department of Health and Human Services, subpoena briefing book, dated 

February 11, 2008, submitted by Mr. Dingell ................................................... 118 

Hon. Chuck E. Grassley, letter of February 6, 2008, to Secretary Leavitt 

and Commissioner von Eschenbach .................................................................... 160 

Chart entitled, ‘‘Study 3014 Problem Sites’’ .......................................................... 185 

Chart entitled, ‘‘Dr. Kirkman-Campbell Site, What Aventis Knew:’’ .................. 186 

(1) 

KETEK CLINICAL STUDY FRAUD: WHAT DID 

AVENTIS KNOW? 

TUESDAY, FEBRUARY 12, 2008 

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS, COMMITTEE ON ENERGY AND COMMERCE, Washington, DC. 

The subcommittee met, pursuant to call, at 11:06 a.m., in room 

2123, Rayburn House Office Building, Hon. Bart Stupak [chairman 

of the subcommittee] presiding. 

Present: Representatives Stupak, Dingell, Ex Officio, Walden, 

Burgess, and Barton, Ex Officio. 

Also Present: Representatives Markey and Shimkus. 

Staff Present: John Sopko, Joanne Royce, David W. Nelson, Kyle 

Chapman, Scott P. Schloegel, Alan Slobodin, and Karen E. Christian. 

OPENING STATEMENT OF HON. BART STUPAK, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF MICHIGAN 

Mr. STUPAK. This meeting will come to order. Today, we have a 

hearing titled Ketek Clinical Study Fraud: What Did Aventis 

Know? 

Before I begin, I have a couple of housekeeping items to discuss. 

On January 29, the subcommittee held a business meeting to issue 

subpoenas for several outstanding requests the Committee has 

made of the FDA. The subpoenas were approved unanimously on 

a 12-0 bipartisan vote. 

While we are pleased that the FDA has produced the agents for 

today’s hearing, we are far less than pleased with the response received yesterday to the committee regarding our subpoena for documents requested almost a year ago, in March of 2007. 

Yesterday afternoon, a letter arrived to the committee signed by 

an assistant secretary for legislation at the Department of Health 

and Human Services, and signed by the chief of staff for the FDA, 

stating that they want to, quote, ‘‘reach alternative solutions,’’ end 

of quote, rather than producing the documents we subpoenaed at 

our January 29 business meeting. 

The letter is troubling on several fronts. First, the subpoena was 

served to the Secretary of Health and Human Services, and he did 

not provide the Committee the courtesy of a response under his signature. Second, there appears to be a continued effort to keep secret the documents we requested. This only causes members to further question what could be so damaging in the materials that the 

Administration wants to stonewall our bipartisan subpoena. 

2 

There is precedent for obtaining briefing book documents from 

both Democratic and Republican administrations without having to 

issue a subpoena. The Secretary was made aware of the precedents. With the committee chaired by Republicans Mr. Bliley and 

Mr. Barton, we received briefing books of FDA commissioners in a 

Democratic administration, Dr. Kessler. They were also obtained 

when chaired by a Democrat, Mr. Dingell, receiving briefing books 

of a commissioner in a Republican administration, Mr. Frank 

Young. 

I find the letter received yesterday to be very disconcerting, and 

will be discussing options with Chairman Dingell and Ranking 

Members Barton and Shimkus in the coming days. 

On a separate note, due to a series of votes in the Senate, we 

will need to call our second panel first and have Senator Grassley 

present his testimony as our second panel. Or when the Senator 

gets here, we will move to his testimony. 

Right now, let’s begin this hearing. Each member will be recognized for 5 minutes for an opening statement. 

I will begin. 

Today, we hold the third hearing by the subcommittee on whether the FDA can fulfill its mandate to protect American people from 

unsafe drugs. Once again, we will be exploring this question in the 

context of the controversial antibiotic, Ketek. 

The deeper the members of this subcommittee dig into the Ketek 

approval process, the more disturbed we become about the entire 

drug approval process. Today’s hearing will shine a spotlight on a 

little-understood and rapidly growing world of private drug research and clinical trials. Specifically, we will examine the data integrity lapses and fraud contained in the large Ketek clinical trial, 

Study 3014, which was initially commissioned to assure the safety 

of Ketek. 

The Ketek clinical study illustrates the failure by all stakeholders—FDA, drug companies, third-party monitors, and institutional review boards—to ensure the integrity of clinical trials used 

to support the safety and approval of new drug applications. 

A year ago, this committee heard testimony from Senator 

Charles Grassley about his repeated attempts to secure information from the FDA and the obstacles the FDA erected to impede his 

investigation of the Ketek approval process. Senator Grassley also 

expressed concern that FDA management discourages, even muzzles, scientific dissent. Sadly, this committee’s parallel investigation of Ketek over the past year has confirmed Senator Grassley’s 

dismal assessment of the FDA. 

Senator Grassley returns today to share the findings contained 

in his recently issued report of the Finance Committee’s ongoing investigation into the safety of Ketek, particularly what he has uncovered regarding the criminal investigations conducted by FDA’s 

Office of Criminal Investigations, OCI, into allegations of fraud in 

connection with Ketek Clinical Study 3014. 

We also welcome back Ann Marie Cisneros, formerly a senior 

clinical research associate with PPD, the contract research organization, CRO, hired by Aventis to monitor Study 3014. Ms. Cisneros 

will open the second panel by explaining why she was convinced 

that Aventis, PPD and Copernicus, the institutional review board, 

3 

all charged with protecting the patients in Study 3014, were well 

aware of the faulty and possibly fraudulent data submitted to the 

FDA by Aventis in connection with the approval of Ketek. We are 

particularly grateful to Ms. Cisneros for sharing her experience 

with this committee, despite attempts by her former employer to 

extort her silence. 

Ms. Cisneros was dispatched in February 2002 to inspect the site 

of Dr. Kirkman-Campbell, who enrolled more patients—407, to be 

exact—into Study 3014, more than any other investigator. Prior to 

her visit, Ms. Cisneros was informed by Dr. Reynolds of extremely 

suspicious activity at the site by other PPD personnel and was 

asked to scrutinize Dr. Kirkman-Campbell’s site and try to bring 

back evidence of fraud. 

After only 2 days at the site, Ms. Cisneros found the site so troubling that she was afraid that Dr. Kirkman-Campbell was endangering patient safety. Consequently, on February 21, 2002, Ms. 

Cisneros called Copernicus, the institutional review board working 

for Aventis, to urge them to intervene to protect patients. Copernicus did nothing. 

Dr. Kirkman-Campbell was ultimately convicted of fraud in connection with Study 3014 and sentenced to nearly 5 years in prison. 

The fraud at the site was detected only after a routine audit by 

the FDA, not because Copernicus or Aventis had warned them. 

Well before the FDA audit, however, Aventis, PPD, and Copernicus 

were all aware of scientific misconduct indicative of fraud at the 

site. 

Evidence before this committee suggests that only a company intent upon ignoring the obvious could have failed to detect fraud in 

Study 3014. At Kirkman-Campbell’s site alone obvious indicators of 

fraud included the following: errors in nearly every informed consent form—date modifications, initials different from the signatures, study coordinator entering dates for subjects and the principal investigator; blatantly forged signature on informed consent 

forms; very limited medical records; use of different color ink on 

medical charts— overwrites, cross-outs—inserts of diagnoses in different colored ink; routine failure to give pregnancy tests to women 

of child-bearing age; study investigator and coordinator unaware of 

definitions of serious adverse event or adverse event special interest; no adverse events for the first 300 patients enrolled with drugs 

known to have adverse events; lab results indicative of blood splitting; lack of proper diagnosis for study eligibility; husbands and 

wives enrolling together; large number of patients randomized in 

the Interactive Voice Response System in a short increment of time 

when the office was closed for lunch and not seeing patients; and 

100 percent compliance by patients taking study medication. 

Aventis, PPD, and Copernicus were aware of this misconduct 

well before Aventis submitted Dr. Kirkman-Campbell’s data to the 

FDA to support the approval of Ketek. At a minimum, Aventis 

should have discontinued enrollment at the site and notified the 

FDA. 

We will also hear today from three FDA criminal investigators 

who investigated misconduct and/or fraud in connection with Ketek 

Study 3014. 

4 

The FDA has done its very best to deny this committee access 

to these agents and their investigatory documents. These agents 

testify today under subpoena. Be assured, however, that we do not 

lightly compel the appearance of witnesses before this subcommittee to discuss criminal investigative matters and would not 

have done so were their testimony not of the utmost importance. 

I would like to remind FDA managers that retaliation against 

any agent for their testimony will not be tolerated by this committee. 

Office of Criminal Investigation Special Agent Robert West led 

the criminal investigation which resulted in the August 2003 indictment and October 2003 conviction of Dr. Kirkman-Campbell for 

fraud in connection with Study 3014. Special Agent West will explain how he tried to convince FDA management in 2003 to expand 

the investigation of fraudulent submission of trial data to include 

other sites and, ultimately, Aventis. However, FDA did not open an 

investigation into possible misconduct of Aventis until 2006, over 

4 years after the study ended. 

In early March 2006, Special Agent Robert Ekey was assigned 

the criminal investigation of Aventis. Today, he will confirm that 

his investigation revealed evidence indicating that Aventis was 

aware of serious data integrity problems at the Kirkman-Campbell 

site, but submitted the site data to the FDA, notwithstanding. 

The investigation languished until shortly after this committee’s 

Ketek hearing last year, when the case was reassigned to Special 

Agent Douglas Loveland. Special Agent Loveland conducted an extensive reinvestigation, and became convinced of Aventis’ guilt. On 

June 21, 2007, he presented FDA’s evidence of Aventis to the 

United States attorney for the District of New Jersey and recommended prosecution. The U.S. Attorney ultimately declined to 

prosecute Aventis, not because of lack of evidence against Aventis; 

the declination letter states instead, Put simply, FDA’s lack of reliance on the faulty study and its subsequent decision to approve 

Ketek despite ongoing investigation into Dr. Kirkman-Campbell’s 

conduct make any conviction against Aventis for fraud in connection with the submission of the study highly unlikely. 

Our final panel consists of the following industry officers: Dr. 

Paul Chew, President of U.S. Research and Development, SanofiAventis Pharmaceuticals; Fred Eshelman, CEO of PPD, the contract research organization hired by Aventis to monitor Study 

3014; and Sharon Hill Price, the CEO of Copernicus Group, an institutional review board hired to protect human subjects of Study 

3014. 

Evidence before this committee suggests that each of these firms 

had direct knowledge of serious misconduct and possible fraud in 

Study 3014, yet none of them notified the FDA. We expect them 

to explain why they did not do so. 

Clinical research has changed dramatically within the last 2 decades. No longer anchored in public sector, clinical trial practice like 

PPD and Copernicus Group is currently big business and largely 

self-regulating. Today’s hearing will demonstrate how some actors 

behave in a climate of self-regulation. 

5 

It may be time to seriously rethink the regulatory framework for 

the clinical trial industry and institutional review boards and contract research organizations. 

That concludes my opening statement. 

Mr. STUPAK. I next would like to turn to my colleague, Mr. Walden, for his opening statement, and thank you for being here today. 

OPENING STATEMENT OF HON. GREG WALDEN, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF OREGON 

Mr. WALDEN. Thank you very much, Mr. Chairman, for calling 

this hearing so our committee can continue to shine a light on what 

transpired with Aventis’ large safety trial of its antibiotic Ketek. 

Protecting the integrity of the FDA drug approval process is a 

priority for me and for all members of this committee. In order to 

achieve this, each and every person involved in the drug approval 

process must strictly adhere to the highest standards of conduct 

and maintain an unquestionable level of ethics. 

Unfortunately, from what this committee has learned through its 

year-long investigation of the issues and problems raised by the review and approval of Ketek, it appears that standards of conduct 

and ethics were only optional. Well before the time I arrived here 

in Congress, Chairman Dingell shepherded legislation through this 

House that granted the FDA the power to debar or, essentially, 

blacklist companies and individuals who are convicted of felonies 

for misconduct relating to the regulation of drug products. Individuals who are debarred, or disqualified by the FDA are then listed 

on the FDA Web site. 

Now, it is my understanding that some of the companies testifying here today rely on those lists when selecting physicians to 

serve as investigators in clinical trials, as they rightly should. Debarment is a powerful tool that FDA can use to protect the integrity of the drug approval process, and I applaud Chairman Dingell 

for giving FDA that authority. However, a minority committee staff 

report released yesterday shows that the FDA has failed to initiate 

debarment proceedings against several individuals and companies 

even when the basis for debarment, such as conviction of fraud for 

clinical trial misconduct, clearly exists. By failing to do so, individuals that are currently incarcerated, that are currently sitting in 

jail for felonies they committed, are still eligible to participate in 

administration of clinical trials. This is outrageous. 

When the FDA does pursue debarment, it is in a delayed or perhaps even a lackadaisical manner. According to the staff report, an 

average of 38 months passes between the date of conviction and the 

date that the FDA begins debarment. 

The FDA has a mandate to protect the American people from unsafe drugs and, as such, it must make it a priority to use its authority to immediately ban companies and individuals who are convicted of crimes that could jeopardize the safety of drugs from continuing to do business before the FDA. Both the FDA and the 

drugmakers that are developing new drugs must remain vigilant in 

their efforts to detect and eliminate fraud. 

Hopefully, today’s hearing will help us understand what went 

wrong with Ketek Study 3014 and how we can make sure those 

mistakes and errors never happen again. 

6 

Chairman Stupak, thank you for convening this hearing and 

your diligent work on this issue. And I yield back the balance of 

my time and look forward to hearing from all of our witnesses. 

Mr. STUPAK. I thank the ranking member. 

Mr. STUPAK. I would next call on the chairman of the full committee, Mr. Dingell, for an opening statement, please. 

OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF MICHIGAN 

Mr. DINGELL. Mr. Chairman, thank you for continuing to pursue 

this matter and for your leadership. I commend you for the vigor 

with which you are approaching these matters. 

I would like to remind all and sundry that this is an oversight 

hearing which will be conducted within the traditions and practices 

of this committee. It will be our expectation that all persons called 

upon to participate, either by deliverance of testimony or by presentation of books, papers and records, will cooperate. 

I would remind all and sundry that this is a proceeding which 

is being conducted in a bipartisan fashion; and we will address that 

matter a little further. This committee has, and this subcommittee 

has, a tradition of proceeding to see to it that the business of the 

committee is properly conducted, that all persons cooperate, and 

that they do so in response to a fair and a bipartisan inquiry by 

the committee, aimed at gathering the facts to see whether the law 

is properly enforced and whether or not the Federal officers and 

employees are carrying out their responsibilities in proper fashion. 

We also are looking into seeing whether or not the committee is 

receiving proper information, but also as to whether or not the 

committee will find it necessary to enforce its subpoenas in an appropriate way, looking to the possibility of not only seeing to it that 

the law is properly being enforced and carried out, but as to whether or not additional legislative work by the committee is required 

in order to see to it that the public is properly protected. 

We have here a question relating to the ill-advised approval of 

the antibiotic Ketek. Beyond the harm to the public health from 

millions of prescriptions written on this drug by doctors who relied 

on the FDA, this investigation raises questions about the integrity 

of the drug approval process and those who have engaged in that 

process. 

FDA is supposed to receive clinical data from manufacturers who 

have properly conducted designed studies that prevent serious misconduct or fraud. If FDA knows or suspects such fraud exists and 

then ignores it, then this committee has the duty to probe as deeply as necessary to determine whether the entire approval process 

itself has been compromised. 

Further, this committee expects the full cooperation from Federal 

agencies when we carry out our oversight responsibility to ensure 

that such agencies enforce the laws enacted by the Congress in a 

proper way. 

Given the allegations of wrongdoing in the Ketek matter, we 

have the duty to compel FDA and the Department of Health and 

Human Services to cooperate fully in the inquiries of the comVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00010 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
7 

mittee. Instead, this committee and other committees in the Congress have been repeatedly stonewalled on this matter. 

Our good friend, Senator Grassley, who will be appearing here 

before the committee, the former chairman of the Senate Committee on Finance, who is testifying before us today, initiated inquiries into Ketek during the last Congress. He encountered the 

same bad faith and obstruction from the administration. 

Three of the witnesses today are FDA criminal investigators who 

uncovered the fraud and misconduct that is the subject of our hearing. Unfortunately, the committee had to subpoena them to testify 

at this hearing because Food and Drug Commissioner von 

Eschenbach and Secretary Leavitt refused to allow them to appear 

here voluntarily. A similar refusal thwarted Senator Grassley’s effort in the last Congress. 

This committee will not tolerate actions by the administration 

which would thwart a proper inquiry by this body. It is to be observed that, fortunately, with a bipartisan vote of 12-0 by this subcommittee, we issued subpoenas to these witnesses. 

My good friend, Mr. Joe Barton, the ranking member, and I have 

given the agency every opportunity to avoid this embarrassment, 

but apparently to no avail. Unfortunately, this obstructionist behavior continues. Just yesterday we received a letter from the Secretary’s office, which I ask at this time, Mr. Chairman, be made a 

part of the hearing record. 

Mr. STUPAK. Without objection, Mr. Dingell. 

[The information appears at the conclusion of the hearing.] 

Mr. DINGELL. In that letter, the members of the Secretary’s staff 

announced his refusal to honor the subpoena of the subcommittee 

for records relating to Food and Drug Commissioner von 

Eschenbach’s briefing books. 

I want to remind my colleagues that similar records have been 

turned over to me, as well as to my good friend Mr. Barton, by both 

Republican and Democratic administrations in bipartisan investigations at FDA and other agencies in the executive branch. I 

must also remind all that these records were unanimously subpoenaed by this subcommittee with a bipartisan vote of 12 to nothing. 

I ask my colleagues to then scrutinize Secretary Leavitt’s arguments in refusing to honor the subpoenas of the subcommittee. At 

best, I note they are specious. At worst, they are contemptuous of 

the Congress and of the committee. If anything, the refusal of the 

Secretary to cooperate causes me to wonder, what is the Secretary 

trying to hide? What is in these briefing books that he does not 

want either my Republican colleagues or my Democratic colleagues 

to see? Is there evidence of perjury? Are the statements embarrassing to the Administration? 

In any event, it is the right of this committee to have them, and 

we will do so. Let me make it clear on this point. Neither Chairman Stupak nor I, nor our colleagues of this committee on either 

side will tolerate a perversion of congressional powers to investigate and to probe. I fully support Chairman Stupak’s request to 

enforce this subpoena by holding Secretary Leavitt in contempt. 

Mr. Chairman, there is an easy way for the agency to undergo 

congressional oversight. There is also a hard way. Commissioner 

von Eschenbach and Secretary Leavitt appear to have chosen the 

8 

latter. I caution both gentlemen to reconsider their ill-conceived notion of congressional oversight and to allow the bipartisan policies 

that have long been the practice of this committee to be used for 

the service of the public interest. 

I yield back the balance of my time and I thank you, Mr. Chairman. 

Mr. STUPAK. I thank the gentleman. 

[The prepared statement of Mr. Dingell follows:] 

STATEMENT OF HON. JOHN D. DINGELL

Mr. Chairman, thank you for continuing to pursue the truth regarding the Food 

and Drug Administration’s (FDA) ill-advised approval of the antibiotic Ketek. Beyond the harm to the public health from millions of prescriptions written for this 

drug by doctors who relied on the FDA, this investigation raises questions about the 

very integrity of the drug approval process. 

FDA is supposed to receive clinical trial data from manufacturers who have conducted properly designed studies that prevent serious scientific misconduct or fraud. 

If FDA knows or suspects such fraud and then ignores it, this Committee has every 

reason to probe as deeply as necessary to determine whether the entire approval 

process itself has been compromised. 

Further, this Committee expects the full cooperation from Federal agencies when 

we carry out our oversight responsibility to ensure such agencies enforce the laws 

enacted by Congress. Given the allegations of wrongdoing in the Ketek matter, we 

have every right to expect FDA and the Department of Health and Human Services 

(HHS) to cooperate. 

Instead, this Committee and other committees in Congress have repeatedly been 

stonewalled. Our good friend Senator Grassley, the former Chairman of the Senate 

Committee on Finance, who is testifying before us today, initiated inquiries into 

Ketek during the last Congress. He encountered the same bad faith and obstruction 

from this Administration. 

Three of the witnesses today are FDA criminal investigators who uncovered the 

fraud and misconduct that will be the subject of our hearing. Unfortunately, they 

had to be subpoenaed to testify at this hearing because Food and Drug Commissioner von Eschenbach and Secretary Leavitt refused to allow them to appear here 

voluntarily. A similar refusal thwarted Senator Grassley’s inquiry in the last Congress. Fortunately, with a bipartisan vote of 12-0 by this Subcommittee, we issued 

subpoenas for these witnesses. My friend Joe Barton, the ranking Member, and I 

gave the agency every opportunity to avoid this embarrassment, but to no avail. 

Unfortunately, this obstructionist behavior continues. Just yesterday we received 

a letter from Secretary Leavitt’s office, which I ask to be made part of the hearing 

record. 

In that letter, his minions announced his refusal to honor our subpoena for 

records relating to Food and Drug Commissioner von Eschenbach’s briefing books. 

I must remind my colleagues that similar records have been turned over to me, as 

well as my good friend Joe Barton, by both Republican and Democratic Administrations. I must also remind you that these records were also unanimously subpoenaed 

with a bipartisan vote of 12 to 0. 

I ask my colleagues to analyze Secretary Leavitt’s arguments in refusing to honor 

your subpoena. At best, they are specious. At worse, they border on contempt of 

Congress. If anything, his refusal to cooperate causes me to wonder what he is trying to hide? What is in those briefing books that he does not want either my Republican colleagues or our side to see? Is there evidence of perjury? Are there statements embarrassing to the Administration? 

Let me be clear on this point. Neither Chairman Stupak nor I will tolerate such 

a perversion of congressional powers to investigate and probe. I will fully support 

Chairman Stupak’s request to enforce this subpoena by holding Secretary Leavitt 

in contempt. 

Mr. Chairman, there is an easy way for any agency to undergo congressional oversight. There is also a hard way. Commissioner von Eschenbach and Secretary 

Leavitt appear to have chosen the latter. I caution both gentlemen to reconsider 

their ill-conceived notion of Congressional oversight and follow the bipartisan policies that have long been the practice of this Committee. 

9 

Mr. STUPAK. Mr. Shimkus is delayed because of weather, but 

hopefully he will be here later today. 

Mr. Walden, do you want to make a motion? 

Mr. WALDEN. Mr. Chairman, I have his opening statement that 

I would like to have inserted into the record. 

Mr. STUPAK. Mr. Shimkus’s opening statement will be made a 

part of the record, as will the opening statement of all members of 

the subcommittee. Your statement will be made part of the record 

when they arrive or if they are presented to the committee. 

[The prepared statement of Mr. Shimkus follows:] 

STATEMENT OF HON. JOHN SHIMKUS

Thank you Chairman Stupak for convening this hearing to further examine the 

issues surrounding the antibiotic Ketek (‘‘KEE-tek’’), and how to protect the integrity of the FDA regulatory process. 

Today’s hearing focuses on the conduct of Aventis Pharmaceutical Company, a 

drug company that was the subject of a criminal investigation. In the end, this investigation did not result in a prosecution. 

I think we are all trying to achieve the same thing in this investigation: we want 

a FDA drug review and approval process that promotes and protects the integrity 

of data gathered during clinical trials. But we will never achieve this goal if the individuals and companies who are prosecuted and convicted of crimes for misconduct 

in criminal trials are never debarred by FDA. 

Fifteen years ago, our colleague, Chairman Dingell, spurred the passage of the 

Generic Drug Enforcement Act. Through that Act, Congress gave FDA the power 

to debar companies and individuals who are convicted of felonies for misconduct relating to the regulation of drug products. Individuals who are debarred or disqualified by FDA are then listed on the FDA website. It is my understanding that some 

of the companies testifying here today rely on those lists when selecting physicians 

as investigators in clinical trials. 

However, as a report prepared by Minority Committee Staff and released yesterday shows, FDA.has failed to initiate debarment proceedings against several individuals and some companies even when the basis for debarment clearly exists. It 

has also initiated debarments in an uneven way; the Staff Report cites more than 

one example where FDA pursued debarment in one case, but did nothing in another 

case where the underlying facts and convictions were similar. FDA also takes years 

to initiate debarment proceedings after conviction; according to the staff report, an 

average of 38 months passes between the date of conviction, and the date FDA begins debarment. The delay has very real consequences for public health, as an investigator convicted of a felony relating to clinical trial misconduct can continue to receive investigational drug products and participate in trials up to the date debarment is finally imposed. 

As we now know, Dr. Kirkman-Campbell, one of the investigators in the Ketek 

trial, was indicted on fraud charges for her misconduct in Study 3014. During our 

investigation of Ketek, Minority Committee staff learned that, despite the fact that 

Kirkman-Campbell had been convicted of a felony and incarcerated in federal prison, FDA had never debarred her. In fact, sheis still not debarred today, even though 

FDA initiated debarment proceedings against her almost one year ago. This means 

that under federal law, she is still eligible to participate in clinical trials, even 

though she is currently incarcerated. 

We should not be surprised when there is a lack of vigilance and awareness of 

fraud when the industry’s regulator does not make it a priority to ban companies 

and individuals who are convicted of crimes from continuing to do business before 

FDA. We need to have a system in whichpharmaceutical companies and clinical 

trial patients can have confidence. For this reason, Ranking Member Barton will 

pursue legislation that strengthens FDA’s debarment authority. Under this legislation, FDA will have authority over not only generic drug companies, but any 

companydoing business before FDA. The Act will also clarify that FDA will have authority to debar companies not just’for their misconduct relating to the development 

and approval of a drug application, but any misconduct relating to the regulation 

of the drug. We should hold companies and individuals who do business before FDA 

to the same standard, without respect to thetype of drug product. I look forward to 

providing Ranking Member Barton with whatever assistance I can to help with this 

important bill. I hope my colleagues on this Committee will do the same. 

10 

I am looking forward to the testimony from the companies involved in the Ketek 

safety trial: Dr. Paul Chew for Aventis, the sponsor; Dr. Fred Eshelman, of PPD, 

the study monitor; and Sharon Hill Price from Copernicus, the institutional review 

board. I expect that each of these witnesses will provide a candid assessment of 

their work during the trial; the procedures they had in place to detect and identify 

fraud; and how they dealt with concerns about fraud. Hindsight is always twentytwenty. But even cursory review of the monitoring reports and emails exchanged 

among the parties during Study 3014 shows that the parties were aware that fraud 

was apossibility as early as January 2002—a full seven months before Aventis submitted the results of the study to FDA. 

We want to know why Aventis felt it was appropriate to include data from Dr. 

Kirkman-Campbell’s site, as well as other sites where the suspicion of fraud was 

raised, in its July 2002 report on Study 3014 without noting the number of Good 

Clinical Practice violations and protocol violations. I understand that Study 3014 

was a safety study, and that the point of thestudy was to collect as much data as 

possible on adverse events related to Ketek. However, in a case such as this where 

Clinical Practice Violations, fraud allegations, and other violations exist to a degree 

that may affect data integrity, at what point should a company begin to question 

the safety data? I would also like a better understanding of the roles of the study 

monitor, PPD, and the institutional review board, or IRB, Copernicus, in selecting 

thephysicians who participate in the study and dealing with the problems and violations that presented during the study. 

We are also joined today by the FDA criminal investigators who were assigned 

to investigate the allegations of fraud in Study 3014: Robert West, Robert Ekey, and 

Douglas Loveland. Two weeks ago, the Republicans on this Subcommittee supported 

Chairman Stupak’s motion to subpoena the testimony of these criminal investigators. As the investigators who have interviewed the major players in the Ketek safety trials, your testimony is critical to helping us have the best possible understanding of the evidence in this case. 

Finally, I would like to thank Senator Chuck Grassley, for taking the time to be 

with us this morning. Senator Grassley has been investigating the Ketek safety 

trials and FDA’s review and approval of Ketek for the last three years. I look forward to his testimony. 

Hopefully, today’s hearing will help us understand what went wrong in Study 

3014; whether those mistakes and errors could have been prevented; and how we 

can make sure they never happen again. 

I thank Chairman Stupak for convening this hearing and yield back the balance 

of my time. 

Mr. STUPAK. Mr. Burgess for an opening statement, please. 

OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A 

REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS 

Dr. BURGESS. Thank you, Mr. Chairman. Mr. Chairman, I want 

to apologize in advance because I do have to leave this hearing 

early. Congress doesn’t vote until much later this afternoon, but 

when this hearing was scheduled, I had made previous plans to 

travel to another key Federal agency over which this committee 

also has oversight. 

But I do believe this is an important hearing, and I only wish 

it had been scheduled when there was availability for more members to attend. 

Today, we are here to continue our discussion regarding the approval process for the antibiotic Ketek. When I was practicing medicine for over 20 years, my patients relied on me to administer safe 

medicine. In return, I relied upon the Federal drug approval process. I relied on the process to be prudent and cautious. I relied on 

the notion that the approved drugs were safe. However, when there 

is a breakdown in the process, and when there are fraudulent activities, this reliance can prove dangerous. 

11 

As a physician, it is unfathomable that anyone would gamble 

with my patients’ lives. I believe that any allegation of wrongdoing 

must be seriously investigated. 

It is important to note that the largest enroller of Ketek, Dr. 

Kirkman-Campbell, is now serving 4 years in Federal prison for 

her wrongdoings. I think it is important also to note and to thank 

the leadership of this committee, as well as the leadership of Senator Grassley, for their pursuit of truth in Ketek’s approval process. It is my hope that this investigation is able to shed some light 

on troublesome allegations, and that we never again have to learn 

of another Study 3014 and, more importantly, that the confidence 

of America’s doctors and America’s patients and America’s mothers 

and fathers are not further undermined. 

There are still many questions that need to be answered, and I 

am hopeful that the witnesses testifying before us today, including 

the FDA criminal investigators, as well as the companies involved 

in the approval process of this drug, will be able to address many 

of the allegations before the committee. 

While, clearly, the focus of this hearing is on Ketek, I would be 

remiss if I did not also briefly mention the minority staff report 

that was issued yesterday, detailing the problems with the FDA’s 

debarment process. The report also makes some serious allegations, 

including the troubling fact that Dr. Kirkman-Campbell, now a convicted felon, is still eligible to work with the FDA because she has 

not been debarred. According to Ranking Member Joe Barton, who 

issued the report, quote, ‘‘When it comes to excluding the worst of 

the worst, convicted felons, the Food and Drug Administration’s debarment process seems to be nonexistent,’’ end quote. 

Now, the staff-prepared minority report does disclose an ongoing 

pattern of inaction and, perhaps, an almost institutional nonenforcement regarding the debarment proceedings. And this subcommittee, appropriately, is holding hearings. But, Mr. Chairman, 

I do have to say it seems like we are holding hearing upon hearing. 

We are now 13 months or more into this process—apparently, 

some of the problems go back at least as far as 15 or 16 years— 

and I do have to ask the question, When are we going to get to the 

point where we actually legislate on this issue and stop just endless investigation after investigation? 

This is the type of product that America—America’s doctors, 

America’s patients, America’s moms and dads—want to see out of 

this committee, indeed, what they have come to expect. 

I also feel it is my obligation to mention that we are now 65 

years into the availability of antibiotics for treating infectious disease. Antibiotics have changed the practice of medicine. 

Not every antibiotic that is out there is without risk. For example, penicillin, one of the early antibiotics to be introduced back in 

the early 1940s, would have a difficult time with the approval process today. I am allergic to penicillin; there is a chance I could die 

if I took that medication. Yet I am grateful that that medication 

exists. 

As someone who is allergic to penicillin, I am also grateful that 

there is ongoing research and development of antibiotics to treat 

community-acquired pneumonia for individuals who are allergic to 

penicillin. And Ketek would fall into that category. 

12 

Other antibiotics that had been introduced, that had serious side 

effects, such as chloramphenicol, are now available to treat the 

most serious of infections; and it would be a mistake—it would be 

a mistake if those antibiotics were not still available. So we do 

have to balance what is in the broad public interest as we continue 

our efforts at oversight, to make certain that the FDA does indeed 

provide the level of commitment that we all wish it would. 

Now, this committee has jurisdiction over the FDA. We have a 

duty to the public to review and investigate this problem and to 

legislate solutions for this problem. And I thank Ranking Member 

Barton for having the minority staff report prepared and bringing 

this to our attention; and I hope we can work in a bipartisan manner to investigate and resolve this issue. 

Mr. Chairman, in the interests of time, I will yield back the balance of my time. 

Mr. STUPAK. Thank you, Mr. Burgess. 

Mr. STUPAK. Seeing no other members, we will begin with our 

panel of witnesses. 

On our first panel to come forward today we have Ms. Ann Marie 

Cisneros, former Senior Clinical Research Associate at PPD, Inc.; 

Mr. Robert West, Special Agent in the Office of Criminal Investigation at the Food and Drug Administration; Mr. Robert Ekey, Assistant to the Special Agent in Charge at the Special Investigations 

Division, Office of Inspector General at the Department of Housing 

and Urban Development—that’s a long title—and Mr. Douglas 

Loveland, Special Agent in the Office of Criminal Investigation at 

the Food and Drug Administration. 

Welcome, all. 

It is the policy of this subcommittee to take all testimony under 

oath. Please be advised that witnesses have the right under the 

rules of the House to be advised by counsel during testimony. 

Do any of you wish to be represented by counsel today? 

All witnesses are indicating they do not. 

Therefore, I am going to ask you to please rise and raise your 

right hand and take the oath. 

[Witnesses sworn.] 

Mr. STUPAK. Let the record reflect that the witnesses replied in 

the affirmative. 

You are now under oath. We will now hear a 5-minute opening 

statement from this panel. You may submit a longer statement for 

the record. Your statement will be part of the record. 

Mr. STUPAK. Ms. Cisneros, we will start with you, please, if you 

would. 

STATEMENT OF ANN MARIE CISNEROS, FORMER SENIOR 

CLINICAL RESEARCH ASSOCIATE, PPD, INC. 

Ms. CISNEROS. Good morning, Mr. Chairman and members of the 

committee. I am honored that you are giving—— 

Mr. STUPAK. Would you pull that mike a little closer? 

Ms. CISNEROS. Sure. 

I am honored you are giving me the opportunity to tell my story. 

My name is Ann Marie Cisneros. I am currently an independent 

clinical research associate. I served in the U.S. Air Force as a Medical Technologist, have a Bachelor of Science degree in OccupaVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00016 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
13 

tional Education, Wayland Baptist University, and an MBA from 

Pfieffer University. 

I have worked as a clinical research associate for approximately 

8 years. My first 3 years in the industry I spent at PPDI, a contract research organization, where I monitored a number of protocols that included the large Ketek study, called Study 3014. At the 

time of the Study 3014, I was a senior clinical research associate 

and was tasked to assist with the monitoring of Dr. Ann KirkmanCampbell’s site. 

Dr. Campbell is currently serving a 57-month prison sentence for 

fraud associated with Study 3014. In addition, she was ordered by 

the court to pay restitution to the drug sponsor Aventis, which had 

paid her $400 per patient enrolled. 

Mr. Chairman, based upon what I observed and learned in monitoring the Kirkman-Campbell site, Dr. Campbell indeed had engaged in fraud. But what the court that sentenced her did not 

know is that Aventis was not a victim of this fraud. On the contrary, let me explain. 

Even before conducting the Kirkman-Campbell site visit, a number of red flags were apparent. I knew that Dr. Campbell had enrolled over 400 patients, or 1 percent of the adult population of 

Gadsden, Alabama. By comparison, another site in Gadsden had 

enrolled only 12 patients. 

In a quality assurance audit by Aventis in early 2002, several informed consent issues were noted, as well as a significant underreporting of adverse events and no reports of serious adverse 

events. No patients had withdrawn from the study, and no patients 

were lost to follow-up, an unusual occurrence given the number of 

subjects. 

She enrolled patients within minutes of each other, and upwards 

of 30 a day. She enrolled patients at times and on days when her 

office was closed. 

Once we started reviewing patient charts, we discovered that 

every informed consent had a discrepancy. Most of the consents 

looked like they had been initialed by someone other than the patient. A lot of the consents were dated by someone other than the 

subject. One consent was a blatant forgery. 

There were date discrepancies as to when patients were enrolled 

in the study, had blood drawn, or had signed consent. Most patients diagnosed with bronchitis either had no history of the ailment or did not have a chronic condition. 

She enrolled her entire staff in the study. Frankly, all KirkmanCampbell seemed truly interested in was getting more business 

from Aventis as an investigator. At one point during my site visit, 

she told Aventis Project Manager Nadine Grethe that I could only 

stay if Nadine got her other studies at Aventis. Nadine must have 

agreed, because it is my understanding that when FDA audited the 

Kirkman-Campbell site, she was indeed participating in another 

Aventis clinical trial. 

While at the site, I was so concerned about patient safety, I 

called Copernicus Independent Review Board or IRB to express my 

concerns and seek guidance. An IRB, which is under contract to the 

drug sponsor, has as its primary purpose patient advocacy. It is allowed to contact patients directly and is duty-bound to report to the 

14 

FDA any unanticipated problems involving risk to subjects and serious noncompliance with regulations. 

I spoke with someone, who I understood to be the president of 

the company, and was told that while she shared my concerns, she 

preferred to wait and see what actions Aventis took. I never did 

hear from the IRB again, and to my knowledge, Copernicus never 

did audit or blacklist the site, or report any irregularities to the 

FDA. 

I e-mailed a summary of my site visit findings to Robert McCormick, head of quality assurance at PPD, and copied Aventis personnel. I also participated in a teleconference between PPD and 

Aventis, at which I discussed issues identified in my site visit. 

At some point after that, I understand that Aventis took site 

management responsibilities away from PPD because Dr. Campbell 

would not cooperate with anyone but the sponsor. 

I subsequently left PPD, but learned that the Kirkman-Campbell 

site was being audited by the FDA. In preparation for the audit, 

I was told by a trusted and distressed former colleague at PPD that 

Nadine Grethe coached Dr. Campbell on how to explain away some 

of the site irregularities. 

I was called on two occasions by PPD lawyers who reminded me 

of the confidentiality agreement I signed, and advised me not to 

speak with the FDA without Aventis approval and PPD attorneys 

present. 

In my 8 years in clinical research work, this is the only instance 

I have come across of such abysmal behavior by a drug sponsor. I 

feel I can speak for those who agonized over the situation when I 

say we are pleased that Dr. Campbell is serving prison time for her 

actions, though what brings me here today is my disbelief in 

Aventis’ statements that it did not suspect that fraud was being 

committed. 

Mr. Chairman, I knew it. PPD knew it. And Aventis knew it. 

Thank you. 

Mr. STUPAK. Thank you. 

[The prepared statement of Ms. Cisneros follows:] 

STATEMENT OF ANN MARIE CISNEROS

Good morning Mr. Chairman and members of the Committee. I am honored that 

you are giving me the opportunity to tell my story. 

My name is Ann Marie Cisneros, I am currently an independent clinical research 

associate. I served in the United States Air Force as a Medical Technologist, have 

a Bachelors of Science Degree in Occupational Education from Wayland Baptist 

University and a Masters of Business Administration Degree from Pfieffer University. 

I have worked as a clinical research associate for approximately eight years. My 

first three years in this industry I spent at PPDI, a Contract Research Organization, 

where I monitored a number of protocols that included the large Ketek study called 

Study 3014. At the time of Study 3014, I was a senior clinical research associate 

and was tasked to assist with the monitoring of Dr. Anne Kirkman-Campbell’s site. 

Dr. Kirkman-Campbell is currently serving a 57-month prison sentence for fraud 

associated with Study 3014. In addition she was ordered by the court to pay restitution to the drug sponsor, Aventis, which had paid her $400 per patient enrolled. 

Mr. Chairman, based upon what I observed and learned in monitoring the 

Kirkman-Campbell site, Dr. Kirkman-Campbell indeed had engaged in fraud. But 

what the court that sentenced her did not know is that Aventis was not a victim 

of this fraud. On the contrary. Let me explain. 

Even before conducting the Kirkman-Campbell site visit, a number of ‘‘red flags’’ 

were apparent. I knew that Dr. Kirkman-Campbell had enrolled over 400 patients 

15 

or 1% of the adult population of Gadsden, Alabama. (By comparison, another site 

in Gadsden had enrolled just twelve patients.) In a Quality Assurance audit by 

Aventis in early 2002 several Informed Consent issues were noted as well as a significant under-reporting of Adverse Events and no reports of Serious Adverse 

Events. No patients had withdrawn from the study and no patients were lost to follow up, an unusual occurrence given the number of subjects. She enrolled patients 

within minutes of each other and upwards of 30 patients per day. She enrolled patients at times and on days when the office was closed. 

Once we started reviewing patient charts, we discovered that: 

• Every informed consent had a discrepancy. 

• Most of the consents looked like they had been initialed by someone other than 

the patient. • A lot of the consents were dated by someone other than the subject. 

• One consent was blatantly forged. 

•There were date discrepancies as to when patients were enrolled in the study, 

had their blood drawn or signed their consent. • Most patients diagnosed with bronchitis either had no history of the ailment or 

did not have a ‘‘chronic’’ condition. • She enrolled her entire staff in the study. 

Frankly, all Kirkman-Campbell seemed truly interested in was getting more business from Aventis as an investigator. At one point during my site visit, she told 

Aventis Project Manager Nadine Grethe that I could only stay if Nadine got her 

other studies at Aventis. Nadine must have agreed. It is my understanding that 

when the FDA audited the Kirkman-Campbell site, she was participating in another 

Aventis clinical trial. 

While at the site, I was so concerned about patient safety I called Copernicus 

Independent Review Board or IRB to express my concerns and seek guidance. An 

IRB, which is under contract to the drug sponsor, has as its primary purpose patient 

advocacy. It is allowed to contact patients directly and is duty-bound to report to 

the FDA any unanticipated problems involving risks to subjects and serious noncompliance with regulations. I spoke with someone who I understood to be the president of the company and was told that, while she shared my concerns, she preferred 

to wait and see what actions Aventis took. I never heard from the IRB again. To 

my knowledge Copernicus never did audit or blacklist the site, or report any irregularities to the FDA. 

I e-mailed a summary of my site visit findings to Robert McCormick, head of quality assurance at PPD, and copied Aventis personnel. I also participated in a teleconference between PPD and Aventis at which I discussed issues identified in my 

site visit. At some point after that I understand that Aventis took site management 

responsibilities away from PPD because Dr. Kirkman-Campbell would not cooperate 

with anyone but the sponsor. 

I subsequently left PPD but learned that the Kirkman-Campbell site was being 

audited by the FDA. In preparation for the audit, I was told by a trusted and distressed former colleague at PPD that Nadine Grethe, Proect Manager at Aventis 

coached Dr. Kirkman-Campbell on how to explain away some the site irregularities. 

I was called on two occasions by PPD lawyers who reminded me of the confidentiality agreement I signed and advised me not to speak with the FDA without 

Aventis approval and PPD attorney’s present. 

In my eight years in clinical research work, this is the only instance I’ve come 

across of such abysmal behavior by a drug sponsor. I feel I can speak for those who 

agonized over this situation when I say we are pleased that Dr. Kirkman-Campbell 

is serving prison time for her actions. But what brings me here today is my disbelief 

at Aventis’s statements that it did not suspect that fraud was being committed. Mr. 

Chairman, I knew it, PPD knew it, and Aventis knew it. 

Thank you for this opportunity to tell my story. 

Mr. STUPAK. Do either of—the special agents, my understanding, 

do not want to make a statement. 

Do you wish to say anything? 

Mr. West. 

Mr. WEST. Mr. Chairman, I don’t have an opening statement. 

Mr. STUPAK. Mr. Ekey? 

Mr. EKEY. No, sir. 

Mr. STUPAK. No, Mr. Loveland? 

Mr. LOVELAND. No, sir. 

16 

Mr. STUPAK. OK, then we will go right to questions. 

Ms. Cisneros, if I may, you indicated that after a couple days you 

called the IRB, Copernicus. 

Ms. CISNEROS. Yes, sir. 

Mr. STUPAK. Do you know when that was? 

Ms. CISNEROS. It was probably 3 or 4 days into my visit, so either a Wednesday or a Thursday. I believe it was Wednesday of 

that week. 

Mr. STUPAK. OK. Why did you call Copernicus? 

Ms. CISNEROS. I knew fraud was being committed at the site, 

and I feared for patient safety. While I wanted to go up the chain 

of command at PPD, I just felt like Copernicus could take immediate action against the site. 

Mr. STUPAK. Their responsibility is the patient safety? 

Ms. CISNEROS. Correct. 

Mr. STUPAK. Is that their main focus in a clinical trial, an IRB, 

institutional review board? 

Ms. CISNEROS. Well, their main focus is approving informed consents and protocols that reflect patient safety, or to ensure patients 

are kept safe. But there was a statement in the informed consent 

that said the patients could call the IRB if they had any concerns. 

Mr. STUPAK. Sure. So any concerns about patient safety should 

be directed to the IRB, then? 

Ms. CISNEROS. Correct. 

Now monitors aren’t ever encouraged to call IRBs. There is just 

not a relationship there. So just to put that in the record. 

Mr. STUPAK. So this was unusual for you to do this? 

Ms. CISNEROS. Absolutely, yes. 

Mr. STUPAK. But you felt compelled to call Copernicus? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. How did you—by telephone, I take it? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. Do you know who you called? 

Ms. CISNEROS. I believe it was the president of the company at 

the time. 

Mr. STUPAK. OK. Right in front of Mr. Ekey there, could you 

could hand her that big binder? 

Would you please take a look at Exhibit No. 4? 

Ms. CISNEROS. I am sorry, what number? 

Mr. STUPAK. No. 4, please. 

Ms. CISNEROS. All right. 

Mr. STUPAK. OK. Exhibit 4 has two pages. 

And while you are holding that tab, would you also go to Exhibit 

33? I want to direct you to those two documents, 33 and 34—33 

and No. 4, excuse me. 

Could you identify number 33 for us? 

Ms. CISNEROS. 33 is a telephone contact report taken by the IRB 

of my phone call. 

Mr. STUPAK. OK. And it is dated February 21, 2002? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. OK. This says IRB staff member taking call, Sarah 

Wallace. 

Do you know who Sarah Wallace is. 

Ms. CISNEROS. I don’t recollect that name. 

17 

Mr. STUPAK. OK. Do you know if she is the president of Copernicus? 

Ms. CISNEROS. To my knowledge, Sharon Hill Price was the 

president of Copernicus. 

Mr. STUPAK. OK. Do you know Ms. Price? 

Ms. CISNEROS. I do not, no. 

Mr. STUPAK. OK. But it is your recollection that that’s who you 

spoke to on that day? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. OK. And does the—it says in here ‘‘she,’’ meaning 

you, has reviewed 50 of the 400 files, and some of her concerns are 

listed below. Do those accurately reflect your concerns? 

Ms. CISNEROS. Yes, they do. 

But I also remember saying that I was willing to furnish the IRB 

with patient names and phone numbers of patients I thought to be 

fraudulent in an effort to, again, have some validity as to whether 

these patients were actually true patients or not. I don’t see that 

noted in this. 

Mr. STUPAK. OK. Did the president of Copernicus then ask you 

for those names or numbers of these patients? 

Ms. CISNEROS. No. 

Mr. STUPAK. OK. Let me go to Exhibit No. 4, second page. 

Again, would you please review the second page? Does that reflect any of the statements you may have made to Copernicus? 

Ms. CISNEROS. I didn’t go into detail about each subject. I pretty 

much said, every informed consent had an issue, and that one consent I believed to be a forgery. I didn’t know what she was doing 

with the study drug, if patients were being given the drug and then 

not followed, that sort of thing. 

So, no, I didn’t go into specifics. 

Mr. STUPAK. OK. On page 1 of that Exhibit 4, it says—it is from 

a Jessica Lasley—— 

Ms. CISNEROS. Uh-huh. 

Mr. STUPAK [continuing]. And you are carbon-copied on this. And 

this was a telephone conference to discuss findings from monitoring 

of Kirkman-Campbell; is that correct? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. This was a few days after you made the call on February 27, 2002? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. Were you in on that conference call? 

Ms. CISNEROS. Yes, I was, if it is the one—there was one teleconference that I was in on. 

Mr. STUPAK. And do you believe this was the one then? 

You are listed there as—carbon copy was sent to a Nadine 

Grethe and then carbon-copied to you. 

Ms. CISNEROS. Yeah. This is an e-mail setting up the teleconference. So I participated in that teleconference, yeah. 

Mr. STUPAK. Down at the bottom it says Ann Marie—that would 

be you? 

Ms. CISNEROS. Yes. 

Mr. STUPAK. And John have assembled some examples of this information we can share with you. Let us know. We have attached 

a summary of Ann Marie’s findings during her visit. 

18 

Ms. CISNEROS. Correct. 

Mr. STUPAK. OK. My time is up. I am going to want to come back 

to this witness. And let me just ask one question then, one more 

question. 

Did Dr. Kirkman-Campbell react to you monitoring her site? Did 

she try to get rid of you during the course of your investigation. 

Ms. CISNEROS. Well, she was very uncomfortable with us being 

there. She constantly complained about how we were taking up 

space in her office. She couldn’t see as many patients as she wanted to, that sort of thing. 

After—I believe it was Thursday of that week, she was going to 

send me home; and I was in her office, and she was on a teleconference—or she was talking to Nadine Grethe. And I heard her say, 

Nadine, I will let Ann Marie stay if you can get me into more 

Aventis studies. 

Mr. STUPAK. So the Nadine that she was talking to was Nadine 

Grethe from Aventis? 

Ms. CISNEROS. Correct. 

Mr. STUPAK. And that is the same Nadine that is in Exhibit 4 

that you had this telephone conference with on Wednesday, then, 

of that week that you were down there? 

Ms. CISNEROS. Correct. 

Mr. STUPAK. And the next day—on Thursday did you leave then, 

Dr. Kirkman-Campbell’s office? 

Ms. CISNEROS. I believe I left that day, yes. 

Mr. STUPAK. Thank you. 

Mr. Walden for questions then, please. 

Mr. WALDEN. Thank you, Mr. Chairman. 

Ms. Cisneros, you participated in that conference call with 

Aventis in March of 2002 to discuss concerns with Dr. KirkmanCampbell’s site, correct? 

Ms. CISNEROS. Correct. 

Mr. WALDEN. And what follow-up did Aventis decide to do to address PPD’s concerns? 

Ms. CISNEROS. Well, unfortunately, I left PPD shortly after that 

teleconference, so I am not quite sure what took place after that 

teleconference. 

Mr. WALDEN. OK. 

At the time of the call did you believe this follow-up was appropriate? But if you have left, then— 

Ms. CISNEROS. No, I just remember from the teleconference how 

laissez-faire Aventis personnel were about the study findings and 

the excuses they provided for some of the oddities at the sites. It 

was very frustrating, because they didn’t seem to want to acknowledge fraud in the least. 

Mr. WALDEN. Do you believe Aventis intentionally ignored evidence of fraud? Or is it a matter that their processes and procedures for verifying fraud were faulty and couldn’t have detected it? 

Ms. CISNEROS. I personally believe they ignored evidence of 

fraud. You had to have your head stuck in the sand to have missed 

this. 

Mr. WALDEN. Agent Loveland, if I could address a question to 

you—you may want to pull that mike fairly close—what do you 

think about their follow-up procedures? 

19 

Mr. LOVELAND. It is a catastrophic failure. 

Mr. WALDEN. In what respect? 

Mr. LOVELAND. The decision-making process that Aventis used to 

evaluate the warnings that Mrs. Cisneros and other PPD folks 

raised was illogical, ineffective. And it could have led them to not 

come to the proper conclusion; it was that bad. 

Mr. WALDEN. Do you think that that process and procedure is in 

place and used in other drug evaluations? Have you seen any evidence of that? 

Mr. LOVELAND. I don’t know. I have seen other divisions of 

Aventis run clinical trials in other ways, and it was not this bad. 

Mr. WALDEN. What makes this unique? 

Mr. LOVELAND. From start to finish, their process for analyzing 

information coming out of the trial was poor. 

When you get into a traffic accident, you call a traffic cop. These 

folks came in and they said, We have indicators of fraud, and they 

called a mathematician. 

A mathematician didn’t know what fraud looked like, and he 

couldn’t identify it. He looked at all the data, couldn’t figure out 

a rule to apply to the data set, came back and said, I don’t see 

fraud. They took that to convince themselves that two of the most 

serious allegations raised by Ms. Cisneros and by other PPD folks 

weren’t indicators of fraud. 

The next thing they did was, they said, Well, let’s take a look at 

all these uses of different-colored inks and the cross-outs and all 

the other things that teach us these are red flags when you see 

these in clinical trials. And they decided to fix them with a blizzard 

of memos to file that get filed with the IRB long after the patients 

were even enrolled. 

Mr. WALDEN. Explain what you mean by that. 

When you say ‘‘memos to file’’ and ‘‘a blizzard’’ of them, what 

were they saying in those memos? 

Mr. LOVELAND. Essentially, that the monitors or the auditors had 

found these problems in each informed consent or in each medical 

record; the clinical investigator—in this case, Kirkman-Campbell— 

was reeducated or trained on how to do this right. 

She signed the memo to file; and it was forwarded to the IRB, 

as though that had some sort of rehabilitative effect, and it didn’t. 

In fact, the trial had stopped enrolling 2 months earlier. There is 

absolutely nothing the IRB could have done with them. 

And the final serious allegation, which they held to the very end, 

that just fell off the radar—it was the allegation of forgery. 

Mr. WALDEN. Have you found any evidence that this was intentional on Aventis’ part? Or is it just sloppy? Or is it head-in-thesand? 

Mr. LOVELAND. It is interesting you would use the word ‘‘sloppy.’’ 

That’s how they described Kirkman-Campbell. And the problem is 

not so much that it is—was it fraud or was it sloppy. We want reliable data at the FDA. 

Mr. WALDEN. Sure. 

Mr. LOVELAND. Whether it is fraud or sloppy, it is not reliable. 

Mr. WALDEN. Understood. 

20 

Mr. LOVELAND. Their threshold was, they had to find fraud. Before they would not submit it to the agency, which leads me to believe they were willing to submit sloppy data. 

That is a flawed decision-making process. 

Mr. WALDEN. At Aventis or at—— 

Mr. LOVELAND. At Aventis. 

Mr. WALDEN. OK. If you suspected Aventis intentionally designed a system to not let itself know or be able to detect criminal 

fraud, what evidence would you seek to substantiate that suspicion? 

Mr. LOVELAND. Well—— 

Mr. WALDEN. And was such evidence sought? 

Mr. LOVELAND. Mr. West ran a great case with respect to Dr. 

Kirkman-Campbell. 

Mr. WALDEN. Right. 

Mr. LOVELAND. He proved in his investigation that falsified data 

was created. 

Mr. WALDEN. Got it. 

Mr. LOVELAND. Mr. Ekey did a great job during the 9 months he 

had the case of solidifying the complaint, making sure that he had 

all the complaining documents, that the data that were falsified 

were submitted to Aventis, and Aventis submitted them to the 

FDA. 

So when I came in, all I had to do was figure out whether or not 

Aventis knew on the day they submitted the data that the data 

had been falsified. That was the only question left for me to answer. 

Mr. WALDEN. And the answer was? 

Mr. LOVELAND. I can’t prove that beyond a reasonable doubt, and 

that’s the standard I have to eventually meet in court. I only have 

one institution of resolution. It is the U.S. court system, and that 

is the standard I have to meet. 

Unable to meet that, we refer it back to the FDA for regulatory 

action. 

Mr. WALDEN. And you weren’t able to meet that because of all 

the memos to file: that they had identified this, they had attributed 

it to a sloppy process, they reeducated the doctor, and so, therefore, 

because they admitted to all those things and had their memos to 

file—— 

Mr. LOVELAND. They actually took a number of steps. They had 

a meeting under their fraud SOP. They didn’t do it very well, but 

they had one. 

They had a plan. They didn’t follow it real well, and the plan 

wasn’t terribly effective, but they had one. They could individually 

answer every single allegation. 

Collectively, you can look at it from 30,000 feet and show that 

it just didn’t work, but they could individually answer each one. 

And what I described to you, sir, is more than reasonable doubt in 

the mind of a jury, and so at the end of the day, I would have 

failed in my only institution of resolution. 

Mr. WALDEN. Could you briefly address the issue of debarment? 

Mr. LOVELAND. No, sir. I don’t know anything about it. That is 

a different part of the FDA. 

Mr. WALDEN. All right. 

21 

Thank you, Mr. Chairman. 

Mr. STUPAK. Thank you, Mr. Walden. 

Mr. Burgess for questions, please. 

Dr. BURGESS. Thank you, Mr. Chairman. Let me ask any of the 

three investigators who would like to answer this: Is this an unusual situation? Have you investigated other companies for this 

type of allegation, and could you give us an idea as to how many 

companies have undergone such investigation? 

Mr. WEST. Well, I can address what I have done in my 11 years. 

It is not normally the company that we are investigating; it is normally the PI who is conducting the clinical trial that we investigate. 

Dr. BURGESS. So this was unusual in that it—— 

Mr. WEST. This is unusual, yes, in my experience. 

Mr. LOVELAND. Those kinds of cases are actually handled by my 

unit. And this is not a very common type of an offense, where we 

have a major pharmaceutical corporation who has been accused of 

submitting intentionally falsified data. 

That is not unheard of, but it is not terribly common. 

Dr. BURGESS. But there have been other cases? 

Mr. LOVELAND. I believe so. 

Dr. BURGESS. And in those cases what did the fraud look like? 

Mr. LOVELAND. The ones I am familiar with, it is dry-labbing, it 

is making up data. 

In one case I ran a case where one company stole another company’s data and submitted it. But these are not typically large companies like Aventis was. 

Dr. BURGESS. So there is not really an established pattern that 

someone could rely on when a company—or when there is a suspicion that a company is involved; is that correct? 

Mr. LOVELAND. This did not fit any pattern I have seen before, 

sir. 

Dr. BURGESS. Then how did the company itself react to when you 

brought forth the issues that you have discussed with Mr. Walden? 

Mr. LOVELAND. At the beginning of the week, they were very cooperative, very friendly, very warm, very hospitable. They pledged 

that they just had—they didn’t believe it was fraud, they didn’t see 

fraud during the conduct of the trial. They thought everything was 

OK, and they would be happy to make anything available to me 

that I wanted. 

By the end of the week, they were saying, Gee, we have learned 

an awful lot here this week, because they sat in on all of the interviews. 

Dr. BURGESS. So they learned a lot in the process of following 

you through your investigation? 

Mr. LOVELAND. Well, they learned a lot that week, I believe. 

Dr. BURGESS. Well, was the kind of fraud that took place with 

Dr. Kirkman-Campbell, was it unusual in your experience for the 

pattern of fraud in a clinical study? 

Mr. LOVELAND. It is very typical type of PI-level fraud, making 

up patients. The only thing that was different here was, KirkmanCampbell used actual patients with actual files. And in doing that, 

that does make it a little bit harder to detect, because when you 

22 

just completely make a patient up out of whole cloth there are 

some indicators in the patient’s file that you can see—— 

Dr. BURGESS. But surely a big company like Aventis that is in 

the practice of doing these types of investigations, if there is a 

graphite titration, they should be able to pick that up, correct? 

Mr. LOVELAND. They hire PPD to pick it up, and PPD picked it 

up. PPD sent signals to Aventis. They were loud signals, they were 

bright signals, and they were repetitive signals. Aventis should 

have known. 

Dr. BURGESS. Well, in addition to the site that is under—that we 

are focusing on today, was there fraud at other sites as well? 

Mr. LOVELAND. I believe there was. 

Dr. BURGESS. Was that unusual, to find that there was this level 

of fraud at more than one site? 

Mr. LOVELAND. No. When you have 1,826 ‘‘anybodies’’ put together, you are going to have an offender in the mix. You are going 

to have more than one offender. There are criminological studies 

out there that show this. 

Dr. BURGESS. So this level was not unusual—or it was unusual? 

Mr. LOVELAND. Eighteen hundred clinical investigators in one 

study is more than I have ever seen before. But what you have to 

have is a robust fraud detection and neutralization program to protect your clinical trial from the fraud and to preserve the sanctity 

of your data’s integrity. 

Dr. BURGESS. But could the company have anticipated this degree of misbehavior on the part of their investigators? 

Mr. LOVELAND. They should have. 

Dr. BURGESS. Do you think the level of fraud found in this Study 

3014 is a function of having such a large study? 

Mr. LOVELAND. That magnified it. 

Dr. BURGESS. Was it the way in which the investigators themselves were selected? 

Mr. LOVELAND. I am sorry, sir? 

Dr. BURGESS. Did it in any way reflect on how the investigators 

were selected, how they were trained? 

Mr. LOVELAND. I didn’t look into that, and I wouldn’t feel comfortable commenting on that. 

Dr. BURGESS. In your opinion, would it be a lack of vigilance by 

the company in identifying and detecting fraud? 

Mr. LOVELAND. Absolutely. 

Dr. BURGESS. Do you believe that a company has to have absolute proof of fraud before it reports a fraud to the Food and Drug 

Administration? 

Mr. LOVELAND. I don’t. But again let’s draw the distinction between what the FDA wants and what we are talking about here. 

The FDA wants reliable data. And whether it is sloppy or fraudulent, that is not reliable. So fraud would be to the far end perhaps 

of unreliable data, but we don’t want sloppy data either. 

Dr. BURGESS. Right. So at that point, regardless of whether it 

is—whether you believe it to be fraudulent or just simply sloppy, 

what then is your obligation to report to the Food and Drug Administration? 

Mr. LOVELAND. Well, I couldn’t find an absolute written statutory 

obligation, but common sense says when you have this many indiVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00026 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
23 

cators, if you can’t figure it out yourself, pick up the phone and call 

FDA. The doctors and the scientists that I interviewed at Aventis, 

they knew DSI’s telephone number. They could have used it. 

Dr. BURGESS. So the level of concern should have been to notify 

the FDA. 

But you told Mr. Walden that you did not recommend that the 

FDA prosecute Aventis for fraud? 

Mr. LOVELAND. I can’t because I know that at the end of the day 

reasonable doubt exists, and I can’t get that past a jury. 

Dr. BURGESS. Do you think Aventis actually knew of this going 

on at these sites? 

Mr. LOVELAND. They should have. If they didn’t—— 

Dr. BURGESS. Knew it was sloppy or knew that it was intentionally fraudulent? 

Mr. LOVELAND. Either one. 

Dr. BURGESS. Either one. 

Mr. LOVELAND. Well, they knew it was sloppy. They used ‘‘sloppy’’ as an excuse not to throw the fraud flag. 

Dr. BURGESS. What prevented Aventis from acknowledging either 

sloppy or fraudulent? What caused them to stop short of saying 

this was a problem for us, too? 

Mr. LOVELAND. The study director said that unless they had reasonable proof of fraud, the data were going to get submitted. 

Dr. BURGESS. Thank you, Mr. Chairman. I will yield back. 

Mr. STUPAK. We will be going another round, so we will continue 

questions. 

Mr. Loveland, on page 5 of your report it indicates that you inspected five sites; is that correct? 

Mr. LOVELAND. Sir, OCI does not do inspections. 

Mr. STUPAK. It is on Exhibit No. 10 in the exhibit book there. 

Ms. Cisneros, if you could give it to him. 

We have your report there. And it looks like 19 or 11 sites you 

looked at. 

Mr. LOVELAND. I am sorry, the tab was 10? 

Mr. STUPAK. Yes, page 5 of your report. That is your report 

there, right, on page 10? 

Mr. LOVELAND. That is correct, sir. These are actually paragraphs—I did not—for the record, I didn’t go to any of these sites. 

Mr. STUPAK. OK. 

Mr. LOVELAND. These were actually removed from Aventis’ own 

files. 

Mr. STUPAK. So this page 5, these sites—Dr. Sarkar, Dr. Barber, 

Dr. Franklin, Dr. Sghiatti, Dr. Garner, Dr. Monticciolo, Dr. Jeffrey 

McCloud, Dr. Stone, Dr. Lang, Dr. Terpstra, and Dr. Ann KirkmanCampbell—all that information about these sites then and the 

problems at these sites actually came from Aventis? 

Mr. LOVELAND. That’s correct. They had this knowledge. We 

didn’t have it. 

Mr. STUPAK. Right. And you included this in your report? 

Mr. LOVELAND. Yes. 

Mr. STUPAK. And in each one of these they are alleging problems 

and protocol violations which were significant enough to affect the 

integrity of the Study 3014? 

Mr. LOVELAND. Data in it, yes, sir. 

24 

Mr. STUPAK. So Aventis definitely knew about—at least from 10 

sites that there were significant problems. 

Mr. LOVELAND. In actual fact, during one of the interviews, the 

interviewee told me that Aventis had 18 clinical investigators with 

whom they had significant GCP problems. 

Mr. STUPAK. Associated with the Study 3014? 

Mr. LOVELAND. That’s correct. That is a 1 percent ratio. But 

some of these here are the highest enrolling sites. 

Mr. STUPAK. So it is not just necessarily the number of sites, but 

also the number of patients enrolled at each site to make up your 

study, correct? 

Mr. LOVELAND. That’s correct. 

Mr. STUPAK. And this is significant then, even this 1 percent of 

the sites? 

Mr. LOVELAND. It was. And the reason I put it in the report is 

because it was—it explained the context of the data that were coming into the FDA from Aventis. 

It wasn’t just Kirkman-Campbell. The data were not reliable in 

other locations. 

Mr. STUPAK. Did you reach the conclusion then that the data relied upon or the data relied on in 3014 was unreliable? 

Mr. LOVELAND. I didn’t have to. DSI did that. They get paid to 

make that decision, and I do not disagree with it. 

Mr. STUPAK. OK. DSI? 

Mr. LOVELAND. Division of Scientific Investigation is a division 

within the Center for Drug Evaluation and Research, and they actually schedule inspections. They actually read the reports and 

issue the instructions and all those sorts of things. 

Mr. STUPAK. Very good. 

Agent West, if I may, you opened a criminal investigation shortly 

after the FDA clinical site investigator, Ms. Smith, investigated 

Kirkman-Campbell’s site; is that correct? 

Mr. WEST. That’s correct, sir. 

Mr. STUPAK. And that was in October of 2002? 

Mr. WEST. Yes, sir. 

Mr. STUPAK. What did Kirkman-Campbell do when you notified 

her that you were conducting this criminal investigation? 

Mr. WEST. When I approached Dr. Campbell at her clinic and 

asked to speak with her, the first thing that came out of her mouth 

was I will not speak with you unless I speak with Aventis personnel first. 

Mr. STUPAK. Do you know if she spoke with Aventis? 

Mr. WEST. I have no idea. But I’m assuming after I left she had 

to speak with Aventis because they had to prepare the 483. 

Mr. STUPAK. And that’s a—— 

Mr. WEST. That’s the response to the inspection. 

Mr. STUPAK. OK. So Kirkman-Campbell had to file this report in 

response to your inspection? 

Mr. WEST. It’s a response to the regulatory inspection, not my 

criminal case. 

Mr. STUPAK. Why were you convinced Aventis should be criminally investigated for knowledge of Study 3014? 

Mr. WEST. My feeling at the time was based on what I was observing, not only in Kirkman-Campbell’s clinical trial, but also my 

25 

interviews of PPD personnel, along with Aventis personnel. And I 

felt at the time that it was sort of like blatant disregard for information that they were receiving from the field and providing to the 

FDA. 

Mr. STUPAK. Do you still feel that today? 

Mr. WEST. Yes, sir. 

Mr. STUPAK. I understand that Dr. Kirkman-Campbell was the 

drug company sales representative to supply blood for the Ketek 

study, is that correct? 

Mr. WEST. That’s correct. 

Mr. STUPAK. Should the drug company representatives have 

known what the blood was being used for? 

Mr. WEST. Oh, I think they knew that Kirkman-Campbell was 

conducting a clinical trial. What they told me was that they were 

just going to allow her to use their name in a clinical trial so that 

they could continue to have her business as a pharmaceutical rep. 

Mr. STUPAK. By ‘‘they,’’ you mean the blood company representatives or Aventis? 

Mr. WEST. The company that each one of the pharmaceutical 

reps were representing at the time. 

Mr. STUPAK. In the course of your investigation, did Dr. 

Kirkman-Campbell, did you learn that Aventis had flown her to 

California to teach, so she could teach other people how to do these 

clinical trials? 

Mr. WEST. Based on what she told us is that, yes, Aventis flew 

her out to California so she could teach other PIs how to conduct 

clinical trials. 

Mr. STUPAK. PI being principal investigators? 

Mr. WEST. Principal investigators. 

Mr. STUPAK. To your knowledge, did Kirkman-Campbell do another study with Aventis? 

Mr. WEST. I think when I was there conducting my criminal 

case, not only was she conducting studies for Aventis, but she was 

conducting studies for GSK GlaxoSmithKline. 

Mr. STUPAK. Would you please take a look at the exhibit book, 

Exhibit Number 25, if you would. Could you identify what that exhibit is? 

Mr. WEST. This looks like an e-mail from Dr. Campbell to a 

member of Aventis basically saying thanks for assisting me in preparing the 483. 

Mr. STUPAK. And that is thanking Aventis for helping her fill out 

forms for another study, is that correct? 

Mr. WEST. That is correct. 

Mr. STUPAK. And that e-mail is dated November 17, 2002, is that 

correct? 

Mr. WEST. That is correct. 

Mr. STUPAK. Were you doing your criminal investigation of Dr. 

Kirkman-Campbell on Ketek at that time? 

Mr. WEST. Yes. 

Mr. STUPAK. Turn to Exhibit Number 8 if you would, please. 

Mr. WEST. Did you say 8? 

Mr. STUPAK. Eight, yes. In this memo, you’re recommending that 

the investigation should be undertaken by the FDA into whether 

26 

Aventis knew that Study 3014 contained fraudulent data when it 

was submitted to the FDA. Is that what that is about? 

Mr. WEST. That is correct. 

Mr. STUPAK. And who are you doing this study to in the FDA? 

Or, I’m sorry, your recommendation? 

Mr. WEST. In this particular e-mail, I was responding to Director 

Vermillion, who is the director of OCI. But the e-mail is in response to a conversation I had with CDER personnel, Dr. Solif, Dr. 

Goldberger, Dr. Cox and Dr.—well, this particular e-mail was just 

with those three individuals. 

Mr. STUPAK. When you say CDER, that’s Center for Drug Evaluation and Research, right? 

Mr. WEST. That’s correct. 

Mr. STUPAK. And you were trying to get them to allow you to 

continue the investigation into Aventis whether or not Aventis 

knew the fraud before they submitted 3014 to the FDA, correct? 

Mr. WEST. That’s correct. 

Mr. STUPAK. And what happened as the result of your conversations with officials at CDER? 

Mr. WEST. Well, first of all I have to say that the reason why 

I needed CDER support is that I don’t have the authority to go out 

and conduct inspections on PIs. I needed DSI to issue assignments 

to the regulatory so they could go out and do inspections. That’s 

what I was recommending to Goldberger, Solif and Cox. And I did 

not hear anything, I did not get a response from them. But I heard 

through the grapevine that they declined to participate because of 

personnel problems and money. 

Mr. STUPAK. Would it be a huge financial commitment of resources or money to do this investigation? 

Mr. WEST. No, because I was only asking for their support. In 

other words, provide assignments to regulatory to go out and actually conduct the inspections. OCI and other regulatory inspectors 

would have actually conducted the review of documents. 

Mr. STUPAK. And in this Exhibit Number 8, you basically lay out 

how you would do it, correct? 

Mr. WEST. That’s correct. 

Mr. STUPAK. How you would go about it. If you had this opportunity, you would go out and do this investigation and you were 

willing to go do it? 

Mr. WEST. That’s correct. 

Mr. STUPAK. Did you believe there was a possibility of detecting 

fraud if they just followed your recommendations as you laid out 

in Exhibit Number 8? 

Mr. WEST. Oh, I believe that we would have detected fraud in 

other sites. 

Mr. STUPAK. In your opinion, did someone at CDER, the Center 

for Drug Evaluation and Research at the FDA or elsewhere in the 

FDA block your proposal to create this task force to go look to 

criminally investigate Aventis in connection with Study 3014? 

Mr. WEST. I believe someone above the individual that I was 

speaking to, which was Brenda Friend, blocked the participation of 

the center to support OCI. 

Mr. STUPAK. Do you have any idea who that individual would 

have been? 

27 

Mr. WEST. I have no idea. 

Mr. STUPAK. Is it possible that because of the failure to investigate, Aventis personnel and others may have committed criminal 

violations of the Food and Drug and Cosmetic Act without being 

charged? 

Mr. WEST. Oh, most definitely. 

Mr. STUPAK. Did you ever talk to the Dr. Kweder from the FDA? 

Mr. WEST. Yes, I spoke with Dr. Kweder. I briefed her the same 

way I briefed Goldberger, Solif and Cox. I also provided her with 

the same recommendations. And I also explained to every one of 

them that we couldn’t, as OCI we couldn’t demand, because there 

was legal issues. If we demand them to do something and they go 

out and do it, then we’re sort of conducting a search which would 

have created a legal issue for us. So we recommended or suggested 

that they go out and do further inspections, which they declined. 

Mr. STUPAK. So besides Exhibit Number 8, this e-mail, you had 

other conversations with Dr. Kweder, Cox and others about where 

this investigation should go, in your recommendation it should continue to look at what Aventis knew prior to submitting this data 

to the FDA in Study 3014? 

Mr. WEST. Oh, yes. Not only those individuals, but I was in constant contact with DSI explaining to them what was going on in 

the criminal case so they could be aware because of 3014 being 

submitted and up for approval. 

Mr. STUPAK. Thank you. Mr. Ekey, we haven’t asked you any 

questions. Do you have anything you would like to add? 

Mr. EKEY. I’ll wait until you have a question. Thank you. 

Mr. STUPAK. OK. Mr. Walden. 

Mr. WALDEN. Thank you very much, Mr. Chairman. Mr. West, I 

want to follow up this notion about Dr. Campbell. You obviously 

found problems with her work in the Aventis case. I’m hearing for 

the first time she was involved in other trials, which I guess 

shouldn’t be a surprise. Has anybody gone back to look at her work 

in those other cases? 

Mr. WEST. We did. 

Mr. WALDEN. And did you find any instances of—— 

Mr. WEST. She was conducting a study for GSK. I can’t remember the drug. But it was for migraines. 

Mr. WALDEN. OK. 

Mr. WEST. And I think it was a post market study. And we determined just by reviewing three or four records, which were provided 

to us by GSK, that they were fraud. And we provided that information to GSK and to DSI. We were not going to incorporate that in 

the criminal prosecution because we had enough on her regarding 

3014, the Ketek study. But I made sure that both GSK and DSI 

were aware that we had proven that she committed fraud in the 

migraine study because she enrolled the same pharmaceutical reps 

in the migraine study. And we talked to them and they said, well, 

I didn’t have the symptoms, I was just participating because she 

asked me to. 

Mr. WALDEN. That was the phase 4 four-person Lantis study? 

Mr. WEST. I’m not quite sure. All I remember was the migraine. 

Mr. WALDEN. Do you know how big a study that was? The one 

we’re dealing with here with Aventis was what 12,000, 24,000 peoVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00031 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
28 

ple, 12 on a placebo, 12 not, and that was extraordinarily large. Do 

you know on the GSK study on migraine medicine? 

Mr. WEST. I believe that was a relatively small study. 

Mr. WALDEN. What would that be? Give me a number. 

Mr. WEST. I know for a fact that Campbell only had I think 12 

or 15 enrollees. 

Mr. WALDEN. Ms. Cisneros, do you know anything about that 

one? 

Ms. CISNEROS. I do. Actually, when I was at Dr. Campbell’s site, 

she had me make 50 copies of an informed consent for the GSK 

study. I had a colleague that worked at GSK in the neuro division 

that I made aware of the study. And to my knowledge, the study 

manager from GSK, as well as it was actually a PPD study as well, 

went out and auditing Campbell’s site and didn’t find any issues. 

Mr. WALDEN. Didn’t find any issues? But Mr. West, you said you 

found obvious fraudulent issues. Do you want to pull that mike 

back over your direction. What’s going on here? 

Mr. WEST. Well, I can tell you that Investigator Patty Smith and 

myself, we both reviewed records that were provided to us by GSK, 

and it was quite obvious that Campbell was committing fraud on 

that particular study. 

Mr. WALDEN. Do you know if GSK excluded her data from that? 

Mr. WEST. I have no idea. I provided the information to GSK and 

to DSI. 

Mr. WALDEN. Has that drug been approved, whatever it was? 

Mr. WEST. Well, it was already approved for one indication. I 

think this was a post market for an off label use? 

Mr. WALDEN. Do you know if that process has made its way 

through the system? Does anybody know? 

Mr. WEST. No. 

Mr. WALDEN. It just obviously troubles me that we seem to have 

the same doctor engaged in the similar sort of conduct allegedly involving yet another drug. And Ms. Cisneros, you indicate you were 

aware of this and made somebody else aware of this? 

Ms. CISNEROS. I did. 

Mr. WALDEN. And they disagree? 

Ms. CISNEROS. Well, they didn’t have to report back to me, so I 

don’t know what the outcome was. 

Mr. WALDEN. Who did you make aware of this? 

Ms. CISNEROS. I would rather not say her name, but a colleague 

that worked at GSK in that division that was marketing that drug. 

Mr. WALDEN. Well, Mr. Chairman, we may want to find out who 

that person was. 

Ms. CISNEROS. OK. Off the record. 

Mr. STUPAK. Ms. Cisneros has been forthcoming in all matters. 

If she wishes to tell us privately, since we don’t have an active investigation, maybe we should because we’ve uncovered some other 

stuff in working on this that there may be further investigations. 

So we’ll get that information. 

Mr. WALDEN. Thank you, Mr. Chairman. 

Mr. STUPAK. We certainly plan on following it up. 

Mr. WALDEN. Mr. Loveland, why do you believe it took almost 5 

years after the Study 3014 was submitted by Aventis for FDA to 

29 

open an investigation of the company and its knowledge of fraud? 

Why did it take 5 years? 

Mr. LOVELAND. Because for the first 3 years following Mr. West’s 

investigation throughout her indictment and her presentencing period all the way through her sentence, all the way through her appeals Kirkman-Campbell was convicted of defrauding Aventis. She 

never came forward and said Aventis knew also until the night of 

March 2, 2006. She had contacted Mr. West some time earlier that 

week or within a week or so. Mr. West went to the prison, interviewed her and sent an e-mail the following morning to my unit. 

The head of my unit at that time was Kathy Martin-Weis. And 

within an hour, that had been forwarded to Mr. Ekey and the case 

was undertaken. 

Mr. WALDEN. So nothing started from your perspective until Dr. 

Campbell? 

Mr. LOVELAND. We didn’t have a complaint that Aventis knew 

about it. 

Mr. WALDEN. So there wasn’t an effort not to investigate? 

Mr. LOVELAND. Right. 

Mr. WALDEN. You had no reason to investigate? 

Mr. LOVELAND. It never came to our office as a complaint. 

Mr. WALDEN. I see. Do you think it should have? Was there anything, Mr. West, that you found in the course of prosecuting or 

doing the investigation of Dr. Campbell that should have triggered 

somebody to look at Aventis? 

Mr. WEST. Well, we tried to get the support from the center. But 

in 2004, the drug was approved and we were involved with the 

Campbell prosecution. 

Mr. WALDEN. How many of these sorts of investigations do you 

undertake at a given time? What kind of caseload are we talking 

about here? 

Mr. WEST. Do you mean clinical trial investigations or all total? 

Mr. WALDEN. Give me a total. 

Mr. WEST. I probably am working right now on 15 criminal 

cases. And OCI cases are not ‘‘wham bam thank you ma’am.’’ They 

go on for 2 or 3 years, sometimes 4 years, sometimes 5. And they’re 

very paper intense, so. 

Mr. WALDEN. All right. Mr. Ekey, how about you? 

Mr. EKEY. Yes, sir. 

Mr. WALDEN. The number of cases you’re working on right now? 

Mr. EKEY. The group I was assigned to was the special prosecution staff which handled allegations on larger pharmaceuticals, so 

our caseload was lighter. We carried perhaps six, seven cases. 

Mr. WALDEN. All right. Mr. Loveland. 

Mr. LOVELAND. I currently have six cases, two or three of which 

are clinical trials. 

Mr. WALDEN. What kind of fraud training do you think pharmaceutical companies should provide to their employees? Do you think 

it’s adequate? What should it be? How do we prevent this from 

happening again? What do we need to do? 

Mr. LOVELAND. It wasn’t adequate in this case. I know of other 

companies that have very robust training programs and they manage to keep their clinical trials fairly fraud free. 

30 

Mr. WALDEN. But as we look at the number of sites, I think, 

what, were there 1,800 sites in this 3014 study? And each doctor 

got paid, what, $100 for every person they signed up? 

Mr. LOVELAND. $400 for each randomization. And that’s a very 

low number typically. 

Mr. WALDEN. Really? 

Mr. LOVELAND. Very, very small. 

Mr. WALDEN. So it’s sort of like getting somebody’s debit card and every time you sign somebody up you get another $400 withdrawal? 

Mr. LOVELAND. Interestingly, in this case, that’s part of what 

made this fraud work. Aventis uses the IVRS system to do basic 

data collection and drug randomization in many of its trials. It’s a 

great system. It’s a very good tool for capturing study data. What 

most people don’t know is that when you hang up the phone, it also 

sends a message over to accounting in finance and says send this 

doctor another $400 because they just randomized another patient. 

So what Kirkman-Campbell was doing, actually every 50 to 70 seconds, was printing a new $400 bill, and it would get mailed to 

her at the end of every month. Think about an ATM machine, and 

that’s how the system works. The system is actually constructed to 

have fraud indicators built in. And those fraud indicators were tripping. And PPD picked them up and PPD provided them to Aventis. 

And this is one of the two analyses that the mathematician did, not 

knowing that what he was looking at was a fraud indicator log. 

Mr. WALDEN. He didn’t know that? 

Mr. LOVELAND. He didn’t know it. 

Mr. WALDEN. Where did he think it came from then? 

Mr. LOVELAND. Well, it’s an administrative printout. It looks 

much like a telephone bill. 

Mr. WALDEN. So what did he think, it was like the button stuck 

down? 

Mr. LOVELAND. No. What he decided it was is that this lady was 

very adept at using the IVRS system. 

Mr. WALDEN. I would say so. I was a journalism major, not a 

math major, but I can figure that one out. 

Mr. LOVELAND. OK. And the story he got was that this particular 

clinical investigator would see 10, 12 patients, agreed to enroll 

them and then on her time off or on her lunch hour or on her day 

that she was closed and doing office work she would sit and randomize them all. 

Well, if you take the protocol and you read the protocol, you 

know you can’t do that. And one of the things that troubled me 

with the decision-making process is when I asked the management 

about that. They said, well, that’s a plausible answer, it may not 

be a good practice of medicine, but it’s a plausible answer, which 

immediately begs the question: Do you want not such a good practice of medicine in your clinical trial? 

Mr. WALDEN. Right. And it seemed like from the one tab I was 

reading, I think the chairman referenced, I don’t remember the 

exact page number or tab, but the problem with Dr. Campbell 

wasn’t unique—I mean, it may have been unique in that she’s in 

jail and did fraudulent activity, but it seemed like there were a lot 

of discrepancies in multiple locations, is that correct? 

31 

Mr. LOVELAND. I believe I was told by one member of management that there were problems with virtually every informed consent form, because doctors don’t tend to do those in the course of— 

in the normal practice of medicine. 

Mr. WALDEN. Right. But they’re not in the normal practice of 

medicine if they’ve agreed to participate in a clinical trial, are 

they? 

Mr. LOVELAND. That was one of the conflicts that was set forth 

in this whole case. One of the conflicts in this case was a large simple safety study, to my understanding, is typically done post marketing, not to good clinical practice standards. Every Phase III trial 

has to meet good clinical practice standards or the perception is the 

FDA will not accept the trial. So here we took a methodology that’s 

typically used apparently in Phase IV, not to good clinical practices 

and we moved it into Phase III. Everybody has looked at that and 

said, OK, that’s probably the last time we’re going to do that, it 

just didn’t work. 

Mr. WALDEN. All right. Thank you. Thank you, Mr. Chairman, 

for your indulgence on the time too. 

Mr. STUPAK. Sure, Mr. Walden. Mr. West, you may or may not 

know this. You talked about the migraine study. You said you notified DSI. That’s the Department of Scientific—— 

Mr. WEST. The Division of Scientific Investigations. 

Mr. STUPAK. That’s within FDA? 

Mr. WEST. That’s correct. Within the Center for Drugs. 

Mr. STUPAK. Right. CDER, Center for Drug Evaluation and Research? 

Mr. WEST. That’s correct. 

Mr. STUPAK. So FDA and the people responsible for making sure 

that drugs are safe and the approval of drugs, they knew not only 

about Aventis, but also about this migraine study that you mention? 

Mr. WEST. That’s correct. 

Mr. STUPAK. And I had asked you about Exhibit Number 25, 

which is actually where she faked Aventis, that’s my understanding actually, a diet pill. So those are at least three different. 

Do we know of any other studies that during this time frame 2002– 

2003 Dr. Kirkman-Campbell was involved with? We know of at 

least three. Do we know of any others? 

Mr. WEST. No, sir. 

Mr. STUPAK. Ms. Cisneros, do you know? 

Ms. CISNEROS. No. 

Mr. STUPAK. Mr. Ekey do you know of any other studies of Dr. 

Kirkman-Campbell? Or Mr. Loveland? 

Mr. EKEY. No, sir. 

Mr. LOVELAND. No, sir. 

Mr. STUPAK. Mr. Loveland, in your belated interview with the 

committee last Friday, you summarized your findings regarding 

Aventis’ complicity in Study 3014 clinical fraud as follows, and I’m 

quoting now, ‘‘Aventis should have known of the fraud. And if they 

really were unsure they should have contacted the FDA for assistance in substantiating the fraud.’’ Is that true? 

Mr. LOVELAND. Yes. 

32 

Mr. STUPAK. In a timeframe, 2002–2003, what would Aventis 

have known or what red flags were they aware of to make you 

make that statement? 

Mr. LOVELAND. During the period of time that the trial was enrolling, they probably did not know very much. There was one monitoring trip very early and they showed some small sloppiness 

things that could adequately be dealt with memos to file and some 

training. There was one auditing trip that was a catastrophe. The 

poor auditor, it was his first trip, he just joined the company, he 

walked in the door and expecting 100 or so patients found 360. He 

spent literally the entire 2 days going over informed consents. He 

never got to data in any meaningful fashion. 

Mr. STUPAK. And this auditor was an Aventis employee? 

Mr. LOVELAND. That’s correct. 

Mr. STUPAK. In what timeframe was that? 

Mr. LOVELAND. That was mid-January of 2002. 

Mr. STUPAK. OK. 

Mr. LOVELAND. In fact, it was January 22nd. He exited the place 

feeling uncomfortable and he reported to the study team, I’m not 

terribly comfortable with this site. 

Mr. STUPAK. The study team being the Aventis study team? 

Mr. LOVELAND. That’s correct. We need to increase the monitoring, we need to increase the source data verification, and we 

need to take a look at maybe some more training. But the trial was 

moving along so quickly that enrollment ended by January 30th so 

new people came in—or stopped coming in just a few days later. 

Mr. STUPAK. So even at the beginning of this study Aventis had 

red flags or warnings that things weren’t even starting off on the 

right foot? 

Mr. LOVELAND. I read that monitoring report. That did not look 

like a huge red flag. The first really serious sets of red flags started 

coming up with Ms. Cisneros’ visit. And during my investigation, 

I made it a point to go back and visit with her again and collect 

what is typically known as a smoking gun document, that document which she forwarded to Aventis, because that imputed more 

knowledge to Aventis than any other document in the case. 

Mr. STUPAK. That document, you mean the record of her phone 

call that we had cited earlier in this hearing? 

Mr. LOVELAND. She actually typed up a memo. Perhaps it was. 

Mr. STUPAK. OK. It would be Exhibit Number 4, I think we 

talked about. 

Ms. CISNEROS. I believe he’s talking about the forged document. 

Mr. LOVELAND. No. Your list of all the patients. 

Mr. STUPAK. Exhibit Number 4, I think we talked about. So that 

was the smoking gun that Aventis should have known and went 

there then? 

Mr. LOVELAND. That was the document, the teleconference. 

Mr. STUPAK. And that was in 2002? 

Mr. LOVELAND. That’s correct. 

Mr. STUPAK. And Ketek was approved in 2004. So two years before it was even approved Aventis knew? 

Mr. LOVELAND. Oh, sure. But this is even before Aventis submitted the data. So contemporaneously with the March 4th telephone conversation, some other folks at PPD sent some data up to 

33 

Aventis saying there’s some problems here as well. And then on the 

6th of March some more data came up saying there’s problems 

with these new forms. 

Mr. STUPAK. And this is all 2002. 

Mr. LOVELAND. That’s correct. So the period of time my investigation focused upon was from that period through the 23rd of 

July, because it was the 23rd of July that they submitted the data 

to the FDA. So during that period of time were they capable of 

learning that the data had been falsified? Well, employing the decision-making process that they did, they contend they never discovered the falsity of it. 

Mr. STUPAK. So there’s no doubt in your mind that Aventis knew 

before they submitted 3014 that there were major problems with 

the integrity of the data to support their conclusions that Ketek 

was safe based on Study 3014? 

Mr. LOVELAND. I’ll accept that wording. They contend they didn’t 

know it was fraudulent. But I’ll accept what you said. 

Mr. STUPAK. But there’s no way they would not know unless they 

just turned a blind eye to everything? 

Mr. LOVELAND. If you take a mathematical analysis and you take 

the first allegation and you say the first allegation is disproven, 

you take a mathematical analysis and you take that second allegation and the mathematical analysis disproves it, OK, that one is 

not true, I’m now down to sloppy and a forgery. We can fix sloppy 

with the memos to file and if the forgery falls off the radar I’m describing a fairly incompetent system here. 

Mr. STUPAK. Sure. Mr. West—excuse me one minute. I just want 

to go back to Agent Loveland. I want to ask you one more question. 

Tab number 14, if you take a moment, please, sir. Tab 14 is two 

pages. It looks like an e-mail you’re receiving dated Wednesday, 

April 14, 2007, and then Tuesday, April 17, 2007. 

Mr. LOVELAND. Where would you like me to go, sir? 

Mr. STUPAK. The second page, last paragraph. Could you explain 

that? I think this is from you to Ian Walsh. In Ketek new drug application, the sponsor clearly sent falsified data on Study 3014? 

Mr. LOVELAND. Right. 

Mr. STUPAK. Explain that for us. Aventis knew that such significant issues existed. It had so many sites that the GCP—what is 

that, GCP, what does that mean? 

Mr. LOVELAND. Good clinical practices. It’s a standard, sir. 

Mr. STUPAK. Right. Could not be claimed, yet it claimed a study 

was conducted to good clinical practice, GCP. Think—now, these 

are your words, right? 

Mr. LOVELAND. That’s correct. 

Mr. STUPAK. Think, ‘‘willful blindness,’’ on steroids, but they submitted anyway. What do you mean by willful blindness on steroids? 

Mr. LOVELAND. I had never seen, except in a trial conducted out 

of Florida, that was intentionally falsified, we put them in prison, 

I had never seen such a significant number of GCP issues. You referenced it earlier in the questioning, sir, when you took me to page 

4 of my first RRI, there’s 11 different sites that they themselves 

wrote up. And during the interview——— 

Mr. STUPAK. ‘‘They themselves,’’ you mean Aventis wrote up? 

34 

Mr. LOVELAND. That’s correct. And then in the interview, one of 

the managers said we had 18 folks with significant GCP issues. If 

you had 18 sites with significant GCP issues, why did you submit 

their data? 

Mr. STUPAK. Correct. I guess that will be for the Aventis panel. 

Let me ask you this, Mr. West. Since it appears you dealt with the 

FDA—wait for these buzzers. Let me ask you this. Since you dealt 

with the FDA, CDER, Center for Drug Evaluation and Research, 

and also the DSI, Division of Scientific Investigations, within the 

FDA, before Ketek was approved in 2004, is there any doubt in 

your mind that they knew there was fraud with Study 3014? By 

they, I mean the FDA officials. 

Mr. WEST. Oh, I had conversations with Brenda Friend many 

times. And she agreed with my recommendation that we needed to 

move forward because of the fact that it appeared that 3014 was 

just riddled with fraud. 

Mr. STUPAK. And she kicked it upstairs to CDER? 

Mr. WEST. She must have kicked it up to somebody, because she 

just—I think she works the ground level of DSI, so she had to kick 

my recommendation above her, and the people above her must 

have declined. 

Mr. STUPAK. Let me ask you this. In your opinion, has the statute of limitations run on the possibility of indicting Aventis for 

fraud in connection with Study 3014? 

Mr. LOVELAND. If I may, sir, that would be my case. 

Mr. STUPAK. OK. 

Mr. LOVELAND. And the answer is yes the statute of limitations 

has run with 3014. They submitted the data on July 23, 2002. It’s 

got five years. If I could find a law that went farther, I would use 

it. If I could have found a strict liability statute, I would have 

pushed for that. But I only had 1001, it’s 6 on the guidelines, it’s 

all I can do, that’s run, I can’t go back to it. 

Mr. STUPAK. OK. If Ketek is used for one of the, being used for 

three different; bronchitis, sinusitis and pneumonia, now it’s only 

supposed to be used for community-based pneumonia, if after July 

of 2002, it’s prescribed for bronchitis, contrary to what it’s supposed 

to be now, would that reinvigorate the statute of limitations? 

Would the statute of limitations start to run from the time it’s prescribed since its approval was based on 3014? 

Mr. LOVELAND. I’m not a lawyer and I’m not going to go there, 

but I don’t believe so. The only thing that I’m aware of that would 

allow us to take the statute beyond would be a subsequent affirmative step in the commission of a conspiracy. And we use that to 

lengthen the statute of limitations. I didn’t have that here. 

Mr. STUPAK. OK. If it was submitted in ’04, if Study 3014 was 

submitted—— 

Mr. LOVELAND. My statute of limitations would run next year. 

Mr. STUPAK. Right. So if they submitted the study, Aventis submitted the Study to the FDA, Study 3014, in 2004 for approval of 

this drug, the safety indicators, would not your 5 years run from 

’04 then? 

Mr. LOVELAND. ’04 to ’09, correct. 

Mr. STUPAK. So you still have a statute of limitations opportunity 

then for the possibility of indicting Aventis for fraud in connection 

35 

with Study 3014 knowingly submitting a fraudulent study to the 

FDA? 

Mr. LOVELAND. 3014 was submitted to the FDA in July of ’02, 

sir. 

Mr. STUPAK. Right. But it wasn’t approved until ’04, was it not? 

Mr. LOVELAND. I don’t know that that—I’m not—I can’t go there. 

I don’t know what that ties. 

Mr. STUPAK. Sure. OK. Mr. Ekey, I don’t want to leave you out, 

and I said I would ask you one. 

Mr. EKEY. Thank you, sir. 

Mr. STUPAK. I want to read you a short segment. And I don’t 

want to leave you out because the work all four of you have done 

and the willingness to come forward and testify, even though it was 

under subpoena, has been a great help to this committee, in the institutional review boards and CROs, all the things we’re looking at, 

so we certainly do appreciate all you’ve done and we take great 

stock in what you say. 

So let me just ask you this, because I just want to ask the statement that you read in your report. A short segment from the last 

page of your report. It’s Exhibit Number 9 in the book, if you care 

to look at it. The reporting special agent, that would be you, believes that the testimony and documentary evidence indicate that 

Aventis was well aware of serious data integrity problems at the 

Kirkman-Campbell site, yet submitted this data to the FDA. When 

questioned by the FDA review committee Aventis stated they had 

knowledge of problems but did not explain why this data wasn’t excluded from their submission, nor did they explain why they didn’t 

notify the FDA. Additionally, Aventis falsely claimed to have 

stopped enrollment at the Kirkman-Campbell site. So is it fair to 

say, based on that statement, that you came to believe that Aventis 

was aware of serious data irregularities when they submitted the 

data to the FDA? 

Mr. EKEY. I believe so, sir. I believe documents and interviews 

show that key Aventis personnel did know that there was serious 

integrity problems at that site. 

Mr. STUPAK. You also indicate the last line, ‘‘Aventis falsely 

claimed to have stopped enrollment at the Kirkman-Campbell site.’’ 

Explain that last paragraph. So even after they knew it, they continued to have Dr. Kirkman enroll patients? 

Mr. EKEY. Just for a little back story, I did leave the FDA in January of ’07, so I’m doing a lot of this without the benefit of notes, 

documents like that. My recollection is that is information I obtained from FDA doctors that were on that committee. That’s the 

best of my recollection. I don’t have that document. 

Mr. STUPAK. Doctors on that committee? 

Mr. EKEY. I believe it was Dr. Ross. 

Mr. STUPAK. OK. Would that be the advisory committee to the 

FDA that received the information? 

Mr. EKEY. Yes. 

Mr. STUPAK. Thank you. I have no further questions. And again, 

thanks to this panel. Mr. Inslee, thanks for getting here. I know 

at the early start, flights and all that, thanks for being here. Do 

you have any questions? 

36 

Mr. INSLEE. I do. Thank you. Just for the whole panel, I’ve been 

looking at this issue of fraudulent medical devices, alleged medical 

devices, that are used to take advantage of people who are in distress. And a local newspaper in Seattle has done some really good 

work looking at how many of these devices are now marketed to 

people who are in desperate situations. A lot of these electrical devices that have screens and sparks and everything else, but no 

medical validity. And one of the ways that folks have been able to 

do this is by using these independent review boards to sort of purport to be in some trial when they’re really just scams of the darkest dimension. 

I just want to ask you if you have any thoughts about these institutional review boards and how they are working or should work 

or may or may not be able to use to really cover up things that are 

not medically appropriate? Just looking for your advice. That’s an 

open question to any of you. Looking for free advice. 

Mr. LOVELAND. Sir, this really is not OCI’s bailiwick. 

Mr. INSLEE. I hear you. We’ll take advice from anywhere in 

America, though. We’re sort of an open review concept. Well, with 

that I’m going to thank you for your testimony. Thanks, Mr. Chairman. 

Mr. WALDEN. [Presiding.] You’re welcome, Mr. Inslee, and it’s 

great to be back in the Chair, if only by accident and for a very 

short period. I just have one question, Mr. Loveland, because you 

talked about statute of limitations and all that. It seems to me that 

there’s a disconnect in the FDA statutes. Are you familiar with the 

331q for medical device prosecution? 

Mr. LOVELAND. Yes. 

Mr. WALDEN. So if it was a medical device issue you could still 

pursue that under a different standard, correct, than drug issues? 

You could file a false statement and prosecute under a misdemeanor statute? 

Mr. LOVELAND. Well, 21 U.S.C. 331(q)(2) makes it a prohibited 

act to make a materially false statement to the FDA in any matter—in a required report in a matter involving a medical device. 

Mr. WALDEN. Right. 

Mr. LOVELAND. There is no similar statute for a drug, a food, a 

biologic or anything to regulate. 

Mr. WALDEN. Why is that? 

Mr. LOVELAND. I don’t know, sir. I thought laws come from you 

folks, not from us. 

Mr. WALDEN. The good ones do. Obviously, I’m feeling a new one 

coming on. 

Mr. LOVELAND. Let’s not make any new laws, just erase the last 

few words. 

Mr. WALDEN. Well, that takes a law to do that. 

Mr. LOVELAND. Instead of making it medical devices only, let’s 

make it a prohibited act to make a false statement to the FDA in 

any required report. Now, the beauty of the FDNC Act is that at 

the misdemeanor level it’s a strict liability statute. And in a case 

like this what the prosecutor and I discussed was sending a message to industry and what is the best way to do this. We can’t prosecute because the facts just aren’t there that will support a criminal prosecution at 18 U.S.C. 1001, which is the typical false stateVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00040 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
37 

ment statute. When we discussed that had, in fact, 331(q)(2) not 

been limited to medical devices, I would very much have been advocating to send a strict liability misdemeanor. And misdemeanors 

are not fun to prosecute. They take up a lot of time and they’re 

typically thought to—— 

Mr. WALDEN. But it does give you a hammer. 

Mr. LOVELAND. But it would have sent a message to industry 

that you are responsible for your data, all of them. You have to protect your clinical trials and you have to protect the sanctity of your 

data. It just wasn’t available to us. 

Mr. WALDEN. It would seem to me if it is good enough for a medical device, it should especially be good enough as another tool for 

you to use for the safety of our food and drugs. 

Mr. LOVELAND. I would have liked to have it that day, sir. 

Mr. WALDEN. All right. Thank you. I don’t think we have any 

other witnesses. I’ll let the chairman make that decision, though. 

Mr. STUPAK [presiding]. Again, let me thank this panel and 

thank you very much for being here and thank you for your work. 

We’ll call our third panel. Senator Grassley is still delayed. He will 

be here. We do plan on hearing from Senator Grassley today. He 

has just asked for our indulgence. And we’ll certainly accommodate 

the Senator. 

We will call our next panel. Dr. Paul Herbert Chew, President 

of U.S. Research and Development Division at Sanofi-aventis Pharmaceuticals; Dr. Fred Eshelman, Chief Executive Officer at PPD; 

and Ms. Sharon Hill Price, Chief Executive Officer and Chairman 

of the Board at the Copernicus Group IRB. It is the policy of this 

Subcommittee to take all testimony under oath. Please be advised 

you have the right within the Rules of the House to be advised by 

counsel during your testimony. Do any of our witnesses wish to be 

represented by counsel? Dr. Chew, would you please state the 

name of your counsel. 

Dr. CHEW. Mr. Chairman, the counsel for the company is Mr. 

Daniel Kracov from Arnold and Porter. 

Mr. STUPAK. OK. Dr. Eshelman. 

Mr. ESHELMAN. Counsel is present. Mr. Robert Nicholas from 

McDermott Will. 

Mr. STUPAK. And Ms. Price. 

Ms. PRICE. My counsel are Ann Begley and Gary Yingling from 

K&L Gates here in D.C. 

Mr. STUPAK. OK. I’m going to ask you to please rise, raise your 

right hand and take the oath. 

[Witnesses sworn.] 

Mr. STUPAK. Please let the record reflect that all witnesses replied in the affirmative. Each and every one of you are under oath. 

We will take an opening statement for 5 minutes. You may submit 

a longer statement for the record if you wish. 

Mr. STUPAK. From our left, we’ll start with you Dr. Chew. If you 

would start please, sir, for an opening statement. 

38 

STATEMENT OF DR. PAUL HERBERT CHEW, PRESIDENT, U.S. 

RESEARCH AND DEVELOPMENT DIVISION, SANOFI-AVENTIS 

PHARMACEUTICALS 

Dr. CHEW. Thank you. Chairman Stupak, Congressman Walden 

and Members of the Subcommittee, I’m Dr. Paul Chew, President 

of Research and Development for Sanofi-aventis U.S. Sanofi-aventis 

is a global research-based company dedicated to improving human 

health and addressing unmet medical needs. Patient safety is our 

highest priority. I’m here today to provide the Sanofi-aventis perspective on the issues raised regarding our antibiotic Ketek, and in 

particular, the conduct of Study 3014. I’ll focus first on the issues 

that arose in Study 3014 and then on what we learned from this 

experience. While I was not directly involved in the design or conduct of Study 3014, I’ve carefully reviewed the matter. Let me 

begin by stating that we fully acknowledge that Aventis made several incorrect assumptions about achieving compliance in Study 

3014. 

We greatly regret that Dr. Kirkman-Campbell’s fraud and certain 

problems at other sites were not identified or confirmed during the 

study. And we respect FDA’s actions regarding Study 3014. We 

strongly believe however, that Aventis submitted the Study 3014 

report in good faith believing that the good clinical practice issues 

that had been addressed—that had been addressed under the 

preestablished monitoring plan and that the integrity of the safety 

data had not been effected. Study 3014 was the first large 

preapproval anti-infective drug study conducted in a usual care setting. 

The purpose of this supplemental study, which was conducted 

after the completion of the pivotal studies for the drug, was to further assess adverse events of special interest seen in the earlier 

pivotal studies, but in the real world physician’s office setting and 

patient population. Study 3014 was never intended to find every 

possible adverse effect event that could occur in the future Ketek 

population. No single study can accomplish that goal. In conducting 

the study Aventis at its contract clinical research organization, 

PPD identified and addressed a range of deviations from good clinical practice. At the highest enrolling site, that of Dr. KirkmanCampbell, numerous GCP violations were identified during the 

trial and questions were raised at that time regarding the legitimacy of certain practices and data. 

Those questions were actively investigated by Aventis and PPD 

under a documented investigation plan. And Aventis and PPD required Dr. Kirkman-Campbell to act upon their findings. As you 

know, however, FDA subsequently documented investigative fraud 

at that site and Dr. Kirkman-Campbell pled guilty to falsifying 

clinical records. Aventis cooperated fully in that initial investigation and Sanofi-aventis has cooperated fully on all subsequent investigations. While numerous GCP violations were identified, it’s 

our belief that Aventis was unable to confirm actual fraud at the 

Kirkman-Campbell site. It’s important to know that FDA criminal 

investigators have tools at their disposal that are typically unavailable to study sponsors and monitors. So what have we done to address what we know now about Study 3014? 

39 

Since 2004, when Sanofi acquired Aventis to sponsor the Study, 

we’ve undertaken a comprehensive review of our policies, procedures and training. Let me share a few of these lessons learned. 

First, it’s important to improve our ability to address investigator 

fraud. Sanofi-aventis has enhanced its approach to investigating 

potential fraud and persistent GCP noncompliance. We have also 

mandated additional training in these areas for all personnel engaged in study activities. This experience has also reinforced the 

importance of transparency in our interactions with FDA. In retrospect, Aventis could have been more proactive in bringing the 

issues encountered at high enrolling sites, and particularly the 

Kirkman-Campbell site, to the attention of the agency. 

In addition, more real-time on-site monitoring may have mitigated many of the issues in Study 3014. Thus we’ve revised our approach to site initiation and monitoring to ensure that study sites 

are visited shortly after the first subjects are enrolled to help ensure protocol adherence and to detect potential problems. Sanofiaventis has also implemented systems and procedures to strengthen the evaluation, the selection and training of investigators. 

Finally, many of the problems in Study 3014 occurred at high enrolling sites. We recognize that strict controls of site enrollment are 

essential in every study. Our current procedures incorporate new 

provisions limiting the number of patients enrolled and the rate of 

enrollment. 

In closing Mr. Chairman, we recognize the serious nature of the 

problems identified in Study 3014. However, I urge you to separate 

out what we know now about Dr. Kirkman-Campbell and other 

sites from what Aventis was able to determine at the time as the 

study sponsor. We have provided FDA with detailed information on 

the comprehensive steps that we’ve taken. The FDA, Congress and 

the American public have the unequivocal commitment to Sanofiaventis to rigorous and compliant clinical research. 

On behalf of Sanofi-aventis, thank you for the opportunity to participate in today’s hearing. We understand your interest in these 

important issues and I look forward to answering your questions. 

I ask that my statement be included in the record of today’s hearing. Thank you. 

[The prepared statement of Dr. Chew, M.D. follows:] 

40 


48587.043
41 


48587.044
42 


48587.045
43 


48587.046
44 


48587.047
45 


48587.048
46 


48587.049
47 


48587.050
48 


48587.051
49 


48587.052
50 


48587.053
51 


48587.054
52 


48587.055
53 

Mr. STUPAK. Your statement is included in the record, as all 

statements are. Dr. Eshelman, do you have an opening statement 

please, sir? 

STATEMENT OF DR. FRED ESHELMAN, CHIEF EXECUTIVE 

OFFICER, PPD. INC. 

Mr. ESHELMAN. Yes, sir, I do have a statement. Good morning, 

Chairman Stupak, Congressman Walden and members of the subcommittee. I’m Fred Eshelman, founder and CEO of Pharmaceutical Product Development, also known as PPD. It is my pleasure to be here today as a representative of PPD. At this time, I also 

ask that my written statement be made part of the record. PPD is 

a global contract research organization or CRO. We provide drug 

development services to pharmaceutical, biotechnology and medical 

device companies and also government organizations, all of which 

are referred to as sponsors. As a CRO, PPD is hired by sponsors 

of clinical trials to perform obligations of the sponsors arising 

under the Federal Food Drug and Cosmetic Act and FDA’s clinical 

study related regulations. Principally, 21 C.F.R. Parts 50, 56, 312 

and 812. Under FDA regulations a sponsor may transfer the legal 

obligations for compliance with regulatory requirements to a CRO. 

FDA regulations require that any delegation of authority be set 

forth in a written agreement. 

Under FDA regulations any obligation that is not specifically 

transferred to the CRO is retained by the sponsor. These requirements are set forth in 21 C.F.R. Section 312.52. In the fall of 2001, 

PPD contracted with Aventis to perform specific services in connection with the study of Ketek Study 3014. These obligations are set 

forth in detail in my written testimony. Other than these enumerated obligations Aventis did not contract with PPD to perform additional services. With regard to addressing investigative misconduct 

Federal regulations require that the sponsor either secure compliance or end the investigator’s participation in the study. If an investigator is terminated then the FDA must be notified. This requirement is set forth in 21 C.F.R. Section 312.56(b). 

Under our contract with Aventis, PPD was to report any investigator that did not comply with the study plan to Aventis. We did 

not, however, have the authority to end an investigator’s participation in the study or to report an investigator’s conduct to the FDA. 

During Study 3014, PPD staff uncovered compliance concerns at 

the site of an investigator now familiar to this subcommittee, Dr. 

Anne Kirkman-Campbell. PPD’s monitoring team made its first 

visit to the Kirkman-Campbell site in late November of 2001. In 

February of 2002 PPD’s monitoring team visited the KirkmanCampbell site for a second time. During the visit, PPD personnel 

determined that the site failed to document critical source information. 

PPD staff also found many inconsistencies and modifications regarding patient signatures on informed consent forms. Further, 

subjects appeared to have been randomized to the study in extremely high volumes during short time intervals. Additionally, 

PPD monitors found staff at the Kirkman-Campbell site to be uncooperative. 

54 

At the same time with the February visit, PPD also analyzed 

data from the Kirkman-Campbell site regarding patient blood samples due to concerns raised by our staff. Based upon PPD’s review, 

there appeared to be a lack of variability among blood samples 

shared by many patients. The data suggested that the KirkmanCampbell site engaged in blood sample splitting, which is assigning 

a patient’s blood sample to one or more patients in order to maximize enrollment totals. In light of these concerns, PPD staff asked 

for a conference call with Aventis. 

On the March 4, 2002 call, PPD personnel set forth in detail 

their concerns about the Kirkman-Campbell site. At the conclusion 

of that call, Aventis said that it would look into Kirkman-Campbell’s compliance issues and devised an action plan. First, Aventis 

said that it would initiate its own analysis of the Kirkman-Campbell lab data to determine the probability that the site had engaged 

in blood sample splitting. Ultimately, Aventis informed PPD that 

it had analyzed the lab data and that the data was not indicative 

of scientific misconduct. Second, the Aventis study manager was 

tasked with contacting Dr. Kirkman-Campbell about the site’s informed consent and randomization problems raised by PPD. Ultimately, Aventis and PPD sent a follow-up letter to Dr. KirkmanCampbell raising these issues. Mr. Chairman, on behalf of PPD, I 

would like to thank you for the opportunity to testify before this 

subcommittee. I hope that my testimony provides the subcommittee 

with a better understanding of PPD, the regulatory and contractual 

framework that governs our conduct and our role in the KirkmanCampbell matter. I would welcome any questions that you have. 

Thank you. 

[The prepared statement of Mr. Eshelman follows:] 

55 


48587.056
56 


48587.057
57 


48587.058
58 


48587.059
59 


48587.060
60 


48587.061
61 


48587.062
62 


48587.063
63 

Mr. STUPAK. Ms. Price, for your opening statement, please. 

STATEMENT OF SHARON HILL PRICE, CHIEF EXECUTIVE OFFICER AND CHAIRMAN OF THE BOARD OF DIRECTORS, COPERNICUS GROUP IRB. 

Ms. PRICE. Thank you. 

Mr. STUPAK. Press that button there. 

Ms. PRICE. I found it now. OK. 

Mr. STUPAK. Thanks. 

Ms. PRICE. Good morning. My name is Sharon Hill Price, and I 

am the chief executive officer of Copernicus Group Institutional Review Board. I would like to thank the committee for providing me 

an opportunity to make a statement today. 

An IRB’s regulatory mandate is to assure the protection of the 

rights and welfare of human subjects in clinical trials. In our current system, the IRB’s responsibility to protect subjects is shared 

with the investigators, the institutional sponsor, and the government. An IRB carries out its unique role by reviewing study information provided by sponsors and investigators and determining 

whether the research adheres to the ethical principles of the Belmont Report and Federal regulations. As CEO, my responsibilities 

are to direct the administrative functions at Copernicus, while the 

separate ethical review function is conducted and controlled by our 

independent Institutional Review Board. 

On a personal note, I built this company from the ground up, and 

have always strived to assure that Copernicus provides the highest 

quality ethical review. We are deeply troubled with what has happened in 3014, and I, along with the dedicated employees at my 

site, certainly are interested in the findings of this committee. 

In August 2001, Copernicus was contacted by PPD and asked to 

serve as IRB of record for Study 3014, a clinical trial sponsored by 

Aventis. This was a large, multicenter trial, as you know, conducted over a relatively short duration of approximately 6 months. 

Copernicus initially reviewed and approved the protocol as well 

as the consent document that was be to used by each investigator 

as they worked in the process with their subjects. Additionally, the 

IRB reviewed information for each of the investigators selected by 

the sponsor and provided oversight for any information that was 

provided by the investigator throughout the study. 

One of those investigators was Dr. Kirkman-Campbell. Dr. 

Kirkman-Campbell’s submission packet was reviewed around October 2001, and she was granted IRB approval to serve as a Study 

3014 investigator. 

At a committee hearing last year, Ann Marie Cisneros, a former 

PPD employee, testified that during a monitoring visit to the 

Kirkman-Campbell site in February of 2002, she had called Copernicus and spoken to the President and informed her of concerns 

found at the site. Her statement surprised us at Copernicus, because no one on the staff at that time was aware of any such call 

having been made. And I, as President, did not recall any such call. 

Furthermore, at the time, our searches of documents did not turn 

up any evidence of a call from Ms. Cisneros. 

However, on the afternoon of Wednesday, January 23rd, 2008, in 

preparation for a meeting with the committee staff, Copernicus did 

64 

find documentation of an anonymous call being taken by one of our 

professionals on February 24th, 2002—excuse me, February 21st, 

2002. Based upon its content, this memo appears to describe a call 

from Ms. Cisneros, and it was, I think, briefly mentioned earlier 

this morning. For some reason, and contrary to both procedure and 

training, this memo was not forwarded to a supervisor by the employee or to the Institutional Review Board, as it should have been 

at the time. Neither was the document placed in the investigator 

file as it should have been. 

We have intensely investigated this matter, but we simply do not 

have an answer for why this lapse occurred. Had the Board received the information, as it should have at the time, I am confident that the Board, the IRB, would have investigated the matter 

and taken appropriate action. While I cannot speak specifically to 

the independent decision the Board would have made, the action 

most likely would have included notifying the FDA about concerns 

of the investigator. This call should have been elevated to the 

Board. It was not. And on behalf of my company, I offer an apology 

for this deviation from our standard operating procedure. 

In a recent interview in the Journal of Clinical Research Best 

Practices, Ms. Cisneros encouraged individuals to reach out to 

someone if they have concerns about research study conduct. I 

wholeheartedly agree with this advice. There are a number of options open to individuals faced with similar concerns, and the IRB 

should certainly be one of those options. The IRB is a place where 

both subjects and members of the research community can turn 

when issues about how a clinical trial is being conducted arise or 

if unanticipated problems that affect subject safety are suspected. 

As additional regulatory guidance has been released over the 

years, Copernicus has continually reviewed and strengthened its 

policies and procedures in the past 6 years since Study 3014 ended. 

The IRB and professional support staff have been trained on existing policies, including those that govern the handling of unanticipated problems such as the kind that arose in Study 3014. Our ongoing process improvement efforts continue to strengthen our ability to recognize and appropriately address serious issues that rise 

to the level of unanticipated problems that pose risks to subjects 

or others. 

Of additional significance, I think, to the committee is that Copernicus was one of the first groups to achieve a voluntary accreditation of our human subject protection program, this done by the 

Association for the Accreditation of Human Research Protection 

Programs, or AAHRPP, that is based right here in D.C. In order 

to attain this voluntary accreditation, Copernicus went through a 

rigorous self-assessment of our policies and practices and peer-review process to determine or to demonstrate that strict practice 

standards had met or exceeded the Federal human subject protection Requirements. Copernicus was recently reaccredited this past 

October. 

In closing, I would like to say that Copernicus takes its role as 

a human subject protection entity very seriously, and has done so 

for the past 12 years since opening our doors in 1996. Although we 

sincerely apologize for the call that was not handled as it should 

have been 6 years ago, we remain proud of the important and inteVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00068 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
65 

gral role that IRBs plays in providing ethical review into clinical 

research. 

Again, I appreciate the opportunity to testify today, although a 

little nervous, and I am prepared to answer any questions you 

might have. Thank you. 

Mr. STUPAK. Thank you. 

[The prepared statement of Ms. Price follows:] 

STATEMENT OF SHARON HILL PRICE

Good morning. My name is Sharon Hill Price and I am the Chief Executive Officer 

of Copernicus Group Institutional Review Board. I would like to thank the Committee for providing me an opportunity to make a statement and testify today. 

An IRB’s regulatory mandate is to assure the protection of the rights and welfare 

of human subjects in clinical trials. In our current system, the IRB’s responsibility 

to protect subjects is shared with the investigators, the institution or sponsor, and 

the government. An IRB carries out its unique role by reviewing study information 

provided by the sponsor and its agents, and by investigators engaged to perform the 

study, and determining whether the research adheres to the ethical principles outlined in the Belmont Report as set forth in federal regulations. As CEO, my responsibilities are to direct the administrative functions at Copernicus, while the separate 

ethical review function is conducted and controlled by our independent Institutional 

Review Board. On a personal note, I built this company from the ground up, and 

I take what happened in Study 3014 very seriously. I have always strived to assure 

that Copernicus provides high quality ethical review. 

In August 2001, Copernicus was contacted by PPD and asked to serve as IRB of 

record for Study 3014, a clinical trial sponsored by Aventis Pharmaceutical, now 

known as the Sanofi-Aventis Group. This was a large, multi-center trial conducted 

over a relatively short duration of approximately 6 months. Copernicus initially reviewed and approved the protocol as well as the consent document that was to be 

used by investigators during the informed consent process with study subjects. Additionally, the IRB reviewed information for each of the investigators selected by the 

sponsor. One of those investigators was Dr. Kirkman-Campbell. Dr. Kirkman-Campbell’s submission packet was reviewed and in October 2001 she was granted IRB 

approval to serve as a Study 3014 investigator. 

At a committee hearing last year, Ann Marie Cisneros, a former PPD employee, 

testified that during a monitoring visit to the Kirkman-Campbell site in February 

2002, she had called Copernicus and spoken to the President and informed her of 

concerns found at the site. Her statement surprised us at Copernicus because no 

one on our staff was aware of any such call having been received. Furthermore, at 

the time, our searches of documents did not turn up any evidence of a call from Ms. 

Cisneros. 

However, on the afternoon of Wednesday, January 23, 2008, Copernicus found 

documentation of an anonymous call being taken by one of our professionals on February 21, 2002. Based upon its content, this memorandum appears to describe the 

call from Ms. Cisneros. For some reason, and contrary to both procedure and training, this memorandum was not forwarded to a supervisor or to the Institutional Review Board as it should have been at the time. Neither was the document placed 

in the investigator file as it should have been. We have intensively investigated this 

matter, but we simply do not have an answer as to why this lapse occurred. Had 

the Board received the information, as it should have, I am confident that the Board 

would have investigated the matter and taken the appropriate action. While I cannot speak to the independent decision that would have been made by the Board, 

this action most likely would have included notifying the FDA regarding concerns 

about the investigator. This call should have been elevated to the Board. On behalf 

of my company, I offer an apology for this deviation from our standard operating 

procedure. 

In a recent interview in the Journal of Clinical Research Best Practices, Ms. 

Cisneros encouraged individuals to reach out to someone if they have concerns about 

research study conduct. I wholeheartedly agree with this advice. There are a number of options open to individuals faced with similar concerns and the IRB should 

certainly be one of those options. The IRB is a place where both subjects and members of the research community can turn when issues about how a clinical study 

is being conducted arise or if unanticipated problems that affect subject safety are 

suspected. 

66 

As additional regulatory guidance has been released, Copernicus has continually 

reviewed and strengthened its policies and procedures in the six years since Study 

3014 has ended. The IRB and professional support staff have been trained on existing policies, including those that govern the handling of unanticipated problems 

such as the kind that arose in Study 3014 in 2002. Our ongoing process improvement efforts continue to strengthen our ability to recognize and appropriately address serious issues that rise to the level of unanticipated risk to subjects or others. 

As part of that effort at strengthening our procedures, and of additional significance, Copernicus was one of the first groups to achieve accreditation of our human 

research protection program by the Association for the Accreditation of Human Research Protection Programs (AAHRPP). In order to attain this voluntary accreditation, Copernicus went through a rigorous self-assessment and peer review process 

to demonstrate strict practice standards that meet or exceed federal human subject 

protection requirements. Copernicus was reaccredited this past October. 

Copernicus has taken its role as a human subject protection entity seriously for 

the 12 years since first opening its doors in 1996. Although we sincerely apologize 

for the call that was not handled as it should have been six years ago, we remain 

proud of the important role that IRBs play in providing ethical review of clinical 

research. Again, I appreciate the opportunity to testify today and am prepared to 

answer any questions that you have. 

Mr. STUPAK. Mr. Walden for questions, please. 

Mr. WALDEN. I appreciate that, Mr. Chairman. Unfortunately, I 

have to leave for another meeting, so I appreciate your courtesy. 

Ms. Price, this issue of the call sheet that appeared that you 

found—— 

Ms. PRICE. Yes. 

Mr. WALDEN [continuing]. Obviously must be very troubling to 

you to have provided so many documents to various investigations 

and not had that among them in the past. Where did you find it? 

Ms. PRICE. We found that in an electronic file in a shared drive 

that was shared by different personnel at Copernicus. And it was 

not made part of the hard copy file, which is, unfortunately, what 

we tended to look at mostly during the course of this investigation. 

Mr. WALDEN. So you never looked at that drive before when you 

were producing documents? 

Ms. PRICE. No, we didn’t look particularly at that drive. We had 

done electronic searches on the drive and had come up with that 

document back in 2006 when Senator Grassley requested information about—— 

Mr. WALDEN. You had come up with that document? 

Ms. PRICE. We had—an electronic search had come up with that 

document at the time that Grassley requested information. However, Grassley’s investigation centered on information received 

2006 and after. 

Mr. WALDEN. OK. 

Ms. PRICE. And so that wasn’t looked at as part of that. 

Mr. WALDEN. OK. So you had—you knew you had that document. 

Ms. PRICE. It came up in a search. We hadn’t looked at it, you 

know. 

Mr. WALDEN. I see. And you said you had done a thorough investigation on all of this. Did you do a forensics investigation, then, 

on the computer drive just to make sure, you know, when it was 

done? 

Ms. PRICE. Yes, as part of that investigation was looking at the 

properties—I think that is what you are referring to, the properties 

of the document. And it was generated and only touched on one 

67 

day, and that was February 22nd, 2002, the day after it was supposedly—the call was supposedly made. 

Mr. WALDEN. I think the document actually says the 21st on it. 

Ms. PRICE. The document actually says the call was made on the 

21st. But the document, according to the properties, was generated 

on the 22nd. 

Mr. WALDEN. Thank you. That helps clear that up. 

Dr. Chew, I would like to ask you a couple of brief questions. Do 

you agree or disagree with the contention of an FDA criminal investigator that Aventis’s system for overseeing the clinical trials in 

the 3014 study was not designed to enable your company to detect 

criminal fraud? 

Dr. CHEW. Congressman Walden, there was a specific process in 

the former company looking for scientific fraud. And in the case of 

Dr. Kirkman-Campbell, the teleconference that was alluded to on 

March 4th, 2002—the minutes were March 6th, but the meeting 

clearly had as its title ‘‘The Discussion of Scientific Misconduct.’’ 

And it is my belief, looking back at those records, that the team, 

both Aventis and PPD, were following the process of trying to look 

at scientific fraud. And it was clear that the team—in fact, it was 

an Aventis employee that in January, 17th and 18th, had gone to 

the site and reviewed 327 informed consents. That was in January, 

and it was at that charge that PPD was asked to make the February visits—which Ms. Cisneros was there. 

So there was an early detection of a potential problem. And the 

monitoring responsibility was clearly delegated, and where we 

found out even more issues that needed to be addressed. And these 

are minuted in the scientific fraud discussion of March 4th. 

Mr. WALDEN. What would you do differently today than what 

was done then? Because it sounds like you are describing for me 

a system that worked. And yet we know it didn’t work. 

Dr. CHEW. Well, as I said, I was not involved in the trial. 

Mr. WALDEN. Right. 

Dr. CHEW. And looking back at the record, and with the benefit 

of hindsight I wished, for transparency, that the FDA had been 

called. As you heard this morning, there is really no clear guideline 

on when to call, short of scientific misconduct. I wish they had been 

called. I wish Aventis had picked up the phone and said, We have 

a problem. We can’t document it. 

What I saw, though, was an enormous amount of resources were 

spent at Dr. Kirkman-Campbell’s site, with over 165 phone calls. 

I think she had four monitoring visits. Probably more was expended trying to look at that. 

And the other problem, and you heard that this morning, is when 

you do a big trial, 24,000 patients, among physicians who are not 

used to doing that, frankly, this was the first trial of an antibiotic 

of that scale done preapproval. 

Mr. WALDEN. Why did Aventis take such efforts to bring her into 

compliance? 

Dr. CHEW. Why did Aventis? 

Mr. WALDEN. Yeah. 

Dr. CHEW. I think as a matter of course when you do monitoring, 

even though be it by the nature of the program it was retrospecVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00071 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
68 

tive, is to identify issues, to document issues, and that they were 

not overlooked. 

Mr. WALDEN. Now, we heard earlier that—from I think Mr. 

Loveland—that basically Aventis brought in mathematicians to do 

statistical analyses of data that were coming out of a system designed to identify potential fraud. The phone records, the fact that 

Dr. Campbell was dialing every 50 to 70 seconds. Can you speak 

to that? 

Dr. CHEW. From my review of the record, first of all I think it 

is—it was identified that there would be a statistical approach to 

look at the variations in blood samples. Because if there were split 

blood samples, they might tend to look more alike than normally 

would occur between people. So that there was an attempt by the 

statistician. Unfortunately, not enough baseline data was there for 

his preferred analysis. So what he did was to compare the variability of blood samples at Dr. Kirkman’s site with another site. And 

there was not conclusive data to show that this was a fraudulent 

blood sample. So that was the purpose of looking statistically at the 

blood samples. 

Mr. WALDEN. Well, do you believe that extensive violation of 

GCPs in a clinical trial can affect data integrity, even when there 

is not fraud? 

Dr. CHEW. Congressman, we believe that is possibly the case. In 

this particular case I am talking about Dr. Kirkman-Campbell. 

What we heard was that it was not so much a question of whether 

the patients existed, because from my review of the record she randomized 407 patients. I believe there was only one case—of course 

it is very serious—but I believe there was only one case in which 

there was a patient made up of whole cloth. 

Mr. WALDEN. But didn’t she have a lot of patients that didn’t fit 

the requirements for the trial? 

Dr. CHEW. The requirements of the trial, in a real-world setting 

of a real-office practice, was to look at patients who had acute exacerbations of chronic bronchitis, sinusitis, or walking pneumonia, 

community-acquired pneumonia. 

Mr. WALDEN. So all of her patients had that? 

Dr. CHEW. Well, she was asked—all investigators were asked to 

use their clinical diagnosis. It was not required, just like it isn’t in 

the real world, to require—— 

Mr. WALDEN. So you are not telling me that she diagnosed that 

all those people on her trial had walking pneumonia or one of the 

other two issues, right? 

Dr. CHEW. It is my understanding that she represented that 

these patients had the qualifying diagnoses. 

Mr. WALDEN. And you say there is only one patient that was 

made up. Do you think those data, out of the 400 patients, should 

have been used in this evaluative process? 

Dr. CHEW. Well, again looking back, I could see that the data 

was addressed, it was documented. I think the best efforts were 

made—I don’t think, I don’t think—— 

Mr. WALDEN. There were forgeries, though, weren’t there? 

Dr. CHEW. There was one alleged forgery. 

Mr. WALDEN. What was she convicted of, then? 

69 

Dr. CHEW. She was convicted of falsifying clinical records using 

interstate mail. 

Mr. WALDEN. And how many clinical records did she falsify? 

Dr. CHEW. I would have to review that. 

Mr. WALDEN. Only one? 

Dr. CHEW. No, she pled guilty, I believe, to one count, but there 

were many allegations. 

Mr. WALDEN. So you have reviewed all 400 records, and you still 

only believe there was one that was bad? 

Dr. CHEW. From my review of the criminal documents, there was 

one that was made up out of whole cloth. But there were serious 

problems with the other patients because—and this is very important—these patients were not properly consented. Many did not 

know they were participating in a clinical trial. Because the investigators were able to talk to patients. And from my review of the 

record, sponsors, and, in this case, Aventis, did not talk to patients 

and inquire about their status. 

Mr. WALDEN. Do you have to talk to patients to find fraud? 

Dr. CHEW. In this case I think the bulk of the issues were informed consent—the bulk of the issues were involving patients who 

were not aware. 

Mr. WALDEN. That they were in a clinical trial. 

Dr. CHEW. That they were in a clinical trial, that they were taking experimental medicine, the reasons their bloods were drawn. 

That is very serious. 

Mr. WALDEN. Do you think Aventis has any liability in a situation like that, since you are responsible for the trials and overseeing them? 

Dr. CHEW. Any pharmaceutical company, in particular in this 

case Aventis, has to submit, to the best of their knowledge, the 

highest quality data. I don’t want to make any ambiguity about 

that. And they need to submit that with all the due diligence possible. One of the lessons learned, again, was not only could Aventis 

in retrospect have called, but also they could have put in more documentation in the final study report of gray-area issues, even if 

fraud had not been actually documented. 

Mr. WALDEN. Can you assure the committee that your standard 

operating procedures today have changed sufficiently that this 

won’t be replicated? 

Dr. CHEW. I can assure you, Congressman Walden, that the procedures and the training—we have even brought in the former, I 

think, deputy head of DSI to talk with and train our people. We 

have now also made a very big change in the standard operating 

procedure. Not only is it scientific fraud, but it is serious noncompliance with the GCP that will raise the bar for detection and 

procedures throughout the company. 

Mr. WALDEN. And one final—well, did Dr. Kirkman-Campbell 

participate in any other Aventis trials? 

Dr. CHEW. Yes, she did. 

Mr. WALDEN. And have you reviewed that work? 

Dr. CHEW. Yes, I have. 

Mr. WALDEN. Have you found any problems with any of those 

data? 

70 

Dr. CHEW. To my knowledge this was an insulin trial, with four 

patients, that was started. She was recruited, to my knowledge, 

independently of the Ketek team. 

Mr. WALDEN. Right. 

Dr. CHEW. They were unaware at the time when they included 

her that there was a problem, but once this was found, when she 

requested additional patients, the answer was no. And she was 

shortly thereafter, I think—— 

Mr. WALDEN. Right. But of those she already had in the other 

trial, were there any problems with her data? 

Dr. CHEW. To my knowledge there were no issues. 

Mr. WALDEN. Have you reviewed her data? Do you have any 

knowledge—— 

Dr. CHEW. I have not been made aware of any issues. We could 

provide—— 

Mr. WALDEN. My question is, Have you reviewed those data? 

Dr. CHEW. I have only reviewed issues that have come up with 

her data. And that was not listed as one of the issues. 

Mr. WALDEN. All right. Have you or have you not looked at the 

data out of the other trial? 

Dr. CHEW. In the other trial, I have not looked at her four-patient data. 

Mr. WALDEN. All right. So of course you wouldn’t have any 

knowledge that there is a problem there, because you never looked 

at those data. 

Dr. CHEW. I believe—— 

Mr. WALDEN. That’s fair. I am just trying to get an answer. 

Dr. CHEW. No, I believe if there had been an issue in the records 

with Dr. Kirkman-Campbell, with any of her participation, I am 

confident I would have been made aware. 

Mr. WALDEN. So somebody else in your company has looked at 

those data? 

Dr. CHEW. I am confident they have, because this was approximately 2003 we are talking about. 

Mr. WALDEN. I will leave it up to the Chairman, but it would be 

interesting to know for sure. Thank you. 

Mr. STUPAK. Ms. Price, you said in response to Mr. Walden’s 

questions that Senator Grassley asked for some documentation 

there, and you found that memo but you didn’t turn it over to Senator Grassley’s committee? 

Ms. PRICE. No. Senator Grassley requested us to look at a lot of 

documents. And working with counsel, they determined that the information that they wanted was 2006 onward. 

Mr. STUPAK. So you became aware of this document at Senator 

Grassley’s request, right? And this document—— 

Ms. PRICE. This is on rereview of information. 

Mr. STUPAK. Document number 33, right there. Exhibit No. 33. 

Ms. PRICE. That’s the telephone contact report of February 21. 

Mr. STUPAK. At Senator Grassley’s request you came across this 

document, correct? 

Ms. PRICE. In review—in review and preparation for the meeting 

with your staff we became aware—— 

Mr. STUPAK. No, no. I am asking about Senator Grassley. In your 

testimony and questions with Mr. Walden, you said you came 

71 

across this document when Grassley—when Senator Grassley 

asked for it, but it was outside the purview of his request; therefore 

you did not give it to him. Correct? 

Ms. PRICE. It was not responsive to his request. 

Mr. STUPAK. When was that? That was about a year ago, wasn’t 

it? 

Ms. PRICE. That was 2006. That was a year before your hearing. 

Mr. STUPAK. 2006. So you have known about this document since 

2006, then, the existence of this document. 

Ms. PRICE. It appeared on a long listing of thousands of documents. 

Mr. STUPAK. Right. And you knew about it in 2006, correct? 

Ms. PRICE. That’s what our investigation turned up as we were 

looking into this. 

Mr. STUPAK. So then why did you sit on the document until the 

day before committee staff interviewed you, even though we had 

the request in for about a year? Why did you sit on it for a year 

until the day before the interview? 

Ms. PRICE. We didn’t sit on it. 

Mr. STUPAK. What did you do with it, then, for a year? 

Ms. PRICE. We were aware of it on an electronic search. 

Mr. STUPAK. In 2006 you are aware of it. 

Ms. PRICE. Yes, in 2006. We hadn’t opened the document in 2006 

to look at it because it wasn’t in response to what Senator Grassley—— 

Mr. STUPAK. Sure. So you looked at it and said, This doesn’t go 

for a Senator. 

Ms. PRICE. It appears that nobody looked at it. 

Mr. STUPAK. How would you know if it was in keeping with Senator Grassley’s request, then, if you didn’t look at it? 

Ms. PRICE. It showed up on an electronic data search. It showed 

up simply as a telephone contact report. It had a date of when it 

was written. 

Mr. STUPAK. Sure. What was the date it was written? 

Ms. PRICE. I would have to look back, but I think that the 

date—— 

Mr. STUPAK. And that electronic search would also have the person who entered the information on that document, would it not? 

Ms. PRICE. The electronic search did not have an author, I don’t 

believe, on it. 

Mr. STUPAK. You don’t know or you don’t remember? 

Ms. PRICE. I don’t remember—I don’t remember. 

Mr. STUPAK. Is that a computerized form right there, Exhibit No. 

33? Is that a computerized form? 

Ms. PRICE. Yes, it is. It is a Word document. 

Mr. STUPAK. So your backup files would have when it was entered and by whom, would it not? 

Ms. PRICE. Yes. That’s why it turned up on the electronic search. 

When we narrowed down our search criteria to—— 

Mr. STUPAK. Sure. So your electronic search would have who entered it, then, correct? 

Ms. PRICE. The electronic search that I remember seeing did not 

have who entered it, no. 

72 

Mr. STUPAK. So you have a document retention policy, do you, at 

your organization, at your company? 

Ms. PRICE. Yes, we do. 

Mr. STUPAK. OK. So can you provide us with that electronic 

search log which indicates this document was a part of it? 

Ms. PRICE. I would be happy to. 

Mr. STUPAK. OK. I am going to ask you this. The telephone document—I should say telephone contact—indicates that Sarah Wallace took the report, right? 

Ms. PRICE. Yes, sir. 

Mr. STUPAK. But the testimony has been that Ms. Cisneros 

talked to you. Correct? 

Ms. PRICE. That was her initial testimony. 

Mr. STUPAK. And that was her testimony this morning, too. 

Ms. PRICE. Today she said she thought she spoke to the President. 

Mr. STUPAK. Right. And she identified you as the President, 

right? 

Ms. PRICE. She did not identify me as the President until after 

you asked her who the President was. 

Mr. STUPAK. Right. So she identified you as the President. OK. 

And you are claiming you never talked to her. 

Ms. PRICE. That’s correct. I never talked to her. 

Mr. STUPAK. What is your company’s policy on filling out this 

form here, this telephone contact form? Is it supposed to be done 

when the contact was made, or do you do it the next day? What 

was your company policy on filling out this document? 

Ms. PRICE. At the time, the company policy was to fill out telephone contact reports for any significant issues. And obviously, 

Sarah Wallace felt this was significant enough to fill out a telephone contact. 

Mr. STUPAK. Right. Is there a time frame when she is supposed 

to fill out this contact? 

Ms. PRICE. There was no timeframe given in our—— 

Mr. STUPAK. So she could do it a week later if she felt compelled 

to do it a week later? 

Ms. PRICE. Yes, but she had been trained to do it soon after the 

call. 

Mr. STUPAK. Who trained her to do it soon after the call? 

Ms. PRICE. Training at that point was done by our Director of 

IRB Services and/or myself and other experienced professionals. 

Mr. STUPAK. OK. And Ms. Wallace left Copernicus shortly after 

this call was received. Is that correct? 

Ms. PRICE. Yes, she did. Within 2 weeks, I believe. 

Mr. STUPAK. And in an interview with Ms. Wallace, she stated 

to committee staff she did not remember getting this call, but she 

was certain that if she had gotten the call she would have immediately notified you or Dawn Pope because of the extraordinary 

content of the call. 

Do you think she would have contacted you if she would have received the call? 

Ms. PRICE. She must have told you all that, yes. And I feel that 

it is highly unusual to get a call like this, and she would have remembered to forward that on to her supervisor. 

73 

Mr. STUPAK. OK. So who had been her supervisor then? 

Ms. PRICE. Our Director of IRB services. 

Mr. STUPAK. Who is that? 

Ms. PRICE. Dawn Pope. 

Mr. STUPAK. OK. Did Dawn Pope ever talk to you about receiving 

this call or the information she received from Sarah Wallace? 

Ms. PRICE. No, sir. 

Mr. STUPAK. So what happens to this information when serious 

allegations like this are made? What would happen if you would 

have been informed? What would have happened? 

Ms. PRICE. This type of call should have been forwarded to a supervisor, and then would have eventually gotten to the Institutional Review Board, where it would have been investigated and 

action taken by the Board. 

Mr. STUPAK. So did you talk to Ms. Pope about whether or not 

she ever received this document? 

Ms. PRICE. Certainly, yes. 

Mr. STUPAK. And what is her response? 

Ms. PRICE. She does not remember this either. 

Mr. STUPAK. So Ms. Wallace just filled out this form and it sat 

in your files? 

Ms. PRICE. It appears so. It appears to be a human error, and 

I wish I could explain it, but I cannot. 

Mr. STUPAK. Well, who would—does it indicate who she forwarded that to, Ms. Wallace—does it indicate who Ms. Wallace forwarded it to? 

Ms. PRICE. No. 

Mr. STUPAK. Would your electronic file indicate who she forwarded it to? 

Ms. PRICE. Excuse me? 

Mr. STUPAK. Would your electronic files show who she would 

have forwarded it to? 

Ms. PRICE. I don’t know the answer to that. I would have to find 

out. But I think that we looked to see if it had ever been printed, 

because that was one of our concerns, too. This should have been 

not only generated, but also printed and put in the investigator 

hard-copy file. 

Mr. STUPAK. OK. So what happened? Did a hard copy go into the 

investigative file then? 

Ms. PRICE. No, it did not. And that was where the rub was. It 

should have gone into the file. 

Mr. STUPAK. So this serious allegation went to your organization 

and it just sat there. Never forwarded it, no hard copies ever made, 

nothing. 

Ms. PRICE. That’s correct. 

Mr. STUPAK. Would Ms. Wallace know to make a hard copy and 

put it in the file? 

Ms. PRICE. Would Ms. Wallace what? Excuse me? 

Mr. STUPAK. Ms. Wallace would have made a hard copy, right? 

Ms. PRICE. The person who took the call would have normally—— 

Mr. STUPAK. That’s what she should have done? 

Ms. PRICE. Yes, sir. 

74 

Mr. STUPAK. So—OK. Do you know how many protocol violations 

or deviation forms you received on Study 3014. 

Ms. PRICE. On the entire Study 3014? 

Mr. STUPAK. Yes. 

Ms. PRICE. No, but there were quite a few memos to file. 

Mr. STUPAK. What did you do with the information then? You 

had quite a few complaints about Study 3014. What did you do 

with the information? 

Ms. PRICE. Our policy at the time was to not review protocol violations. We were concentrating on serious adverse events that were 

reported by the investigators for the study. 

Mr. STUPAK. So you are saying your violations that you heard of 

were only protocol violations and not serious adverse events. Right? 

Ms. PRICE. That was our procedure at the time. We have now 

certainly changed that. 

Mr. STUPAK. So protocol violations, no matter the number, wasn’t 

alarming to your organization, to Copernicus? 

Ms. PRICE. Not at the time, no. We felt that those were things 

that were picked up on the monitoring visits and were corrected at 

the site—with the site at that time. 

Mr. STUPAK. How do you know if they were corrected? You said 

you assumed they were corrected. How do you know that? 

Ms. PRICE. In some cases it is an assumption, in some cases the 

actual memo to file did indicate that there was reeducation of the 

investigators. 

Mr. STUPAK. Turn to Exhibit 32, if you would, in the book there. 

This document is entitled procedure number 108. It reflects the 

procedures at Copernicus with respect to safety and noncompliance 

reporting requirements. Correct? 

Ms. PRICE. Yes, that’s correct. 

Mr. STUPAK. OK. Were you under duty to notify the IRB when 

you received protocol violations? Isn’t that what it says? 

Ms. PRICE. Under duty to inform the IRB of protocol violations? 

Mr. STUPAK. Sure. Sure. 

Ms. PRICE. Let me take a look here and see—do you know which 

number it’s addressed in? 

Mr. STUPAK. Number 6. 

Ms. PRICE. The Board is responsible for reporting investigator 

noncompliance as required by applicable Federal regulations. 

Mr. STUPAK. Sure. So were you required to notify the IRB when 

you received protocol violations? 

Ms. PRICE. Our interpretation of the regulations at that point did 

not constitute us reporting protocol violations to the Board. 

Mr. STUPAK. So now you believe you are required to do so? 

Ms. PRICE. We have evolved a lot in 6 years as an Institutional 

Review Board, as has the industry, and now require the investigators to report unanticipated problems. And that’s what this would 

have arisen to. 

Mr. STUPAK. So when did Copernicus start, then? When did your 

company start? When did you start? You said you founded the company. When did you do that? 

Ms. PRICE. 1996, sir. 

Mr. STUPAK. 1996. So you are in 6 years since when you started 

seeing the problems, then, with Kirkman-Campbell, right? 

75 

Kirkman-Campbell, 2002, when you were doing this work here for 

Aventis and all that, correct? 

Ms. PRICE. We became IRB of record, or were asked to be IRB 

of record in 2001. 

Mr. STUPAK. OK. But in 1996 you had been an IRB, right? 

Ms. PRICE. Yes, we started in 1996. 

Mr. STUPAK. So you had more than one IRB before 2001, right? 

Ms. PRICE. We had one—I don’t understand your question. 

Mr. STUPAK. OK. You said you were asked to be an IRB in 2001. 

Correct? 

Ms. PRICE. For 3014, yes, sir. 

Mr. STUPAK. But before that, you had been an IRB before, right? 

Since 1996 you had served as an IRB. 

Ms. PRICE. Yes. 

Mr. STUPAK. So you certainly knew the requirements. If you 

didn’t know the understanding of procedure number 8 or paragraph 

number 6 there, entitled Procedure Number 108 reflects procedures 

of Copernicus with respect to safety and noncompliance reporting 

requirement, why would you have it if you didn’t understand what 

it meant? It is your own procedures. 

Ms. PRICE. We did understand what it meant at the time. The 

interpretation was protocol violations did not constitute serious adverse events or unanticipated problems. The whole industry has 

evolved since then. And we feel that we have systems in place now 

and policies and procedures that would address this. 

Mr. STUPAK. So this one case, this Study 3014, has changed the 

whole industry standard on the way you do things? 

Ms. PRICE. No, sir. There has been an evolution going on for a 

long time, and I think the area of unanticipated problems is certainly one that we deal with constantly. As late as April 2007 there 

has been some draft guidance from FDA regarding what needs to 

be submitted to the IRB and what would constitute an unanticipated problem. 

Mr. STUPAK. How many memos to the file or protocol violations 

did you receive just regarding the Kirkman-Campbell site alone? 

Ms. PRICE. We received 83, I believe, 83 memos to file of protocol 

violations, and we received them 3 months after she closed as an 

investigator. 

Mr. STUPAK. So you received 83 different complaints. Given the 

number and nature of the informed consent and other violations, 

didn’t you have an obligation to ensure patient safety at these 

sites, or at least inquire from the sponsor to see what was taking 

place? 

Ms. PRICE. We had no authority after she was closed to do anything about it. And no, we did not report them to the FDA. 

Mr. STUPAK. OK. Well, I have got plenty more questions, but 

Senator Grassley is here. So I think we are going to suspend this 

panel for now. We will ask you to stay. 

Senator Grassley would like to testify. And we will accommodate 

the Senator. We are going to have him come up and testify. 

Mr. MARKEY. Mr. Chairman? 

Mr. STUPAK. Yes. 

Mr. MARKEY. May I be recognized? 

76 

Mr. STUPAK. No. We are going to do the courtesy to Senator 

Grassley. He is going to testify. 

Mr. MARKEY. Oh, I am sorry. 

Mr. STUPAK. And this panel will be back, so you will have a 

chance to ask questions. I didn’t mean to cut you short, but we 

want to get the Senator in. 

Mr. STUPAK. Senator, welcome. It is the policy of this committee 

to take all testimony under oath. I am sure you are not represented 

by counsel, sir? No? I will ask you to rise and take the oath. 

[Witness sworn.] 

Mr. STUPAK. Senator, you are now under oath. I would ask you 

to give your opening statement, please, sir. 

OPENING STATEMENT OF THE HON. CHARLES GRASSLEY, A 

UNITED STATES SENATOR FROM THE STATE OF IOWA 

Senator GRASSLEY. OK. I thank you very much for the invitation 

to come and testify. 

Mr. STUPAK. Senator, you want to turn your mike on? 

Senator GRASSLEY. It is not on. OK. Thank you. 

I thank you very much for the opportunity to be here. Thank you 

for your leadership in this area. Thank you for your investigation. 

I am going to limit my remarks to my work on what is called 

Study 3014. And that involves the safety of the drug Ketek. It has 

been a long road, and it still is not at an end. 

More than 2 years ago, in January 2006, the journal Annals of 

Internal Medicine reported three cases of liver damage in North 

Carolina patients who took Ketek. In response, the FDA issued a 

public health advisory. After all, suffering severe liver problems is 

quite a price to pay for taking an antibiotic that was being used 

for such conditions as sinus infections, until that indication was removed from the Ketek label a year ago. 

Soon after I heard allegations and concerns regarding the FDA’s 

review of Ketek, and I started asking questions. One of the more 

serious allegations was that the maker of Ketek, Aventis at the 

time, submitted clinical trial data to the FDA in support of approval, knowing it was fraudulent. 

So I asked FDA to make arrangements immediately for my staff 

to review documents related to Study 3014 at the FDA’s office. Initially, FDA gave my staff access and agreed to provide copies of 

documents my staff identified during their review. 

But then I asked for Special Agent Robert West from the FDA’s 

Office of Criminal Investigation, and the FDA then pulled a 180 on 

me. I had good reasons for asking for Agent West and being able 

to question him. One of the other allegations I received was that 

despite Agent West’s concerns and recommendations, FDA never 

expanded its investigation to determine if the company did, quoteunquote, knowingly submit fraudulent data. 

Agent West played an integral role in the investigation of Study 

3014, and I am delighted to see that he will be testifying before 

your committee today, if he hasn’t already. 

Agent West was the lead agent on the investigation of Dr. Ann 

Kirkman-Campbell, one of the principal clinical investigators for 

Study 3014. And as a result of that investigation, Dr. KirkmanCampbell is currently serving a 57-month prison sentence. 

77 

Agent West also was in frequent communication with FDA consumer safety officers and reviewers involved in Study 3014 inspections. But as I testified before this subcommittee a year ago, FDA 

and HHS wouldn’t make Agent West available, even after I went 

over to the HHS offices to ask personally to speak with Agent West 

and subpoenas were issued. After all, if FDA had nothing to hide 

about how it handled Study 3014, why stop me from talking to 

Agent West? 

Obviously, not being able to talk to him at that point, I smelled 

a cover-up; in fact, even before then. 

Well, I now have a better understanding of why FDA did not 

want me to speak to Agent West regarding Ketek. The answer to 

the ‘‘why’’ question is equally interesting. It seems to me that there 

were definitely reasons why the FDA did not want me to meet 

Agent West, or any other agents for that matter. FDA, it appeared, 

did not want anyone to know that it didn’t further investigate 

whether or not Aventis submitted fraudulent data knowingly to the 

FDA. The FDA did that even though Agent West recommended in 

the summer of 2003, almost 5 years ago now, to high-level officials 

at the FDA that it needed to create a mini-task force to look into 

Aventis. 

When HHS and FDA finally made Agent West available a short 

time ago, and that was 18 months after I first requested him, 

Agent West confirmed that no one acted on his recommendations. 

In fact, I learned from HHS more than a year after my visit to the 

Department that the FDA didn’t open an investigation into the 

company until March 2006. Interestingly, that was about the same 

time that I started poking around the Ketek issue itself. 

Agent West told his supervisors, FDA investigators involved in 

the Study 3014 inspections, as well as FDA directors overseeing 

the review of Ketek what he thought needed to be inspected; in 

other words, inspect all of the study sites that enrolled over 100 patients. The protocol for Study 3014 had recommended a maximum 

enrollment of 50 patients per site, so that that would have meant 

inspections of about 70 sites. 

Agent West’s supervisors told my staff that they supported him. 

The site investigators also thought that it was a good idea. 

So then what happened? The head of the Office of Criminal Investigations told my staff that Agent West’s concerns and recommendations were referred up the food chain, and he assumed 

the matter would be taken care of. The Associate Commissioner of 

Regulatory Affairs at that time said he was prepared to offer any 

assistance, if needed, but never heard anything more from the Office of Criminal Investigations. 

One of Agent West’s superiors said that the Center for Drug 

Evaluation and Research folks were briefed, so the ball was then 

in their corner. He also said that Agent West’s task force proposals 

had nothing to do with concerns about Aventis. 

But I have since learned that that was not true. Agent West sent 

an e-mail July 2003 to his superiors about his conversation with 

directors in the Federal FDA Center for Drug Evaluation and Research. These directors oversaw the review of Ketek. In that e-mail, 

Agent West said, quote, I told them that it was my opinion that 

78 

Aventis’s new sites were suspect, and did nothing to prove or refute 

their suspicions, end quote. 

Agent West was not the only agent who believed that the company, or at least someone within the company, knew that there 

were serious problems, particularly at Dr. Kirkman-Campbell’s 

site. 

You have the two agents here today who were assigned to the 

criminal investigation that was opened in March 2006, Special 

Agents Robert Ekey, and Douglas Loveland. Agent Ekey said, during a joint interview with our committees, that he thought the company too easily dismissed the concerns that were raised by his own 

contract research organization, the organization that was hired for 

the specific purpose of monitoring Study 3014. 

Agent Loveland wrote in an internal e-mail dated April 17th, 

2007 that the company knew significant issues existed at many 

sites, yet the company submitted the data to the FDA and claimed 

the study was conducted according to good clinical practices. He 

also told my staff during an interview yesterday that Aventis 

should have known there were problems with the integrity of the 

study data. 

The case was closed July 2007. FDA issued a warning letter in 

October to the company for failing to ensure proper monitoring of 

Study 3014 and not adequately investigating allegations of fraud at 

Dr. Kirkman-Campbell’s site. The letter cited many of the same 

problems that FDA staff raised back in 2003 and 2004. So why 

wasn’t the investigation initiated at that time? 

Agent West stated in his July 2003 e-mail, quote, I think the 

three individuals in CDER understood my feelings and opinions, 

but I don’t know whether or not the necessary steps will be accomplished, end quote. When my staff spoke with the three directors, 

one of them told my staff that if the Office of Criminal Investigation wanted additional investigations, it was their call, not CDER’s. 

He also said that the Office of Criminal Investigations should have 

talked to the Division of Scientific Investigations, since the division 

oversees clinical trial site inspections. 

So who was responsible? Everyone seemed to be pointing a finger 

at somebody else, with the exception of the head of the FDA’s Office of Division of Special Investigations. This FDA employee told 

my staff that as far as additional inspections went, they didn’t have 

the resources to do more. And besides, she said, one, the FDA 

didn’t rely on Study 3014 for approval. Two, FDA completed eight 

site inspections for Study 3014, which is many more than the one 

or two it normally does. And three, astonishingly, she also said 

that investigating drug companies is a, quote-unquote, losing game, 

and the chances of getting a warning letter seemed to be near zero. 

I find that attitude, as you should, extremely troubling. We rely 

on the FDA to ensure that the drugs in our medicine cabinets are 

safe and effective. That includes FDA making sure that the data 

supporting the safety and efficacy of the drug is sound. To do that 

adequately, FDA has to do its job of oversight over clinical trials. 

Data integrity isn’t the only issue of concern here. FDA also has 

an obligation to protect human subjects. In December I raised this 

matter with Commissioner von Eschenbach in a lengthy letter reVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00082 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
79 

garding my Ketek investigation. That letter, I have been told, is included in your exhibit books. 

I asked Commissioner von Eschenbach if it is FDA’s position that 

no additional inspections are required once a study is no longer 

useful for regulatory action. Then how can FDA protect research 

subjects from the harm that may be caused by clinical investigators? Not relying on a study for approval does not absolve FDA of 

its responsibility to protect the individuals who courageously volunteer in clinical trials so that we can all benefit from life-saving 

cures and medical innovations. I am still waiting for the Commissioner’s comments on this very important matter. 

Of course, this responsibility does not lie only with the FDA. Of 

course this responsibility goes beyond FDA. The drug companies 

also have a responsibility to the people who participate in their 

clinical trials. They also need to ensure that problems are adequately investigated and addressed. 

In the case of Study 3014, there were many sirens, red flags, 

bullhorns, but it looks like the company and the FDA kept ear 

plugs in and blinders on. 

I would like to close with this. There is something that strikes 

me as ironic about the case involving Ketek and another investigation involving Dr. Victoria Hampshire, an employee of the FDA. 

Today we heard a lot about the missteps made by FDA and 

Aventis. The culmination of these missteps led to a warning letter 

being sent to Aventis, as opposed to potentially more serious action 

being taken. 

And then we have the case of Dr. Hampshire, where the FDA 

worked mightily to pursue her. In fact, the FDA went so far as to 

send a criminal referral to the United States attorney in Maryland 

to prosecute her for alleged wrongdoing. Disturbingly, the FDA 

wrote a criminal referral that was riddled with inaccuracies about 

Victoria Hampshire. Perhaps in the future the FDA would pursue 

alleged bad behavior by corporations with the same vigor, same 

persistence and creativity, with which it pursued Victoria Hampshire. 

So, if there are no objections, I would request that my letter to 

Dr. von Eschenbach about the intensive investigation done by the 

FDA against one of its own, meaning Victoria Hampshire, be 

placed into the record. 

Mr. STUPAK. Without objection, it will be part of the record. 

[The information appears at the conclusion of the hearing.] 

Senator GRASSLEY. So I thank you for your invitation and your 

patience with my schedule today, because we had nine votes on the 

Senate floor that kept me from being here at the appropriate time. 

I would like to not take questions, if that is possible. 

Mr. STUPAK. That is possible. Would you take a question from 

Mr. Dingell? 

Senator GRASSLEY. I will take questions. 

Mr. STUPAK. Mr. Dingell, do you have a question for Senator 

Grassley? 

Senator GRASSLEY. When you say I learned all my oversight 

work from him, how could I ignore him? 

Mr. STUPAK. I agree. I agree. Go ahead. 

80 

Mr. DINGELL. You are very kind, Mr. Chairman. I was waiting 

to hear your questions. 

Mr. STUPAK. Senator Grassley is on a tight schedule, so I would 

defer to the full Chairman for any questions. 

Mr. DINGELL. Then let me first welcome Senator Grassley. It is 

wonderful to see my old friend back here. Welcome back to the 

House, where you started. And it is a pleasure to see you in this 

room again, where we have done great work together, you and I, 

and I am very proud of your labors. 

So I will give you questions that in view of your time constraint, 

I think most of these will be answerable ‘‘yes’’ or ‘‘no.’’ 

Senator, from your testimony today and that which you graciously provided this committee a year ago, I take it you believe 

FDA and the Department of HHS have been extraordinarily uncooperative in your inquiry into the matter. Is that correct? 

Senator GRASSLEY. The answer is yes, and I think Agent West 

is the best example of that. 

Mr. DINGELL. Now, I note that lack of cooperation, including 

defying one or more lawful subpoenas issued by you as Chairman 

of the Senate Finance Committee. Is that correct? 

Senator GRASSLEY. We have had difficulty getting those responses even with a subpoena. And again, Agent West is an example. 

Mr. DINGELL. That related both to appearances of personnel and 

also production of papers. Is that correct? 

Senator GRASSLEY. Very true. 

Mr. DINGELL. I take it that you still have serious questions as 

to exactly what the Department wished to avoid revealing to your 

committee. Do you agree that FDA has been forthcoming with the 

public regarding the safety of this drug Ketek? 

Senator GRASSLEY. Very definitely. 

Mr. DINGELL. So now, FDA, after acknowledging that the pivotal 

safety study for Ketek was full of clinical fraud, approved the drug 

anyway, claiming there were insufficient adverse events reported 

in countries such as Italy and Brazil to prove that it was not safe. 

Is that correct? 

Senator GRASSLEY. Well, that’s correct from the standpoint that 

I think that those are things that Agent West pointed out that 

needed to be further investigated. I am not sure that I can speak 

to the points about the other countries that you made mention of. 

But basically, I am referring now to my staff, and they said basically the answer is yes. 

Mr. DINGELL. And it doesn’t make sense to you, does it? 

Senator GRASSLEY. No, obviously not. I hope my testimony made 

very clear that I am incensed that, when we are doing our constitutional job of oversight, that we don’t get the cooperation from the 

executive branch of government. 

Mr. DINGELL. Now, I believe it is sort of the fact, the rule of 

thumb in the United States is that only about 10 percent of adverse events get reported. Is that right? 

Senator GRASSLEY. Approximately. Yes. 

Mr. DINGELL. Now, Senator, in fact, has FDA ever before or since 

made a safety determination for a new drug primarily on the basis 

81 

of the lack of adverse event data in the United States, much less 

in countries such as Brazil and Italy? 

Senator GRASSLEY. I think I will have to take a pass on that 

question. I am not sure I can answer that. 

Mr. DINGELL. It is my understanding that this is unprecedented. 

Senator GRASSLEY. OK. 

Mr. DINGELL. Would it be fair to say that the FDA officials that 

approved this drug discouraged information from their own investigators, and those were investigators trained both in the detection 

of scientific misconduct and criminal fraud, in an attempt to get 

the advisory committee reviewing the data from the fraudulent 

study to recommend approval? 

Senator GRASSLEY. The answer is yes, and that is a fair summary of some of the points I was trying to make. 

Mr. DINGELL. Now, Senator, did Aventis inform the advisory 

committee of data problems? Much less did they inform them of the 

existence of a fraud investigation when they presented the Study 

number 3014, the pivotal study in January 2003? 

Senator GRASSLEY. The answer is no. 

Mr. DINGELL. Do you believe that the field investigators, when 

they were allowed to do their jobs, worked diligently and competently to uncover wrongdoing at Aventis? 

Senator GRASSLEY. The answer is yes. And I refer specifically to 

Agent West that I worked so hard to get in contact with, but also 

others as well. But the others my staff were more involved with. 

Mr. DINGELL. Now Senator, do you believe that the primary reviewers, the whistle-blowers that came to your committee and testified here last year, raised appropriate concerns about the safety 

and efficacy of Ketek? 

Senator GRASSLEY. Of course. They are a major source of information on this specific case. But I want to point out, to encourage 

whistle-blowers everywhere in government, that they are a very 

important part of the process of congressional oversight. We can’t 

know where all the skeletons are buried, and we want to find out 

where those skeletons are, not just in this administration but every 

administration in the past when it has been difficult, and in the 

future. 

Mr. DINGELL. We happen to agree very strongly on that, Senator. 

Now, if the investigators did a good job in detecting problems 

and the reviewers did a good job in assessing their implications, 

what does this say about the supervisors in CDER, that is the Center for Drug Evaluation and Research? 

Senator GRASSLEY. Well, it seems to me that they were not doing 

their job. 

Mr. DINGELL. It seems to be very clear from the record here. 

Now, Senator, you referred to Dr. Victoria Hampshire. And you 

have indicated that she is essentially a whistle-blower who is now 

being, quite frankly, inquired into in ways that I think you indicated are less than fully correct by FDA and by the Justice Department and others. 

Senator GRASSLEY. Yeah, and by a company that worked with 

FDA to implicate her. 

Mr. DINGELL. Would you want to tell us a little bit more about 

that? 

82 

Senator GRASSLEY. Well, for instance, we know of an instance in 

which there was a PowerPoint program put together to come in to 

show why Dr. Hampshire ought to be fired. 

Mr. DINGELL. I think we will be asking for that. 

Senator GRASSLEY. Would you please contact my staff in regard 

to the details of that? 

Mr. DINGELL. I would certainly do so. 

I wanted to ask you, Senator, because I think this is an important question, you did a superb job as Chairman of the Finance 

Committee and we have much to thank you for for your labors on 

this particular matter. Would you suggest that this committee 

ought to have a look maybe at the behavior of FDA with regard to 

Dr. Hampshire? 

Senator GRASSLEY. I would. It would be very helpful, because you 

as the Chairman will get the attention much more than a Ranking 

Member, even considering I am in the higher body. 

Mr. DINGELL. We will try and get their attention. And I think 

working together we can perhaps procure some more focused and 

proper care, concern and attention at FDA. Senator, it is a privilege to see you again. 

Mr. STUPAK. Thank you, Senator. 

Mr. DINGELL. And thank you for your courtesy to me, Mr. Chairman. 

[The prepared statement of Senator Grassley follows:] 

STATEMENT OF SENATOR CHUCK GRASSLEY

Chairmen Dingell and Stupak, Ranking Members Barton and Shimkus, and distinguished colleagues, thank you for inviting me to speak today about my investigation of FDA’s handling of the large safety study Ketek, Study 3014. It has been a 

long road and it’s still not at an end. 

More than two years ago, in January 2006, the journal Annals of Internal Medicine reported three cases of liver damage in North Carolina patients who took 

Ketek. In response the FDA issued a public health advisory. 

After all, suffering severe liver problems is quite a price to pay for taking an antibiotic that was being used for such conditions as sinus infections until that indication was removed from the Ketek label a year ago. 

Soon after, I heard allegations and concerns regarding FDA’s review of Ketek and 

I started asking questions. One of the more serious allegations was that the maker 

of Ketek, Aventis at the time, submitted clinical trial data to the FDA in support 

of approval, knowing it was fraudulent. 

So I asked FDA to make arrangements immediately for my staff to review documents related to Study 3014 at the FDA’s offices. 

Initially, FDA gave my staff access and agreed to provide copies of documents my 

staff identified during their review. 

But then I asked for Special Agent Robert West from FDA’s Office of Criminal 

Investigations and the FDA pulled a 180 on me. 

I had good reasons for asking for Agent West. One of the other allegations I received was that despite Agent West’s concerns and recommendations, FDA never expanded its investigation to determine if the company did ‘‘knowingly’’ submit fraudulent data. 

Agent West played an integral role in the investigation of Study 3014 and I am 

delighted to see that he will be testifying on the next panel along with two other 

special agents from the agency. Agent West was the lead agent on the investigation 

of Dr. Anne Kirkman Campbell, one of the principal clinical investigators for Study 

3014. And as a result of that investigation Dr. Kirkman Campbell is currently serving a 57-month prison sentence. Agent West also was in frequent communication 

with the FDA consumer safety officers and reviewers involved in the Study 3014 

inspections. 

But as I testified before this subcommittee a year ago, FDA and HHS wouldn’t 

make Agent West available-even after I went over to the HHS offices to ask personVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00086 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
83 

ally to speak with Agent West and subpoenas were issued. After all, if FDA had 

nothing to hide about how it handled Study 3014, why stop me from talking to 

Agent West? I smelled a ‘‘cover-up.’’ 

Well, I now have a better understanding of why FDA did not want me to speak 

to Agent West regarding Ketek. The answer to the ‘‘WHY’’ question is equally interesting. It seems to me that there were definitely reasons why the FDA did not want 

me to meet with Agent West or any other agents for that matter. FDA, it appears, 

did not want anyone to know that it didn’t further investigate whether or not 

Aventis submitted fraudulent data knowingly to the FDA. The FDA did that even 

though Agent West recommended, in the summer of 2003—almost 5 years ago—to 

high level officials at the FDA that it needed to create a mini-task force look into 

Aventis. 

When HHS and FDA finally made Agent West available a short time ago—18 

months after I first requested him—Agent West confirmed that no one acted on his 

recommendations. In fact, I learned from HHS more than a year after my visit to 

the Department, that the FDA didn’t open an investigation into the company until 

March 2006. Interestingly, that was around the same time I started poking around 

Ketek. 

Agent West told his supervisors, FDA investigators involved in the Study 3014 inspections, as well as FDA directors overseeing the review of Ketek what he thought 

needed to be done—inspect all the study sites that enrolled over 100 patients. The 

protocol for Study 3014 had recommended a maximum enrollment of 50 patients per 

site, so that would have meant inspections of about 70 sites. 

Agent West’s supervisors told my staff that they supported him. The site investigators also thought it was a good idea. But what happened? 

The head of the Office of Criminal Investigations told my staff that Agent West’s 

concerns and recommendations were referred up the food chain, and he assumed the 

matter would be taken care of. 

The Associate Commissioner for Regulatory Affairs at that time said he was prepared to offer any assistance if needed but never heard anything more from the Office of Criminal Investigations. 

One of Agent West’s superiors said the CDER folks were briefed so the ball was 

in their court. He also said that Agent West’s task force proposal had nothing to 

do with concerns about Aventis. 

But I have since learned that that’s not true. 

Agent West sent an email in July 2003 to his superiors about his conversation 

with directors in FDA’s Center for Drug Evaluation and Research. These directors 

oversaw the review of Ketek. 

In that email, Agent West said, ‘‘I told them that it was my opinion that Aventis 

knew sites were suspect but did nothing to prove or refute their suspicions.’’ 

Agent West was not the only agent who believed that the company or at least 

someone within the company knew there were serious problems, particularly at Dr. 

Kirkman Campbell’s site. You have the two agents here today who were assigned 

to the criminal investigation that was opened in March 2006—Special Agents Robert 

Ekey and Douglas Loveland. 

Agent Ekey said during a joint interview with our Committees that he thought 

the company too easily dismissed the concerns that were raised by its own contract 

research organization, the organization hired to monitor Study 3014. 

Agent Loveland wrote in an internal email dated April 17, 2007, that the company 

knew significant issues existed at many sites yet the company submitted the data 

to the FDA and claimed the study was conducted according to good clinical practices. He also told my staff during an interview yesterday that Aventis should have 

known that there were problems with the integrity of the study data. 

The case was closed in July 2007. FDA issued a warning letter in October to the 

company for failing to ensure proper monitoring of Study 3014 and not adequately 

investigating allegations of fraud at Dr. Kirkman Campbell’s site. The letter cited 

many of the same problems that FDA’s staff raised back in 2003 and 2004. So why 

wasn’t an investigation initiated then? 

Agent West stated in his July 2003 email, ‘‘I think the three individuals in CDER 

understood my feelings and opinions but I don’t know whether or not the necessary 

steps will be accomplished.’’ 

When my staff spoke with the three directors, one of them told my staff that if 

the Office of Criminal Investigations wanted additional investigations, it was their 

call, not CDER’s. He also said that the Office of Criminal Investigations should have 

talked to the Division of Scientific Investigations since the division oversees clinical 

trial site inspections. 

So who’s responsible? 

84 

Everyone seemed to be pointing the finger at someone else, with the exception of 

the head of FDA’s office of Division of Scientific Investigations. This FDA employee 

told my staff that as far as additional inspections went, they didn’t have the resources to do more. And besides, she said (1) the FDA didn’t rely on Study 3014 

for approval, (2) FDA completed 8 site inspections for Study 3014, which is many 

more than the one or two it normally does, and (3) astonishingly, she also said that 

investigating drug companies is a ‘‘losing game’’ and the chances ofgetting a warning letter is zero. 

I find that attitude extremely troubling, as I’m sure you do as well. 

We rely on the FDA to ensure that the drugs in our medicine cabinets are safe 

and effective. That includes FDA making sure that the data supporting the safety 

and efficacy of a drug is sound. To do that adequately, FDA has to do its job of oversight over clinical trials. Data integrity isn’t the only issue of concern here. FDA 

also has an obligation to protect human subjects. 

In December, I raised this matter to Commissioner von Eschenbach in a lengthy 

letter regarding my Ketek investigation. That letter I’ve been told is included in 

your exhibit books. I asked Commissioner von Eschenbach: If it is FDA’s position 

that no additional inspections are required once a study is no longer useful for regulatory action, then how can FDA protect research subjects from the harm that may 

be caused by clinical investigators? 

Not relying on a study for approval does not absolve FDA of its responsibility to 

protect the individuals who courageously volunteer in clinical trials so that we can 

all benefit from lifesaving cures and medical innovation. I am still waiting for the 

Commissioner’s comments on this important matter. 

Of course, this responsibility does not lie only with the FDA. The drug companies 

also have a responsibility to the people who participate in their clinical trials. They 

also need to ensure that problems are adequately investigated and addressed. 

In the case of Study 3014, there were sirens, red flags and bull horns, but it looks 

like the company and the FDA kept ear plugs and blinders on. 

I like to close by saying that it troubles me that the FDA failed to act on the serious concerns raised by Agent West until almost 2 years after Ketek was approved 

and almost 31⁄2 years after Study 3014 was submitted to the FDA. It troubles me 

that an FDA manager would say that investigating a company is a ‘‘losing game’’ 

because in the case of Ketek, after the FDA did do the investigation, a warning letter was issued. This same individual, however, hasalso said that more oversight of 

clinical trials was needed. 

FDA officials have told me that some initiatives are underway, including making 

sure that there’s proper oversight and authority over all the parties involved in clinical trials. I hope we see significant improvements in the near future. 

There’s also been a lot of talk over the last several months about FDA inspections, 

especially foreign inspections. FDA has limited resources to perform this important 

function. Just as more and more drugs are being manufactured overseas, more and 

more studies are being conducted outside of the United States. 

I look forward to working with this Committee and in particular with you, Chairmen Dingell and Stupak and Ranking Members Barton and Shimkus, as well as my 

colleagues in the Senate to ensure that FDA has the resources and tools to do its 

job. 

Thank you. 

Mr. STUPAK. Let’s call back our last panel that was up there. 

Third panel, Dr. Paul Chew, Dr. Fred Eshelman, and Ms. Sharon 

Hill Price. 

Dr. Chew, Dr. Eshelman and Ms. Sharon Hill Price, you are remaining under oath, understood? OK. 

Ms. Price, let me ask you this. What is the purpose of an IRB? 

What is the main focus of an IRB? 

Ms. PRICE. An Institutional Review Board, or IRB as it is called, 

review clinical research within an ethical and regulatory framework to assure—— 

Mr. STUPAK. To protect—— 

Ms. PRICE. Yeah, to assure subject protection according to regulation. 

Mr. STUPAK. Assure patient safety. 

85 

Ms. PRICE. Subject safety, yes. 

Mr. STUPAK. OK. So if there was a concern about patient safety, 

instead of PPD, the contract review organization, they would go to 

the IRB, correct? 

Ms. PRICE. We are one of the venues, yes, if there is concern 

about subject safety. 

Mr. STUPAK. What other venue is there? 

Ms. PRICE. I think subject safety is a shared responsibility, as I 

indicated in my opening statement. 

Mr. STUPAK. With the IRB, Copernicus in this case on Study 

3014, and who else? 

Ms. PRICE. The sponsor, the investigator. 

Mr. STUPAK. That would be Aventis. 

Ms. PRICE. The investigator. 

Mr. STUPAK. That would be Dr. Kirkman-Campbell. 

Ms. PRICE. And the FDA. 

Mr. STUPAK. The FDA. 

Ms. PRICE. Even the subject to some extent needs to take some 

responsibility for participating in research. 

Mr. STUPAK. Sure. But the main focus, the reason why IRBs 

came about was to protect patient safety. Correct? 

Ms. PRICE. Yes. 

Mr. STUPAK. And that is the genesis of the IRB, is patient safety? 

Ms. PRICE. Yes. 

Mr. STUPAK. OK. And you said you had 83 complaints when I 

was asking you questions before just on Kirkman-Campbell, right? 

Ms. PRICE. Yes, we had 83 memos to file submitted 3 months 

after she closed. 

Mr. STUPAK. Right. And you said it was 90 days after KirkmanCampbell closed out her work on Study 3014. Correct? 

Ms. PRICE. Correct. 

Mr. STUPAK. Did you ever read any of those 83 memos that came 

to the file? 

Ms. PRICE. Only recently. 

Mr. STUPAK. So while 83 memos came in, you weren’t curious to 

see what the violations were? 

Ms. PRICE. They were in a file with 3,300 other investigators, 

and, at the time, our policy and procedures was not to review those 

protocol deviations. 

Mr. STUPAK. Well, how do you ensure patient safety then if you 

don’t know what the memos and violation are saying. 

Ms. PRICE. It was not our policy at the time to review those. 

Mr. STUPAK. But isn’t that why an IRB comes in fruition? Isn’t 

that why they were created, was to protect patient safety? You get 

83 memos in and you don’t look at them? 

Ms. PRICE. That was our policy at the time. And we have since 

revised that. 

Mr. STUPAK. Well, why would Aventis or anyone hire an IRB if 

it wasn’t to have patient safety as their goal and their mission? 

Ms. PRICE. The regulations require the review of clinical research 

by an institutional review board. 

Mr. STUPAK. Right. Its main purpose is patient safety? 

Ms. PRICE. Correct. 

86 

Mr. STUPAK. So why would anyone hire Copernicus if you’re reviewing the files? 

Mr. DINGELL. Would you yield? I just wanted to note that I very 

much appreciate this hearing and I very much appreciate the work 

you’re doing here in this matter and I’m listening most attentively 

to the matters you’re discussing. 

Mr. STUPAK. Well, thank you. Well, are you not as an IRB, Copernicus, are you not responsible for reporting noncompliance to 

the FDA? 

Ms. PRICE. Yes, we are. According to our— 

Mr. STUPAK. You may want to wait a minute here. It’s going to 

ring for a second. OK. 

Ms. PRICE. Issues that rise to the level of noncompliance or investigator noncompliance would be reportable to the FDA according 

to the regulations. 

Mr. STUPAK. So did you report to the FDA? You had 83 violations 

alone just on Kirkman-Campbell. Did you report to the FDA? 

Ms. PRICE. No. We had no obligation at that point to report any 

of those violations. 

Mr. STUPAK. Why wouldn’t you have an obligation, you’re the 

IRB? 

Ms. PRICE. We received that information 3 months after her site 

was closed out. 

Mr. STUPAK. No, you received the memo that we talked about, 

memo number 33, it’s Exhibit No. 33, the one from Ms. Cisneros 

to Ms. Wallace, you received that. Didn’t you have a responsibility 

to report that to the FDA? 

Ms. PRICE. It was human error that that didn’t get elevated as 

it should have been. 

Mr. STUPAK. Well, besides this one right here, you had 83 more 

complaints about Kirkman-Campbell. You didn’t report those to the 

FDA? 

Ms. PRICE. I want to clarify something, if you don’t mind, on a 

former answer. We did not become aware of this telephone contact 

report until January 23, 2008, at which time you all were immediately notified. 

Mr. STUPAK. Wait a minute. You testified earlier you became 

aware of an electronic format that was in the electronic files in 

2006. 

Ms. PRICE. As we reviewed our information, it did show up on 

our electronic report. However, we did not generate that report for 

Grassley’s committee. It did not appear in our hard copy files. And 

we did not see that memo. No one opened that memo until January 

23, 2008, one hour before you all received it. 

Mr. STUPAK. OK. Well, then let’s go over this again then. Kyle, 

do you have that exhibit? Let me show you a letter of February 27, 

2007, from this Committee signed by Mr. Dingell and myself, addressed to you as executive officer and chairman of the Copernicus 

Group. Do you have that document, Kyle? I think your counsel has 

it right there. He’s handing it to you. OK? 

Ms. PRICE. Yes, sir. 

Mr. STUPAK. We’re asking for certain documents. It goes to page 

2, top of the page, adverse events reported to Copernicus relating 

to the subjects in Study 3014 regardless of the source of these reVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00090 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
87 

ports. You indicated you knew it existed electronically in about 

2006 at the request of Senator Grassley’s request. Now you’re telling me today you didn’t realize that Exhibit 33 existed until 2008. 

So for almost a year you sat on it without giving us the information 

we requested, right? 

Ms. PRICE. No one had opened the document. After we received 

this letter dated February 27, 2007, our counsel met with your staff 

and decided—— 

Mr. STUPAK. And your counsel or you did not tell us about this 

electronic file that you never opened, right? 

Ms. PRICE. Excuse me? 

Mr. STUPAK. You or your counsel never told us about the electronic file? 

Ms. PRICE. We didn’t know it existed. We only knew that after 

we investigated how this thing turned up now, because we thought 

that it was—— 

Mr. STUPAK. So you expect me to accept you knew the report was 

there in 2006, you saw it for Grassley when Senator Grassley 

asked, but you expect me to accept the fact that since you didn’t 

open it you had no obligation to produce it to us? 

Ms. PRICE. I think we had an obligation if we would have opened 

it, but we did not and I’m sorry for that. 

Mr. STUPAK. So to get around a request you just don’t open the 

file? 

Ms. PRICE. Not intentionally. 

Mr. STUPAK. I mean, the U.S. Senate asks, we ask, and then the 

day you manage—how is it you come to think about it the day before you’re brought in before the committee? 

Ms. PRICE. It was discovered the day before I was to meet with 

your subcommittee or your staff, sir. 

Mr. STUPAK. Right. It was discovered earlier in 2006, but you 

just don’t remember it until the day before you come to the committee. Isn’t that a coincidence? 

Ms. PRICE. After further investigation it did appear in an electronic search for Grassley, but it wasn’t prepared for Grassley. 

Mr. STUPAK. Then let’s go back to what I was just asking you 

about. Are you responsible for reporting and you never reported 

anything to the FDA about these 83 reports or this report, Exhibit 

No. 33, from Ms. Cisneros, the telephone call to you? And you’re 

responsible for reporting noncompliance to the FDA, correct, that 

is established, right? 

Ms. PRICE. Yes, sir. 

Mr. STUPAK. And all these reports you had, the 83, this one from 

Ms. Cisneros, you did not give that to the FDA, correct? 

Ms. PRICE. Correct. It did not rise to the level of any anticipated 

problems at that point in our history in 2002. 

Mr. STUPAK. That’s your judgment? 

Ms. PRICE. That was our policy and procedure at the time. 

Mr. STUPAK. Well, you’re familiar with 21 C.F.R. 56, the IRB 

functions and operations, right? 

Ms. PRICE. Yes, sir. 

Mr. STUPAK. Does it not say in that that any instance of serious 

or continuing noncompliance with these regulations or the requireVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00091 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
88 

ments or the determinations of the IRB, are you not required to report that to the FDA in order to fulfill requirements—— 

Ms. PRICE. It does say that in words to that effect. I believe so. 

Mr. STUPAK. OK. So you violate this policy, too? 

Ms. PRICE. No sir, I don’t believe we do. That’s your opinion and 

I don’t share that opinion. 

Mr. STUPAK. So you don’t feel you have to follow 21 C.F.R. 56, 

Section 108, subsection (b), IRB functions and operations? 

Ms. PRICE. We do follow up 21 C.F.R. We received 83 memos to 

file 3 months after an investigator closed and we had no obligations. 

Mr. STUPAK. Your responsibility doesn’t stop when Ms. Kirkman 

stops the study; it continues. 

Ms. PRICE. According to the regulations, we review investigators 

and have that authority through the time that we’re overseeing 

them as IRB of record. Once they have a final status report they 

are closed. 

Mr. STUPAK. Well, when is the final study status closed, when 

it’s presented to the FDA? 

Ms. PRICE. No, sir, when they close at our site—when they close 

the IRB. 

Mr. STUPAK. So once the site closes you have no more responsibility to report problems with patient safety? 

Ms. PRICE. We have no regulatory obligation, no. 

Mr. STUPAK. How about legal obligation under 21 C.F.R. 56? 

Ms. PRICE. Our interpretation of that regulation would not have 

indicated that we would have needed to provide those. 

Mr. STUPAK. Well, that’s your interpretation. How about moral 

obligation to the patients? If your IRB is there to protect patient 

safety, don’t you have a moral responsibility if you have questions 

on patient safety to report it to the FDA or to Aventis or to the 

PPD? 

Ms. PRICE. I started this company in 1996 and I have the utmost 

respect for the regulations and have run my business providing 

ethical review. And I do have obligations, according to our standard 

operating procedures, which we had in place at the time, and I felt 

that it met the requirements. 

Mr. STUPAK. I’m not asking about standard operating procedures. 

I’m asking you if you have a moral obligation since you’re responsible for patient safety when you see 83 reports just from one site 

to report that to somebody, like the FDA to Aventis or PPD? 

Ms. PRICE. Aventis sent them to us and PPD sent them to us, 

so they were already aware of them. 

Mr. STUPAK. OK. Well, how about do you have a moral obligation 

to the FDA? 

Ms. PRICE. Not at the time, according to our standard operating 

procedures. 

Mr. STUPAK. How about today, do you have a moral obligation to 

the FDA to report documents to them that refer to patient safety? 

Ms. PRICE. If something came in similar to this today, number 

one, we revamped our standard operating procedures. And as I 

said, information about unanticipated problems is more clearly understood across the board for institutional review boards. I feel confident that anything that would come in today that would rise to 

89 

this level would be reported appropriately to the board and they 

would make a determination on what should be done, which would 

probably include notifying the FDA. 

Mr. STUPAK. Did you have reports from other sites other than 

Kirkman-Campbell? 

Ms. PRICE. What type of report, sir? 

Mr. STUPAK. On patient safety issues, protocol violations. 

Ms. PRICE. There were a number of memos to file. I would anticipate that there would have been others, yes. 

Mr. STUPAK. So you don’t know if there were others. Do you anticipate there were others? 

Ms. PRICE. I know that there were memos to file. I don’t know 

the specifics of the contents of those. 

Mr. STUPAK. Well, did you report any of those violations to the 

FDA? 

Ms. PRICE. No, sir. We weren’t reviewing protocol deviations or 

memos to file at that point in 2002. 

Mr. STUPAK. So all these things come in and it was your standard operating procedure not to report these violations to the FDA 

or anybody? 

Ms. PRICE. That’s right. 

Mr. STUPAK. So what are you there for? Why do you exist? 

Ms. PRICE. IRBs perform a very integral part of a role in—— 

Mr. STUPAK. I agree. I’ve done many hearings on IRBs. Their 

main focus is to protect patient safety. IRBs started in the university setting, in a public setting, but now they’ve gone to outside the 

private, for-profit groups like yourself. And if we don’t hit the nail 

right on the head on standard operating procedures you just feel 

you have no responsibility for patient safety. 

Ms. PRICE. I disagree. We work very closely within an ethical 

and regulatory framework as put out. 

Mr. STUPAK. When I asked about the ethics you didn’t have an 

answer. You just said that was in your standard operating procedures and under 21 C.F.R. You didn’t think you had any legal responsibility. So where do the ethics come in now? 

Ms. PRICE. We review everything. Our board reviews everything, 

according to the Belmont Report, the ethical principles in the Belmont Report, which talk about autonomy of individuals, which 

talks about risk benefit association and also it talks about distribution of justice. 

Mr. STUPAK. The bottom line, you blew it here, right? You didn’t 

do your job here, on this study, correct? Is that fair to say? 

Ms. PRICE. We had a human error in not addressing this call 

from an investigative site monitor. 

Mr. STUPAK. Not just a call, but the 83 other violations and the 

other violations from other sites are reported to you, you had a responsibility to tell the FDA and you didn’t say anything to the FDA 

on any of them? 

Ms. PRICE. I’m sitting here today telling you that I think we did 

a good job for what we did at the time. 

Mr. STUPAK. Good job of saying nothing to the people who need 

to know, which was the FDA, right? I don’t mean to be argumentative but this is ridiculous. Mr. Chairman, you had a couple questions on IRBs you want to ask? 

90 

Mr. DINGELL. Mr. Chairman, I think you’re raising more questions than we’re getting answers to. The witness here that you’ve 

been just inquiring of, what is the name of your firm, ma’am, if you 

please? 

Ms. PRICE. Copernicus Group IRB. 

Mr. DINGELL. What is your relationship to that company? 

Ms. PRICE. I’m the founder and CEO. 

Mr. DINGELL. How many employees do you have? 

Ms. PRICE. We currently have about 70 employees. 

Mr. DINGELL. What is the net worth of the company? 

Ms. PRICE. Net worth meaning? 

Mr. DINGELL. What’s the net worth? 

Ms. PRICE. I would say in the millions of dollars. 

Mr. DINGELL. Now, tell me, how long has the company been in 

existence? 

Ms. PRICE. I started the company in 1996. 

Mr. DINGELL. Are you a publicly held company? 

Ms. PRICE. No, sir, privately held. 

Mr. DINGELL. Privately owned? 

Ms. PRICE. Yes. 

Mr. DINGELL. Do you file annual reports with anybody? 

Ms. PRICE. We file taxes. 

Mr. DINGELL. Taxes, that’s all? 

Ms. PRICE. And annual corporate reports. 

Mr. DINGELL. You don’t file any reports to the SEC or any of the 

State regulatory agencies? 

Ms. PRICE. No, sir. 

Mr. DINGELL. What was your earnings last year? 

Ms. PRICE. Earnings last year? Revenue top line was about $13 

million. 

Mr. DINGELL. And from where did you earn that $13 million? 

Ms. PRICE. A number of clients. 

Mr. DINGELL. From what? 

Ms. PRICE. A number of clients and sponsor organizations that 

submitted studies to us. 

Mr. DINGELL. You earned it then functioning as an IRB? 

Ms. PRICE. Yes, sir. That’s the basic function of the company. 

Mr. DINGELL. Did you earn money from any other source? 

Ms. PRICE. No, sir. 

Mr. DINGELL. Now, how are you retained to do this work? Are 

you retained by the companies that have these matters before Food 

and Drug or does Food and Drug appoint you or how are you appointed? 

Ms. PRICE. In the case of Kirkman-Campbell or in the case of 

3014 we were contacted by the CRO. We are usually paid by the 

sponsor companies, and that would be like the pharmaceutical 

sponsors. 

Mr. DINGELL. So you’re paid by the sponsor company, but by 

whom are you selected? 

Ms. PRICE. The pharmaceutical company or their designee, which 

would be sometimes CROs select us, or investigators sometimes approach us to serve as an IRB of record for their studies. 

Mr. DINGELL. How many companies do you work for? Could you 

submit us a list of the companies for whom you have worked? 

91 

Ms. PRICE. Yes. 

Mr. DINGELL. And could you submit us also a list of the companies to whom you have provided or rather—by whom you have 

been paid and for what, to what, let’s see, for what, for inquiries 

in what matters were you paid by what companies over the period 

since this matter of Ketek? And starting with Ketek and those matters and the years in which you worked on that going forward, 

what companies—would you submit to us what companies you 

have worked for as an IRB? 

Ms. PRICE. Certainly. You’re asking for a list of studies we have 

reviewed since 2001? 

Mr. DINGELL. Yes. I want it going back to the year on which you 

worked with or for Ketek, the companies. 

Ms. PRICE. Yes, I can do that. 

[The information was not submitted for inclusion in the record.] 

Mr. DINGELL. And how much you were paid on each. And on 

which matters and on which pharmaceuticals you served as an 

IRB. Now, is your company a for-profit or nonprofit company? 

Ms. PRICE. A for-profit. 

Mr. DINGELL. For-profit. And I believe you told me that all you 

do is function as an IRB, is that correct? 

Ms. PRICE. Our basic function is to provide ethical review for 

clinical research. 

Mr. DINGELL. Now, what does this involve? What do you do here 

when you do this? 

Ms. PRICE. Institutional review boards will receive information. 

Are you familiar with protocols? Protocols are actually submitted 

by the sponsor company. We’re usually—protocols and informed 

consent documents are submitted by the sponsor companies. We 

have our board members, who are a group of diverse individuals 

with scientific and nonscientific backgrounds, who review the informed consent documents as well as the protocols. And based on 

the ethical framework of the Belmont Report and the clinical regulations we decide whether there is more risk than—more benefit 

than risk to doing the studies and conducting the research. We 

then take a look at the informed consent document. And we determine whether that information is sufficient for an investigator to 

use to do the informed consent process. The document includes certain things as listed in the regulations, certain elements, letting a 

subject know that they can voluntarily be in the study and come 

out, back and forth, at any time, risk benefits and that sort of 

thing. 

Mr. DINGELL. Now, tell us, do you review testimony or review 

documents that are submitted by the company in connection with 

the questions before Food and Drug? Do you review the competence 

or the qualifications of the persons who are doing the research or 

presenting papers or testimony? 

Ms. PRICE. Yes. Per the regulations, the investigators are selected by the sponsor company. And part of our review is to look 

at the submission packet for the investigators. And in the case of 

Study 3014 we did spot checks of licensure. 

Mr. DINGELL. I’m trying to understand here with more than a little difficulty exactly what you do. 

92 

Ms. PRICE. I think that institutional review boards have always 

had difficulty explaining what they do. I wish I could explain it better. We review clinical research from an ethical perspective. We are 

not on the ground monitoring at the investigator site. We try to assure the subject safety through ethical review. 

Mr. DINGELL. You do an ethical review? 

Ms. PRICE. Yes, sir, of the protocol, the informed consent document. 

Mr. DINGELL. What is an ethical review? What constitutes an 

ethical review? 

Ms. PRICE. We base our ethical review on the Belmont Report, 

the issues released in the Belmont Report. And those are ethical 

principles that reflect the conduct of good clinical research. As I 

stated before, that has to do with autonomy of subjects, making 

sure that there is an informed consent process that takes place. We 

look at the research or the IRB will look at the research and determine if there is enough benefit to do the study, if something, 

generalizeable knowledge can come out of it. And thirdly, we look 

at justice. Is the—is there one group that is receiving most of the 

burden of research or is it equitable across the board. In addition, 

our IRB will look and see that there is a monitoring plan in place, 

that there is going to be some type of monitoring for the study. 

Then ongoing investigators are obligated per the regulations to 

submit—— 

Mr. DINGELL. Does your work require you or permit you to look 

to see whether the data is true, factual and correct? 

Ms. PRICE. No, sir, we don’t deal with data. 

Mr. DINGELL. Now, how do you make an ethical review without 

knowing whether or not the information received is true, factual 

and correct? 

Ms. PRICE. That is not our role. 

Mr. DINGELL. That’s not your role. 

Ms. PRICE. No, sir. 

Mr. DINGELL. Do you look to see whether the proper information 

has been submitted to support the allegations and the statements 

made either by Food and Drug or by the applicant? 

Ms. PRICE. No, sir. That’s a monitoring function that’s the responsibility of the sponsor. 

Mr. DINGELL. Do you look for whether false statements are made 

in connection with the application or whether the studies that are 

submitted are in fact valid, truthful, factual, correctly and honestly 

done? 

Ms. PRICE. No, sir, we don’t per se. 

Mr. DINGELL. Do you do that? 

Ms. PRICE. We rely on the investigators to communicate with us. 

And in this case sponsors. 

Mr. DINGELL. So then do you know whether the studies that are 

submitted as a part of your ethical evaluation are factual, truthful, 

correctly done? 

Ms. PRICE. We don’t have a role after the study is completed to 

follow up on the analysis of the data or the submission to the FDA. 

Mr. DINGELL. Now, you got $375,000 for this matter, I believe, 

is that right? 

Ms. PRICE. Yes, sir. That was how much we made off the study. 

93 

Mr. DINGELL. Exactly what did you do for this $375,000? 

Ms. PRICE. We reviewed the protocol, the informed consent document. 

Mr. DINGELL. You reviewed what? 

Ms. PRICE. We reviewed the protocol, the informed consent document, we reviewed investigator packets and we looked at serious 

adverse events as they came in. We fashioned an informed consent 

document that was to be used by investigators for the informed 

consent process. 

Mr. DINGELL. Did you ever go into the question of whether or not 

the studies were factual or adequate? 

Ms. PRICE. That determination was made—I’m a little unclear on 

your factual comment. But certainly the assessment of the institutional review board members themselves would have gone into 

whether they felt the study was designed in an appropriate way 

and would—— 

Mr. DINGELL. Did you ever interview anybody about the studies 

as to whether they were factual or correctly done or included all 

the persons that should have been interviewed or whether or not 

all the persons upon whom the tests were supposed to have been 

performed were either properly treated or in fact existed or had 

had the results that would indicate a proper study? 

Ms. PRICE. No, sir, we didn’t interview anyone. 

Mr. DINGELL. Did the Ketek study comply with the Belmont review? 

Ms. PRICE. In the opinion of the institutional review board, yes, 

it met the requirements, yes, sir. 

Mr. DINGELL. It did. 

Ms. PRICE. Yes, sir. 

Mr. DINGELL. Why do you say that? 

Ms. PRICE. Our board is trained to look for certain things. And 

they use the Belmont Report for their guidance, and then the regulations. And our preliminary review is initially to review the protocol and informed consent document. 

Mr. DINGELL. Now, could you pass the Belmont review and still 

have fraud? 

Ms. PRICE. A study could certainly be approved. And it was in 

this case. The study was approved on the Belmont principles; however, there was fraud by an investigator or investigators in the 

study. 

Mr. DINGELL. So you couldn’t ask the Belmont review if there 

was fraud there, is that right? 

Ms. PRICE. Yes. 

Mr. DINGELL. Can you make the bold statement that there was 

no fraud in connection with Ketek or any of the studies that were 

made with regard to the approval of their applications by Food and 

Drug? 

Ms. PRICE. Can I make the statement that there was no fraud? 

I think that it has been found that there was fraud. 

Mr. DINGELL. Say that again. 

Ms. PRICE. There has been found that there was fraud. 

Mr. DINGELL. There was fraud. 

Ms. PRICE. According to the Food and Drug Administration, yes. 

Mr. DINGELL. I’m sorry. 

94 

Ms. PRICE. According to the Food and Drug Administration. That 

was not our assessment. That was the assessment of the FDA. 

Mr. DINGELL. So you don’t know whether there was fraud or not 

or you do know there was fraud? 

Ms. PRICE. According to the FDA there was fraud, so I would say 

yes, there was fraud. 

Mr. DINGELL. And your ethical review did not reveal that there 

was fraud here? 

Ms. PRICE. No, sir, it did not. 

Mr. DINGELL. I find that a curious ethical review. Mr. Chairman, 

I thank you. 

Mr. STUPAK. Thank you, Mr. Chairman. Mr. Barton for questions. We’ve been going around more than once for this panel since 

we’re only on Ms. Price, it seems like. 

Mr. BARTON. Thank you, Mr. Chairman. I apologize. I’ve been 

stuck in airports most of the day. My plane was delayed, so I’ve 

not been able to attend the entire hearing. My questions are going 

to be for Dr. Eshelman. It’s my understanding, Doctor, that the 

Aventis PPD contract for this Study 3014, that Aventis was responsible for bringing the investigators into compliance; if that wasn’t 

possible, terminating their participation in the study. Is that your 

understanding? 

Mr. ESHELMAN. PPD was not responsible for the termination of 

an investigator, if I understood your question. 

Mr. BARTON. Well, the question is the staff has informed me that 

Aventis was responsible for bringing investigators into compliance, 

but if they couldn’t do it, then Aventis had to terminate their participation into the study? 

Mr. ESHELMAN. That’s correct, sir. 

Mr. BARTON. Did the contract specify which party should notify 

FDA in the event that it did discover fraud? 

Mr. ESHELMAN. I think that the regulatory communication function was retained by Aventis under the terms of the contract. 

Mr. BARTON. Did anything in the contract prevent your company, 

PPD, from notifying FDA about your concerns? 

Mr. ESHELMAN. I guess only under the terms of confidentiality as 

they might or might not have applied. I mean there was certainly 

nothing explicit or implied by Aventis or anyone else that would 

have otherwise prevented us from contacting a regulatory body 

with the exception of the particular retention by Aventis of regulatory communication in this instance, which is a long-winded way 

of saying all that stuff notwithstanding we could still do whatever 

we wanted to. 

Mr. BARTON. In other studies that PPD has been involved with 

with the FDA, has your company ever notified the FDA about 

fraud when it wasn’t directed to do so by the particular drug sponsor? 

Mr. ESHELMAN. I can’t say with assurance because I don’t have 

the facts in front of me. But on occasion PPD is assigned all of the 

responsibilities for a particular study, including communication 

with regulatory bodies. And in such an instance if there were reason for disqualification of an investigator we certainly would communicate that with FDA and other appropriate bodies. I don’t know 

whether we have specifically done that or not. I certainly know 

95 

that in the course of our work over the years we have made recommendations to sponsors on a large number of issues. And sometimes they are followed through and sometimes they’re not because 

sometimes there is a bona fide difference of opinion on a site. 

Mr. BARTON. Please describe your company’s role in vetting physicians for participation as clinical investigators. Do you rely on the 

FDA debarment and disqualification list as part of your vetting? 

Mr. ESHELMAN. Yes, sir. And we screen investigators against 

that list all of the time. And it’s typical that when we contract with 

a company like Sanofi-Aventis we warrant that in fact we have 

done that. When we sign up investigators, also we try to qualify 

them on a basis of their training and experience. We also request 

a copy of the medical license that is valid at that time. 

Mr. BARTON. Do you conduct any other research to determine 

whether the physician has been convicted of a felony relating to a 

drug product? 

Mr. ESHELMAN. My assumption is that if a physician has been 

convicted of a felony, their license would be revoked. Now, I’m not 

a lawyer, I don’t know if that’s true. That’s my assumption. 

Mr. BARTON. Well, I mean the basic question is do you do any 

outside independent research or do you rely strictly on the list that 

the FDA provides in terms of debarment and disqualification? 

Mr. ESHELMAN. No, sir. We get a copy of their current medical 

license. I’m also informed that post, I think 2004, we became aware 

of certain Web sites that we could go to, which would indicate 

whether or not there had been sanctions by medical licensure 

boards against particular physicians. So we can also go to those in 

most States. I believe that maybe this is not true in Wisconsin, but 

in most States it is. 

Mr. BARTON. I’m a little bit confused. Is all you basically do, you 

do a status check on the license that the physician under review 

for participation, that that license is current, is that the extent of 

your investigation? 

Mr. ESHELMAN. No, sir. We also look at their curriculum vitae 

to be sure that they are in fact trained appropriately for what they 

are supposed to do. 

Mr. BARTON. Do you believe that the debarment and disqualification lists that the FDA provides accurately reflect the number of 

individuals who have been convicted of crimes relating to drug 

products? 

Mr. ESHELMAN. Based on the testimony that I’ve heard today 

with particular reference to Dr. Kirkman-Campbell, I guess I would 

have to say no. 

Mr. BARTON. Well, we’re releasing a report today, if we haven’t 

already, that shows that the FDA has been hardly stalwart in pursuing debarment even when the factual and legislative predicates 

are met. Even when they’re mandated do they seem to drag their 

feet. So if we rely on these debarment and disqualification lists as 

provided by the FDA, there are going to be lots of doctors out there 

and lots of folks that probably shouldn’t be allowed to participate. 

And that’s a personal opinion of mine. That’s not necessarily an 

opinion of the committee. 

If what I just said is true, how does that impact your ability to 

screen clinical investigators? 

96 

Mr. ESHELMAN. Well, you know, if the debarment process is 

flawed—— 

Mr. BARTON. Well, it’s almost nonexistent. 

Mr. ESHELMAN. Well, that could present some serious issues for 

us obviously and also sponsors. I’m not sure how that would go to 

our contracts because they, in most cases, do rely on screening 

against this debarment list. But it’s a serious issue. 

Mr. BARTON. My last question, Mr. Chairman. In a conference 

call with Aventis in March of 2002, PPD discussed the problems it 

had identified at Dr. Kirkman-Campbell’s site. According to the 

minutes of that phone call found at tab 5, Aventis tried to take certain steps to identify whether the fraud had occurred. At the time 

of this call, Dr. Eshelman, did you agree with Aventis’ response as 

to how it could address or how it would address the fraud concerns? 

Mr. ESHELMAN. I was not aware of the details of that at that 

time. 

Mr. BARTON. OK. So you had no reason at that time to dispute 

one way or the other Aventis’ concerns? 

Mr. ESHELMAN. No, sir. 

Mr. BARTON. Thank you. 

Mr. STUPAK. No further questions from the ranking member. 

Mr. Markey, a member of the full committee, is here and would 

like to ask some questions of this panel. With unanimous consent, 

I recognize Mr. Markey for 5 minutes for questions. Mr. Markey, 

please. 

Mr. MARKEY. Thank you, Mr. Chairman, very much. Ms. Price, 

after everything that you’ve experienced, what reforms has Copernicus put in place to make sure this does not happen again? 

Ms. PRICE. Thank you for that question. I’ve tried to make it 

clear that we have, we’ve always looked at ways that we can improve our process. 

Mr. MARKEY. How have you improved it? 

Ms. PRICE. We have redone our—or our standard operating procedures have evolved immensely over the past 6 years. We participated in a voluntary accreditation program. 

Mr. MARKEY. Do we need mandatory policies that are on the 

books in terms of how Copernicus and companies like Copernicus 

operate? Should we put mandatory controls on the books that are 

explicit? 

Ms. PRICE. Mandatory controls? The regulations are already in 

place about institutional review boards. I think it would be difficult. Are you asking if there should be mandatory standard operating procedures? 

Mr. MARKEY. To avoid problems in the future should we go back 

and write in specific rules, regulations and laws to make sure that 

there are tighter safeguards in the future? 

Ms. PRICE. I’m not sure how to answer that because I think that 

the regulations are in place and they leave some interpretation. It’s 

definitely open for interpretation. FDA and OHRP are certainly 

trying to—— 

Mr. MARKEY. So you’re saying that the regulations in your opinion just aren’t explicit enough and that they have to be rewritten 

in order to be clear that you are violating a policy, a law, if you 

97 

act in a way that is inconsistent with those regulations? So you 

think we should go back again and rewrite those regulations, is 

that what you’re saying? 

Ms. PRICE. I think that there needs to be some looking at the 

regulations. But no, I’m not saying that we need to rewrite the regulations. 

Mr. MARKEY. OK. I wish that you were saying that, but it would 

be helpful to us that you admitted that there were serious problems that existed. 

Dr. Chew, it is well established that at some point during the 

completion of Study 3014 all of you knew that there were breaches 

in the study protocol. Dr. Chew, did Aventis contact the FDA? 

Dr. CHEW. In the case of Dr. Kirkman-Campbell, no. But in the 

case of two other investigators, yes. 

Mr. MARKEY. Now, Dr. Eshelman, did PPD contact the FDA? 

Mr. ESHELMAN. No, sir, we did not. 

Mr. MARKEY. You did not. And why not? 

Mr. ESHELMAN. Well, first of all, it was a contractual obligation 

reserved by Sanofi-Aventis. Secondly, there was some disagreement 

between the two firms as to whether or not the events at Dr. 

Kirkman-Campbell’s site rose to the level of fraud or if they were 

just GCP violations. 

Mr. MARKEY. Dr. Chew, when did Aventis first become aware of 

the anomalies associated with the study? 

Dr. CHEW. From my review of the record, Congressman, on January 17th or 18th of 2002 an Aventis audit was done. And at that 

time with 327 sites having been randomized, and all informed consents being reviewed, there were issues then raised of dating of the 

consent forms by staff when the informed consent expressly states 

that the dating must be done by the patient. And there were other 

irregularities in the informed consent. There were also issues 

raised at that time of randomization clusters that needed to be 

evaluated, as well as documentation errors, as well as questions 

about the blood sample. 

Mr. MARKEY. And what did you do to address these anomalies at 

that time, in January 17th? 

Dr, CHEW. Well, at that time there was a request for additional 

data. Because at that time the number of actual cases that were 

reviewed, because of the volume of the randomization, the number 

of cases, individual patient records actually reviewed was 10. And 

I believe on November 29 of 2001, three by PPD. So clearly there 

needed to be more in-depth information obtained. And that was obtained by PPD on their 3-day monitoring on February 18th, 19th 

and the 21st, and that culminated in the teleconference on March 

the 4th to evaluate the potential for scientific misconduct and 

fraud. 

Mr. MARKEY. Now, on June 19, 2002, Ms. Jean Noon from PPD 

e-mailed Ms. Nadine Grethe of Aventis informing her we are still 

getting conflicting information from site S. They will tell us one 

thing, then the next time we call they tell us the opposite. This is 

particularly problematic when it comes to whether a subject was 

ever consented or not and what effect the drug subject took. Ms. 

Noon then continued the e-mail with specific examples of multiple 

treatment and informed consent problems. To this e-mail Ms. 

98 

Grethe replied, quote, at this point it is too late to change anything 

in the database. They filled it out with an informed consent date. 

And this is what we are going with. We are not changing this 

again. They screwed up. They will now have to take the blame. 

Also, if they keep changing their minds, then I really do not believe 

them now. 

Dr. Chew, what should Ms. Grethe have done in response to this 

e-mail? 

Dr. CHEW. Congressman, I saw that e-mail. It was difficult to 

know specifically which sites and which patients were discussed. 

With hindsight of course I think that more information could have 

been found out. I’m just inferring now that there probably were differences in documentation and inconsistencies in correspondence. 

And it’s my inference that they, the team, went with the best documentation they had. 

Mr. MARKEY. Is she still with Aventis? 

Dr. CHEW. Ms. Nadine Grethe is no longer with Aventis. 

Mr. MARKEY. And why did her separation occur? 

Dr. CHEW. I’m not quite clear, but I believe it was for other professional opportunities, to my knowledge. 

Mr. MARKEY. What has Aventis done to make sure that these 

kinds of errors do not recur in conjunction with future studies? 

Dr. CHEW. There has been a tremendous effort in looking at the 

lessons of 3014. Investigator selection, investigator training, investigator retraining, especially if they’re naive. One of the issues of 

this trial is it enrolled so fast. It was 24,000 patients in 3 months, 

one winter season, to catch the infections. This was reviewed with 

FDA. One winter season was felt to be adequate. One of the issues 

with such a large trial when it is recruiting so fast is the monitoring of these sites has to be on top of the situation. And when 

you look at the monitoring plan, which was designed for a typical 

controlled clinical trial, not a real world study, immediately I saw 

that there was a disconnect. Most of the patients had been randomized in the 3-month period before the monitoring could get on top 

of it. So one of the things we’ve done now is to control the rate of 

enrollment and put a cap on the enrollment. And you don’t go 

above that cap until you’ve been validated that you have good quality data that has been looked at internally. 

So the quality has to keep up with the quantity. That’s one of 

the key things. You see in this trial there was not a cap. There was 

a recommendation. Now there’s a cap. And so that we go lockstep, 

quantity and quality. So that’s one of the big things. Training, new 

SOPs and just a heightened awareness. Fraud is a very uncommon 

issue. 

Mr. MARKEY. Well, in light of your experience could this sort of 

situation happen again? 

Dr. CHEW. I will never say never, but I will say we will take all 

that’s humanly possible to minimize the chance of this happening 

again. I think fraud—we heard this morning fraud is something 

that does occur. But we’re going to minimize the scope, the scope, 

of this. And also not only fraud, but its serious GCP noncompliance. That’s not fraud, but that’s enough, that’s enough, in retrospect that I wished Aventis had called FDA to share their concerns 

and some more clarity on the threshold, and it may be difficult, the 

99 

threshold of contacting to not be burdensome to the agency, but to 

be responsive to problems. That’s an area that I think the industry 

would appreciate some guidance on. 

Mr. MARKEY. Well, I think you’re going to get all the guidance 

you need going forward, and this committee will provide that guidance for you and for other companies that will perhaps be in doubt 

as to what their responsibility is once potential fraud is identified 

to disclose it in a reasonable fashion so that the public health is 

protected. And I thank you, Mr. Chairman, for allowing me to participate. 

Mr. STUPAK. Thank you, Mr. Markey. Dr. Chew, let me ask you 

this. Do you think PPD did a good job for Aventis? 

Dr. CHEW. Looking back, I think PPD did a good job for Aventis. 

Mr. STUPAK. How about Copernicus, did they do a good job for 

Aventis? 

Dr. CHEW. It would be harder for me to say because the documentation of the exchange between Copernicus and Aventis at that 

time was not—I didn’t see an awful lot of documentation. 

Mr. STUPAK. Should Copernicus have let you know about the 89 

or 83 complaints they had? 

Dr. CHEW. Well, the memos to file, they came from Aventis. In 

other words, Aventis notified them. 

Mr. STUPAK. So you knew about it? 

Dr. CHEW. Those memos to file were sent to them. 

Mr. STUPAK. Did you expect the IRB, Copernicus here, then to 

notify the FDA? 

Dr. CHEW. Well, in hindsight I—looking back, I mean I would 

have expected Copernicus not to have, because it was the feeling 

when I—— 

Mr. STUPAK. Who does Copernicus work for, the patients or for 

you? 

Dr. CHEW. The patient’s safety is the IRB responsibility. So the 

ultimate responsibility, as it is with the sponsor, is patient safety. 

Mr. STUPAK. OK. The 24,000 people you’ve enrolled in this Ketek 

study, have you contacted them and said there may have been 

some problems with this study to see how they’re doing, because 

you have liver toxicity, you have an eye problem associated, you 

also have I think toxicity around the heart, right? Didn’t you have 

a cardiac toxicity here, too; three toxicities, eye, liver and heart, 

right? 

Dr. CHEW. Again, in this trial—— 

Mr. STUPAK. Did you contact the patients? 

Dr. CHEW. The patients were not contacted beyond the trial because half the trial was another drug for which you could compare. 

Mr. STUPAK. OK. Well, how about the 12,000 then on Ketek, did 

you contact them? 

Dr. CHEW. The 12,000 patients were filed before the trial, but 

they were not contacted to my knowledge after the trial was over, 

unless they had an ongoing adverse event. 

Mr. STUPAK. OK. How do you know if they’re having an ongoing 

adverse event if you don’t contact them? 

Dr. CHEW. The study protocol had a 5- or 10-day treatment, but 

then there was a 35-day or 27- to 35-day follow-up well beyond the 

existence of the drug in the body. 

100 

Mr. STUPAK. How many of the people, 12,000 people, who were 

supposed to receive Ketek, how many actually received it? 

Dr. CHEW. The details I would have to get back to you on. 

[The information was not submitted for inclusion in the record.] 

Mr. STUPAK. Give me an estimation, how many actually received 

it? 

Dr. CHEW. I’m guessing that those who were assigned more than, 

I’m just guessing, but that there would be 90 percent or more. 

Mr. STUPAK. How many of Dr. Kirkman’s patients, the 407 she 

had enrolled in her study, how many of them actually received 

Ketek, do you know? 

Dr. CHEW. I don’t know, and that’s because we didn’t talk to the 

patients. Aventis at that time did not speak with the patients to 

see if they actually had received the drug. 

Mr. STUPAK. OK. Go to the binder book. Ms. Price, if you could 

hand that down. Mr. Markey read parts of Exhibit No. 21 to you. 

That was the memo there from Nadine Grethe, who you said is no 

longer with Aventis. At this point it is too late to change anything 

databased. They filled it out with an informed consent date and 

that is what we’re going with. We are not changing this again. 

They screwed up. They will have to take blame. And also if they 

keep changing their minds then they really do not believe them 

now. 

You followed up, Aventis followed up with this e-mail, right? This 

was in June of 2002. You followed up with an audit, did you not, 

in Ketek and in your different sites? 

Dr. CHEW. I think the audits, I believe, went through this period. 

I have to get the precise date in which they stopped, but I think 

they did go through this period. 

[The information was not submitted for inclusion in the record.] 

Mr. STUPAK. OK. So after this e-mail you went through to do an 

audit to see what was going on with Ketek, right, with this study? 

Dr. CHEW. There may have been—this I think would have been 

near the end of the monitoring period. By monitoring versus auditing, I mean monitoring would be the PPD function. You would have 

to kind of get the actual dates. 

Mr. STUPAK. Let’s go to Exhibit No. 26 right there in front of you. 

Now, this is an audit by Aventis auditors, is it not? 

Dr. CHEW. Yes. It appears to be, yes. 

Mr. STUPAK. And the date of the original message is Tuesday, 

October 29, 2002, correct? 

Dr. CHEW. That’s right. 

Mr. STUPAK. So this is about 3 or 4 months after Exhibit No. 21, 

right, when you’re concerned about it? 

Dr. CHEW. That’s right. 

Mr. STUPAK. And what you did, you did an audit of the sites that 

had enrolled more than 100 subjects in this Ketek Study 3014, correct? 

Dr. CHEW. In this listing, yes. 

Mr. STUPAK. In every one of them, if you turn to the next page 

starting with Dr. Gardner, Dr. Anne Kirkman-Campbell, Dr. Lang, 

Dr. Shoemaker, Dr. Price, Dr. Tenscal, Dr. Stone, Dr. Blanchard, 

Dr. Glice, Dr. Resnick, they all had significant problems as to the 

101 

review of your own auditor, Aventis auditor, significant problems, 

correct? 

Dr. CHEW. Yes. 

Mr. STUPAK. And not just the informed consent, but significant 

problems that required corrective action this auditor said, right? 

Dr. CHEW. Yes, corrective action. 

Mr. STUPAK. Right. It said in every one of them significant issues 

that require corrective action. What corrective action did Aventis 

take? 

Dr. CHEW. Without commenting specifically on each site and 

each intervention, I believe that at the time you can see where the 

audit dates were. The audit dates were January, February and 

March. The enrollment had completed. The monitoring at the time 

and the auditing at that time was to document what was found. 

Mr. STUPAK. Significant problems were found. 

Dr. CHEW. What was found. And that the investigator was aware 

of this and documented it. These were monitoring visits that occurred. Normally monitoring visits are to help future patients, not 

only to fix the problem you have now, but for future patients. To 

my knowledge, probably most of the patients had already come and 

gone. 

Mr. STUPAK. Sure. But let’s get to the basis here. 

Dr. CHEW. Yes. 

Mr. STUPAK. Based on 21 you had a problem. In June of 2001 

you knew there was a problem based upon Exhibit No. 21, that 

there was serious problems here with your study. And you want to 

use this study to verify the safety of Ketek, Aventis does, right, 

that’s the reason for this study? 

Dr. CHEW. The request was to get additional safety information. 

Mr. STUPAK. Right. So you do this large study. You say you have 

to do it during the flu season so you enroll 24,000 people. You use 

these sites all around the country, 1,800 sites. 

Dr. CHEW. That’s right. 

Mr. STUPAK. And you audit 10 sites, right? Usually you do 10 

percent of your sites, do you not? Isn’t that the general standard? 

Dr. CHEW. I don’t know what the algorithm is, but it’s more than 

10. 

Mr. STUPAK. Right. It should have been about 180 sites, but you 

only did 10. Aventis went through and audited 10 sites, the largest 

sites, correct? 

Dr. CHEW. Well, I don’t agree that it would have been 180, but 

it would have been more than 10. They should have done more 

than 10, in my view. 

Mr. STUPAK. The point is you only audited 10 sites, 10 of the 

sites with the most patients in, correct? 

Dr. CHEW. They were the high enrolling sites, yeah. 

Mr. STUPAK. Correct, the high enrolling sites. So you did 10. You 

didn’t audit any other sites, they did just 19, right? 

Dr. CHEW. The monitoring was done of course more extensively, 

but the audit was on 10. 

Mr. STUPAK. Only 10 sites. Those 10 sites with the high enrollment patients, right, high enrollment patients in these sites, these 

are ones you audited. And this is October 29, 2002, your auditor 

at every one of the sites, not just Kirkman-Campbell, but every one 

102 

of the sites finds significant problems in which corrective action 

has to be taken, correct? 

Dr. CHEW. There were issues found that needed corrective action, 

correct. I think there are varying degrees of intensity. 

Mr. STUPAK. Go through if you want. Every one of them says significant issues where corrective action is required. Every one of 

them. Significant GCP issues identified during the monitoring. 

They find in the audit significant issues requiring corrective action. 

Dr. Lang, significant issues that require corrective action. Dr. 

Shoemaker, a significant issue that required corrective action. 

Dr. CHEW. I agree. 

Mr. STUPAK. So the whole basis of your safety study in your 

audit showed that you had significant issues that required corrective action, correct? 

Dr. CHEW. These were 10 sites that were audited. 

Mr. STUPAK. These are the only 10 you did, right? In fact you 

could ask the question, all the sites you monitored you found significant issues that required corrective action, isn’t that right? 

Dr. CHEW. Not all the sites monitored had significant GCPs that 

required action. 

Mr. STUPAK. Well, you just said that you only did 10 sites. 

Dr. CHEW. I’m talking about the monitoring. 

Mr. STUPAK. I’m not talking about the monitoring. Don’t confuse 

this here. We’re talking about the audit. 

Dr. CHEW. Of the audits, yes. 

Mr. STUPAK. Aventis only audited 10 sites in this big study and 

every one of them had significant issues that required corrective 

action, correct? 

Dr. CHEW. They had significant GCP issues that required corrective action, that’s correct. 

Mr. STUPAK. So how in good conscience could Aventis submit the 

study when every one of the audit sites there were significant problems to the FDA to show the safety of Ketek? 

Dr. CHEW. My answer to that, Congressman, is that to my 

knowledge these actions were not ignored, they were discovered 

and they were corrected and documented. Not all of them affect— 

to my knowledge, not all of them bore on the safety issue of Ketek. 

Mr. STUPAK. Well, really? Significant issues that require corrective action? The study is over. You only had this window, the flu 

season, as you said, to get it done. You can’t go back and replace 

that flu season, it’s over. You audited. You find the basis during 

this limited period of time you had have significant issues at every 

site. And that’s with the basis of the whole study. In every one of 

them you find significant—you didn’t find any clean ones. Every 

one of them were wrong. But yet you present that study to the 

FDA for safety of Ketek. How could you do that? Why would you 

do that? 

Dr. CHEW. It’s my belief that these problems were identified and 

documented by the audit and subsequently corrected and documented. 

Mr. STUPAK. How can you correct it? The flu season is done, the 

Ketek is over, you said they didn’t have any more time. Ketek is 

over. These patients aren’t getting it any more. And these are the 

103 

only patients you relied upon for the safety of the study that 

present to the FDA. How can you correct it? 

Dr. CHEW. The issues were documented and corrective action was 

taken in terms of documentation. You’re right, the patients had 

come and gone. 

Mr. STUPAK. Yeah. How do you document blood splitting? 

Dr. CHEW. I’m sorry? 

Mr. STUPAK. How do you correct blood splitting? You get blood, 

you attribute it to different patients, even though it’s not their 

blood to show that everything was fine for the safety of Ketek. How 

do you correct that? 

Dr. CHEW. To my knowledge there was no—in these cases there 

was no evidence of blood splitting. 

Mr. STUPAK. Dr. Kirkman-Campbell had blood splitting. 

Dr. CHEW. But Dr. Kirkman-Campbell had the suspicion of blood 

splitting. Both PPD and Aventis did statistical analyses that were 

not conclusive, that were not conclusive in terms of the blood splitting, to my knowledge. 

Mr. STUPAK. Ms. Price, did Copernicus check Dr. Kirkman-Campbell about blood splitting? 

Ms. PRICE. No, sir. 

Mr. STUPAK. No, you didn’t, did you? 

Ms. PRICE. Excuse me? 

Mr. STUPAK. Blood splitting where you use blood from different— 

you didn’t check that, did you? 

Ms. PRICE. No sir, that’s not our role. 

Mr. STUPAK. How about you, Dr. Eshelman? Did the PPD check 

for blood splitting? 

Mr. ESHELMAN. I believe that we turned up the suspicion of blood 

splitting. 

Mr. STUPAK. Did you go back and check it to verify it to make 

sure it didn’t have any effect—— 

Mr. ESHELMAN. Dr. Reynolds reviewed all of these cases, and I 

believe that Dr. Reynolds talked to someone at Aventis. I can’t 

swear to that, but I believe that is true. I do know that the issue 

of the possibility of blood splitting was discussed between the two 

companies. And I think, as I said in my prepared remarks, this was 

evaluated statistically and otherwise by Aventis at the time. And 

their investigation did not seem to indicate mathematically that 

there was a type of variability that would be associated with blood 

splitting. Dr. Reynolds looked at it some more after that. Whether 

or not he did a mathematical analysis I cannot remember frankly. 

Mr. STUPAK. So they didn’t do the blood splitting, they didn’t 

check it, so Aventis checked it and that was OK? 

Dr. CHEW. There is I believe an e-mail from PPD indicating they 

did analyze for blood splitting looking at the delta and comparing 

of other sites. As with the Aventis analysis there was a suspicion 

but no firm proof, to my knowledge, of blood splitting. 

Mr. STUPAK. OK. Let me ask you this. You hired Dr. KirkmanCampbell, right, Aventis? 

Dr. CHEW. To my knowledge, the investigator selection was the 

responsibility of PPD. 

Mr. STUPAK. Dr. Eshelman, did you hire Kirkman-Campbell 

then? 

104 

Mr. ESHELMAN. The answer to your question is I don’t know. My 

recollection is that the—— 

Mr. STUPAK. I love it. The main person and no one knows who 

hired her. It’s amazing. 

Mr. ESHELMAN. If you would let me finish. 

Mr. STUPAK. Yeah, sure. I’m trying to, but my disbelief is just 

overwhelming me. Go ahead. 

Mr. ESHELMAN. My recollection is that the identification and selection of investigators was a shared responsibility between Aventis 

and PPD. In other words, I believe that they had some investigator 

list. I believe that we had some investigator list. And that those 

were merged. And then subsequently the ones that came out of 

that as qualified were selected. So in the particular case of 

Kirkman-Campbell I can’t tell you where that name came from, I’m 

sorry. 

Mr. STUPAK. OK. PPD was hired by Aventis to monitor Study 

3014 and detect noncompliance, isn’t that correct, Mr. Chew? 

Dr. CHEW. They were hired to monitor the study and of course 

to transmit to Aventis the findings. 

Mr. STUPAK. Several of the PPD personnel involved in Study 

3014 informed the committee staff that they were reasonably sure 

that Kirkman-Campbell submitted fraudulent data to Aventis. Did 

PPD then have a duty to notify the FDA; in your estimation, did 

PPD have a duty to notify the FDA when they reached this conclusion? 

Dr. CHEW. I just have a personal opinion on that, because I don’t 

know if there is a legal requirement. I believe anybody, anyone at 

any time if they suspect a problem, should feel free to notify FDA. 

I don’t know if there is a legal answer to that. That would be my 

personal opinion. 

Mr. STUPAK. Dr. Eshelman sort of indicated that there is a contractual obligation that they could not do that. You disagree with 

that or—— 

Dr. CHEW. Well, I think that by contract there are usually—assignment who does what. But in most cases if there is a problem, 

you agree on who does what and you do it. That is the way I would 

do it. 

Mr. STUPAK. So did you require that—did Aventis require PPD 

not to report any problems? 

Dr. CHEW. I am not quite sure, but I think it is my recollection 

that Aventis had the regulatory liaison contact. Just to keep things 

clear, who was doing what. 

Mr. STUPAK. But as far as Aventis was concerned, Copernicus 

could notify the FDA, PPD could notify the FDA—— 

Dr. CHEW. Again, I am speaking individually. If there were an 

issue, I think what would happen—I am just hypothetically—is 

that Copernicus or PPD would discuss this, and there would be a 

resolution as to who does what. That has been my experience that 

usually there is consensus. 

Mr. STUPAK. How about Aventis? Did you ever notify the FDA 

that you had trouble with this Study 3014? Did you ever sit 

down—— 

Dr. CHEW. Yes, we did. Yes, we did. 

Mr. STUPAK. When was that? 

105 

Dr. CHEW. I believe in June of 2002, I believe, prior to the filing, 

when there were two sites who persistently refused to cooperate. 

Mr. STUPAK. June of 2002. But tab number 26 shows that’s October of 2002. So after—how about October, after your audit of October of 2002, did you notify the FDA of problems with the sites? 

Dr. CHEW. To my knowledge, the two that were notified did not 

cooperate. I am assuming, and would have to look individually, 

that these sites were probably cooperative in coming into documentary compliance. 

Mr. STUPAK. After your audit, tab number 26. 

Dr. CHEW. It could have been after the audit or the monitoring, 

because the monitoring was in parallel. 

Mr. STUPAK. OK. At any time after tab 26, October of 2002, did 

Aventis contact the FDA and tell them, We have trouble with this 

Study 3014 and it may be based on fraudulent activities? 

Dr. CHEW. To my knowledge, the team that was looking at this 

felt that they had addressed many of the issues of GCP noncompliance. And when the auditor came from FDA to look at Dr. 

Kirkman-Campbell’s site specifically over a 9-day period from October 15th to the 24th, the documentary evidence of that audit corroborated many of the same GCP violations that were found by the 

team. 

Mr. STUPAK. Great. But my question was did Aventis, after October of 2002, notify the FDA of problems? We are not just talking 

about Kirkman-Campbell. October of 2002 has nine other sites, and 

every one of them had significant issues that needed corrective action. Did Aventis notify the FDA of these other sites that had significant issues that needed corrective action? 

Dr. CHEW. To my knowledge—and I would have to review—I 

don’t think so. 

Mr. STUPAK. OK. Where does your responsibility come in, then, 

when you appear before the FDA and the FDA advisory committee, 

to tell the FDA that you have had significant problems with the 10 

sites—the only sites you audited, all 10 of them had significant 

problems that needed corrective action—when is it your responsibility to let the FDA know? 

Dr. CHEW. Are you talking about hypothetically or this specific 

trial? 

Mr. STUPAK. I am talking about Aventis here and on this Ketek. 

When did you have that responsibility? 

Dr. CHEW. Of course, we do things differently now with the new 

company. 

Mr. STUPAK. I know everyone does everything different now, 

but—— 

Dr. CHEW. But at that time, at that time it is my understanding 

the company reviewed these issues with the site, had documented 

these errors, again in retrospect, and in other words they had addressed the issues as best they could in a retrospective fashion. 

Mr. STUPAK. Dr. Chew—— 

Dr. CHEW. Yes. 

Mr. STUPAK. The answer is just that. Look. After October of 

2002, you did nothing to notify FDA of the problems with the integrity of Study 3014. Did Aventis? They did not, did they? 

Dr. CHEW. I believe Aventis felt that the trial had integrity. 

106 

Mr. STUPAK. That’s not what I asked. OK. You think this is—you 

believe this has integrity, this 3014 has integrity? 

Dr. CHEW. I am sorry, could you repeat that? I am sorry. 

Mr. STUPAK. Sure. After October 2002—— 

Dr. CHEW. Yes. 

Mr. STUPAK [continuing]. After your audit, 10 sites, every one of 

them has significant issues that need corrective action, you never 

notified the FDA of possible integrity issues with Study 3014. 

Dr. CHEW. The FDA had opened up a criminal investigation. 

Mr. STUPAK. That’s not what I asked. 

Dr. CHEW. But to my knowledge, there had been no notification, 

because it is my review of the record that these issues with these 

other sites had been addressed in terms of memos to file. An inadequate approach—— 

Mr. STUPAK. Memo to file from who, Aventis to Aventis? 

Dr. CHEW. The memos to file would usually be the investigator 

going to the file. 

Mr. STUPAK. In other words, your investigators going to your 

files? 

Dr. CHEW. No, this would be at the site. So that they could be 

audited and reviewed by auditors. The specific point being to have 

the documentation. 

Mr. STUPAK. They could be. But what is your responsibility here? 

October 2002, 10 sites, every one significant problems, need corrective action. Did you notify the FDA about that? That’s all I am asking you. 

Dr. CHEW. At that time, the answer, to my knowledge, is no. 

Mr. STUPAK. OK. So even though you submitted this study, you 

never told the FDA that of the 10 sites that were audited you had 

significant issues with? 

Dr. CHEW. It is my understanding that these issues had been addressed at the time they were documented at previous monitoring. 

Mr. STUPAK. Who addressed these issues? Aventis, right? 

Dr. CHEW. Typically, the PPD would identify these issues, report 

them to Aventis, and the site would be instructed to document 

what had happened. 

Mr. STUPAK. Sites were already closed. We have established that. 

That is already closed. 

Dr. CHEW. When it came to the monitoring, as usual in any trial 

when there is monitoring, the issues have to be fixed and corrected. 

The enrollment had stopped, but the sites may still have been in 

the process of regulatory and document assembly. So we have to 

separate out the enrollment of patients, which is 3 months, and the 

monitoring that went on for much longer, obviously. 

Mr. STUPAK. Why do you do an audit? 

Dr. CHEW. The audit is to generally look at processes to see if 

the processes have been fulfilled. 

Mr. STUPAK. And of these 10 audits, every one of them failed. 

Dr. CHEW. Of these high enrolling sites, there were significant 

issues requiring action. 

Mr. STUPAK. Isn’t an audit to help determine the integrity and 

the quality of the study you are doing? 

Dr. CHEW. There is more than auditing to do that, but auditing 

is part of it. 

107 

Mr. STUPAK. Correct. And you batted a big zero on that one, so 

there is a serious question about the quality of the report, then, is 

there not, of the study you are doing? 

Dr. CHEW. From my understanding, these issues were found and 

identified. It was not a blemish-free trial. These issues were identified after the patients had come through the trial. But it is my understanding—— 

Mr. STUPAK. What was your revenue, what was Aventis’s revenue from Ketek back in 2005? 

Dr. CHEW. I would have to find that out. 

Mr. STUPAK. 264 million sound right? 

Dr. CHEW. I would have to document that. 

Mr. STUPAK. You have any reason to dispute 264 million? 

Dr. CHEW. No, I just have no primary knowledge of that number. 

Mr. STUPAK. I see. A year ago the FDA finally removed bronchitis and sinusitis from the labeled indications for Ketek, leaving 

only pneumonia as an authorized use for the drug. Is that correct? 

Dr. CHEW. That’s correct. 

Mr. STUPAK. Is Sanofi-Aventis still detailing the drug to doctors? 

Dr. CHEW. To my knowledge, no, there is no promotion. 

Mr. STUPAK. OK. Your auditors were at Kirkman-Campbell’s site 

one week before the FDA investigator who told the congressional 

staff that Kirkman-Campbell’s site was the worst she had seen in 

25 years. How did your auditors miss the fraud there at KirkmanCampbell? 

Dr. CHEW. It was the auditors who identified, in January I think, 

17th, 18th, 2002, that there was a potential problem; additional 

monitoring needed to be done. That’s where PPD was sent on February 18th, 19th and 21st. There were additional visits April 1 

through 5. There were 165 calls to this site. There was extensive 

attention paid to this site. 

Mr. STUPAK. Right. And did you disclose all that to the FDA? 

Dr. CHEW. Well, no. The answer is no because the issues were 

addressed and documented for the file. And it is my knowledge that 

this was also documented by the 483 that was issued on October 

24th by the FDA auditor. 

Mr. STUPAK. I asked the other investigators, I guess it is only 

fair to ask you—let me find it here—the statute of limitations on 

the possibility of indicating Aventis for fraud in connection with 

Study 3014, when the investigators were kicking around the date, 

since the approval was, I believe, April 1st, 2004 for Ketek? 

Dr. CHEW. That’s correct. 

Mr. STUPAK. And if that approval is based upon fraud, fraudulent Study 3014, do you think Aventis is liable then for fraud? 

Dr. CHEW. Can I answer that by it’s my understanding that FDA 

did not rely on 3014 for its approval, having 14 clinical trials, also 

having the German registry, and at that time 4 million patients’ 

use. So it is my understanding that 3014 was not used. 

Mr. STUPAK. But Aventis, in submitting Study 3014 to the advisory panel, which I believe was on March 25th—not advisory, the 

advisory—— 

Dr. CHEW. September 15th and 16th, 2006. 

Mr. STUPAK. OK, January. Why did you present Study 3014 to 

show the efficacy and the safety—— 

108 

Dr. CHEW. Are you talking about the second advisory committee? 

Is that right? 2003? 

Mr. STUPAK. Yes. Yes. 

Dr. CHEW. Right. 

Mr. STUPAK. Why did you submit 3014, which showed the efficacy and the safety of Ketek, was it not, for bronchitis, for sinus, 

and for pneumonia, correct? 

Dr. CHEW. The primary was safety. Efficacy had been established 

according to the first advisory committee with the 14 pivotal trials 

of phase 3 and those three indications. 

Mr. STUPAK. OK. So you submitted for safety. Correct? 

Dr. CHEW. Yes. 

Mr. STUPAK. OK. And if there is fraud in that safety, would you 

then agree with us the statute of limitations run on possibly indicting Aventis for fraud in connection with the safety of Study 3014? 

Dr. CHEW. I can’t comment on this legal term. I am not competent to do that. But at the time of the submission, it is my review, that Aventis felt that this was a trial that was useful and 

that the issues of good clinical practice had been addressed. 

Mr. STUPAK. Useful. You said useful. But when you submitted, 

you thought that Study 3014 showed the safety of Ketek. 

Dr. CHEW. At that time—— 

Mr. STUPAK. Yes. 

Dr. CHEW [continuing]. It is my understanding that this was submitted as a useful response to the request of the first advisory committee for a large safety study. And that was done. 

Mr. STUPAK. And it was submitted for the verification of the safety of Ketek for these three problems: sinus, pneumonia, bronchitis. 

Dr. CHEW. It was to get additional information as part of other 

experiences, but it was to provide a large safety experience for 

Ketek in those three indications, compared to a commonly used antibiotic. 

Mr. STUPAK. Mr. Shimkus for questions. 

Mr. SHIMKUS. Thank you, Mr. Chairman. And I am not going to 

be that long. You have spent a lot of time. 

Mr. STUPAK. I have more questions. 

Mr. SHIMKUS. I am sure here they are waiting for them, too. 

I do want to follow up with what the Chairman mentioned, the 

10 sites out of 1,800 sites. You know, when we in any—I have got 

an engineering background to some extent, although I am a politician. And polling is an important aspect of our job and what we 

do. Of course we are having a lot of polling now with the Presidential race. There are legitimate polls and there are illegitimate 

polls, and it is based upon how really the science is conducted by 

the sample size, the randomness, and all the other aspects. 

Is there any such standard as to what is an acceptable universe 

of study on percentages when you have—this is for Dr. Chew— 

when you pull out 10 sites out of 1,800 sites? 

Dr. CHEW. It is my feeling—I am not a statistician—there should 

have been more sites audited. The pattern in this case, though, of 

the 10 sites that were audited, is that they were chosen because 

of their higher enrollment. And high enrollment, as you might suspect, is where people who might commit fraud, especially for monetary gain, may be concentrated. So it may not be truly a random 

109 

sample of the 1,800 sites; it is 10 out of 1,800, but it is the high 

enrolling sites. 

Mr. SHIMKUS. Yeah. If all those sites had problems, then what 

does it tell you about the process of choosing the 10 sites? 

Dr. CHEW. About choosing? Well, I think it is more than choosing. It is the training, and it has to be more in time monitoring. 

You can’t show up after the trial is over. So it is selection, training. 

These are all the things that are done now. And more in time monitoring. Putting a cap on enrollment. And you don’t go above that 

cap until you have had your data validated. 

Mr. SHIMKUS. If we have identified, obviously, a problem, let’s go 

back to the basic premise of the initial question again. A credible 

poll has to have a sample size over 300, has to be random, it has 

to go across the demographics of the particular area. You can’t 

weigh it to one side over another. How do we get a credible scientific sample, or is there a formula by which we would be deemed 

legitimate? 

Dr. CHEW. You are talking in general? 

Mr. SHIMKUS. Yeah. Because part of this is identifying this error. 

Dr. CHEW. Right. 

Mr. SHIMKUS. But also part of oversight is identifying this error 

so we can make sure these errors do not happen in the future. 

Dr. CHEW. Sure. 

Mr. SHIMKUS. So how do we make—how do we ensure that there 

is legitimate randomness and a sample size big enough that covers? 

I think most people would say 10—I guess the point is, a number 

of enrollees in a site may affect that, but still 10 out of 1,800 sites, 

I think just a casual observer would say, well, no wonder there’s 

problems. 

Dr. CHEW. I am not a statistician. I don’t think 10 is enough. 

This was not a random sample. This is where the high enrollers 

were. And I believe that the FDA also takes a similar approach, 

which is to go where the high enrollers are because—— 

Mr. SHIMKUS. Just because the FDA does something doesn’t—— 

Dr. CHEW. No, no, I am not saying. I mean that is where you are 

likely to find problems. It is not a random sample. I think a random sample, of course, would choose these sites randomly in terms 

of the demographics either by the type of doctor, the type of illness. 

It would probably have to be on a case-by-case basis and would 

have to be truly random, not skewed toward one end of the enrollment spectrum, because you may find the problems there but then 

attribute that to the whole sample. 

Mr. SHIMKUS. The other aspect, I was county treasurer at one 

time for 6 years. And one basic management principle is management by walking around, which means you walk around all your 

employees’ offices, you visit with them, you see them, you see what 

is on their desks, you come at different times. Visiting 10 sites out 

of 1,800 sites on a research isn’t really perceived—would be perceived as good management by walking around when you are talking about the health and welfare and the safety and the efficacy 

of drug testing. And so maybe there is an attempt or we need to 

be more specific on a formulary basis about where we have to be 

and in what numbers and in what percentages and the like. 

110 

Dr. CHEW. Well, you know, the auditing is to be different from 

the monitoring. And I did want to clarify that. Monitoring of these 

1,800 sites was that—I believe 99.6 percent, a very high number 

of sites that recruited 15 or more were visited physically. And I believe that—and that accounts for 80 percent of the patients. 

There were also weekly phone calls to all the sites, 26,000 phone 

calls in this trial. And apart from the weekly status, there were additional phone calls, of course, as the need arose, to over 90,000 

phone calls. And overall, I believe approximately 58 percent of the 

sites, more than 900 during the study, received on-site visits. 

Now, those are the statistics. But the issue was the trial recruited so fast that I believe most of the visits occurred after the 

randomization and treatment period had gone through. So monitoring ideally should be not only an educational training repair 

process for patients who have been through, but for patients yet to 

come. That did not occur in 3014, and that is what has been 

changed for the large trials that Sanofi-Aventis is doing now—for 

all trials that Sanofi-Aventis is doing now. 

Mr. SHIMKUS. If these 10 were the top sites, if they were the top 

sites you could almost conclude that most sites had problems, then. 

Dr. CHEW. Well, I think it is hard to say that, because it is the 

expectation that the high enrolling sites, if there is monetary reward as the goal for the fast enrollment and the high enrollment, 

may concentrate or be where the issues may concentrate. It is not 

a random sample. It is everything but a random sample. It is the 

highest enrollers out of 1,800. 

Mr. SHIMKUS. When you get this information, what is the conclusion that you draw about the integrity of the whole thing? What 

would be the conclusion then? 

Dr. CHEW. As I said, I think it is investigator selection, training, 

retraining, monitoring. And you got to get on top, you got to get 

on top—— 

Mr. SHIMKUS. The conclusion would be the data integrity was not 

solid. 

Dr. CHEW. The data integrity was looked at not only by what was 

found, but what was done about it. Now, as we said, what was 

done about it was to document in retrospect, because in most cases 

the monitoring occurred after the thing. So that if you had a high 

enrolling site, it is likely that you would not have gotten out there 

to stem the bad practice. So when you got there it would be documenting with memos to file. Not adequate, very helpful, but in this 

case not adequate because it was retrospective. 

Mr. SHIMKUS. Dr. Eshelman, I saw you nodding or showing some 

signs along this line of questioning. Is there something you want 

to add? What about data integrity? And what conclusions should 

have been drawn? 

Mr. ESHELMAN. No, sir, I didn’t have anything to add on that 

particular issue. As it goes to data integrity. I think that is a caseby-case basis and determination made by the sponsor of the trial. 

I spent some time in big pharma prior to my CRO experience, so 

I am familiar with what goes on there as well, what the requirements are, what the standards are and so forth. And, you know, 

this case notwithstanding, it has always been my experience over 

the years that the sponsors, the CROs, everybody, is after data inVerDate Nov 24 2008 14:23 Apr 22, 2009 Jkt 037690 PO 00000 Frm 00114 Fmt 6633 Sfmt 6633 C:\DOCUMENTS AND SETTINGS\CWELLS1\110-87 SCOM1 PsN: JIMC
111 

tegrity. We know what we are here for. And the down side of not 

doing that is so steep that only a fool would go there, in my view. 

Mr. SHIMKUS. I would like to follow up with you on the monitoring plan for this Study 3014. Was there dedicated sufficient resources for the implementing of the program? 

Mr. ESHELMAN. By whom? 

Mr. SHIMKUS. By you. 

Mr. ESHELMAN. By PPD? 

Mr. SHIMKUS. Yeah. 

Mr. ESHELMAN. Actually, I was on the phone over the weekend 

with the person who was the project coordinator at PPD for this 

trial, and I put that very question to her. I said, Were you adequately resourced? And she said, yes, at the beginning of the trial 

that she felt like she was adequately resourced. We were resourced 

to the contractual requirements and so forth. 

But to Dr. Chew’s point, I think certainly PPD, and it sounds 

like perhaps Aventis as well, underestimated the workload that 

was suddenly going to appear here because of the 24,000 patients, 

how quickly they were randomized. And I think more importantly, 

perhaps in this instance, as it has to do with short-term therapy 

on an antibiotic, by the time some of the problems are identified 

and so forth, the therapy is so short that you really don’t have time 

to make some corrections in real time. And therefore, you are doing 

it after the fact. This was also targeted monitoring. 

So by definition we were not going to look at every site in every 

case and so forth as you might do in a standard phase 3 trial. So, 

you know, in retrospect, in some respects we were almost set up 

for some of these problems. 

Mr. SHIMKUS. And finally, on the resource question, did Aventis 

give you all the tools you needed to do your part? 

Mr. ESHELMAN. Yes. I think so. 

Mr. SHIMKUS. And let me just add—I am going to end with this, 

Mr. Chairman—back to Dr. Chew. I would like to discuss the research and development of antibiotics. Since Ketek’s approval, how 

many antibiotics has Sanofi-Aventis developed or begun to develop? 

Dr. CHEW. None. There may be something very early, but there 

is nothing in the late stage. 

Mr. SHIMKUS. Has the company’s experience with this study, especially 3014 and the events thereafter, caused it to reduce its research and development efforts and develop new antibiotics? 

Dr. CHEW. Well, I don’t want to speak about the antibiotic program in general. Let me say that R&D has always been challenging. We realize that this is a heavily regulated industry, as it 

should be. I only got involved in this personally, because of my own 

commitment as a physician, to go beyond individual patient care to 

broader patient care. So we recognize the hurdles are high, and we 

have not reduced R&D development in general. 

Mr. SHIMKUS. Thank you, Mr. Chairman. 

Mr. STUPAK. Thank you, Mr. Shimkus. Thanks for getting here. 

I know it has been a hassle today. 

Dr. Eshelman, if I say that right, adequately resourced; PPD was paid close to $30 million to do their work here, were they not? 

Mr. ESHELMAN. My recollection is the payment for direct costs 

was somewhere around 20, and the pass-through costs, in other 

112 

words the payments to the physicians, were somewhere around 8. 

So ours was 20, investigators 8. That is my recollection. 

Mr. STUPAK. OK. So $20 million to do it. What was your response—I asked Dr. Chew, it is probably better to ask you—what 

was your responsibility as the contract research organization to report the sites to the IRB when there was suspicion of fraud or 

other problems with this study? 

Mr. ESHELMAN. I believe we have such responsibility. And it 

sounds like, from the testimony of Ms. Price, that in fact a lot of 

that reporting did occur. 

Mr. STUPAK. OK. Nothing would have stopped PPD from alerting 

Copernicus, correct? 

Mr. ESHELMAN. No, sir. I am not aware of anything. 

Mr. STUPAK. OK. Did you notify Copernicus of the irregularities 

and possible forgery found by PPD at the Kirkman-Campbell site? 

Mr. ESHELMAN. I assume that we did. And it certainly sounds 

like there were a number of memos and so forth. I can’t comment 

factually on exactly what we communicated to Copernicus at any 

given time on the Kirkman-Campbell site, but I assume that this 

went on. 

Mr. STUPAK. Well, Ms. Cisneros worked for you, right? 

Mr. ESHELMAN. Yes. 

Mr. STUPAK. Made the first telephone call. And I think Ms. Price 

said 83 other complaints came from the Kirkman-Campbell site 

and other sites. Did you feel compelled, then, to notify Aventis 

about all these complaints? 

Mr. ESHELMAN. Yes, sir. 

Mr. STUPAK. OK. How about the FDA? Did you feel compelled to 

tell the FDA? 

Mr. ESHELMAN. No, sir, not in this case, because of the way the 

contract read, number one. And number two, there was some debate over whether or not this was to the level of fraud. I think the 

issue of data integrity that goes along with how you present data 

to the FDA or otherwise is a determination that has to be made 

by the sponsor. 

Mr. STUPAK. How can you say—in fact, Dr. Chew said the same 

thing—didn’t know if it went to the level of fraud, when the complaint said errors on just about every informed consent, date modifications, initials different from signature, study coordinator entering date for subjects and principal investigator, blatantly forged 

signature on informed consent, medical records are very limited, 

use of different color ink on medical charts, overwrites, crossouts, 

inserts of diagnosis in different color ink, routine failure to give 

pregnancy tests to women of childbearing years, study investigator 

and coordinator unaware of the definitions of serious adverse 

events, no adverse events for the first 300 patients enrolled with 

drugs known to have adverse events, lab results indicating blood 

splitting, lack of proper diagnosis for study eligibility, husbands 

and wives being enrolled together, large number of patients randomized in the interactive voice response system in a short increment of time when the office was closed. I mean, how would that 

not indicate fraud? 

Mr. ESHELMAN. If I could cut to the chase here. 

Mr. STUPAK. Yeah, please, I wish someone would. 

113 

Mr. ESHELMAN. Had I known in detail at the time what was 

going on, I would have picked up the phone. 

Mr. STUPAK. Whose responsibility is it? I mean we are hearing 

all these reports of all this stuff going on. 

Mr. ESHELMAN. It is mine. It is my responsibility. 

Mr. STUPAK. OK. 

Mr. ESHELMAN. In fact, I did not have all the facts at my disposal at that time. Had I known what I know now, in retrospect 

I would have picked up the phone and I would have called—Dr. 

Chew wasn’t there at the time, I don’t think—but I would have 

called someone at Aventis at a high level of authority and expressed my concerns about this. And I believe that if that had occurred there may have been a different response out of Aventis. 

Mr. STUPAK. You know Robert McCormick? 

Mr. ESHELMAN. Sure. 

Mr. STUPAK. Isn’t he your Vice President of Quality Management 

Systems? 

Mr. ESHELMAN. Yes. 

Mr. STUPAK. He didn’t talk to you about this? About all the problems? 

Mr. ESHELMAN. Not in detail about the Kirkman-Campbell site 

at the time. 

Mr. STUPAK. Not just Kirkman-Campbell. Any of the problems 

with the—— 

Mr. ESHELMAN. Certainly with Dr. McCloud. 

Mr. STUPAK. OK. So you knew about it then? 

Mr. ESHELMAN. About Dr. McCloud? Yes, I did. 

Mr. STUPAK. And about the other problems with Study 3014. 

Mr. ESHELMAN. No, sir, I did not know the magnitude of those 

problems. 

Mr. STUPAK. So if Mr. McCormick said he informed you, that 

wouldn’t be right? 

Mr. ESHELMAN. Informed me about what? 

Mr. STUPAK. About the problems at Kirkman-Campbell and all 

the other issues involving this study, since you were the CEO of 

PPD. 

Mr. ESHELMAN. No, at the time, I don’t think that’s correct. I 

think subsequent to that it certainly is. It certainly is correct with 

respect to Dr. McCloud. He informed both myself and Dr. Covington. Mr. McCormick, Dr. Covington and myself were in total 

agreement about how the situation should be handled at Dr. 

McCloud’s site. And in fact, we made a no-name call to the FDA 

asking for guidance on that issue, and we never—— 

Mr. STUPAK. Just on McCloud. That’s the only one you 

talked—— 

Mr. ESHELMAN. Yes, sir. And we never got a response. 

Mr. STUPAK. So when McCormick says, tells our staff that it is 

your policy, PPD’s policy, to communicate significant complaints 

issues to you as CEO and that you are personally made aware of 

the large-scale irregularities and noncompliance of Dr. KirkmanCampbell, that is not true? 

Mr. ESHELMAN. The policy is certainly correct. 

Mr. STUPAK. OK. 

114 

Mr. ESHELMAN. It is not my recollection that I knew in detail at 

the time about Kirkman-Campbell, nor is it my recollection that I 

understood and appreciated the magnitude of the overall issue. 

Mr. STUPAK. Did PPD or anyone on your staff, did they recommend that Aventis call the FDA on these irregularities? Did you 

advocate—anyone from your company advocate to Aventis that 

they call the FDA on the irregularities on this study? 

Mr. ESHELMAN. I don’t know the answer to that. 

Mr. STUPAK. OK. Take a look at Exhibit No. 21. It is the one that 

Mr. Markey had asked about. 

Your employee, PPD’s employee, is notifying the Aventis study 

manager, who is no longer with Aventis, that she is receiving conflicting information from sites, including subjects who were never 

receiving—who never signed informed consents, and subjects who 

were treated with a different drug than that indicated in the existing database. 

And the Aventis study manager says, well, we can’t unlock the 

database. So is it ever acceptable to run with the data when you 

are unsure if the subject signed the consent form or if the data integrity issues that are listed here remained with the study? 

Mr. ESHELMAN. I think generally all of us in this business try to 

have a pristine database before we lock. So in other words, all of 

the outstanding queries have been answered and this and that and 

the other. If, however, you stumble across something post-lock that 

indicates that, in fact, your procedure was not robust, then generally speaking you unlock the database and you make whatever 

the corrections are. 

Mr. STUPAK. But that didn’t happen here. Did anyone unlock the 

database? 

Mr. ESHELMAN. I don’t know. I am sorry, I don’t know. 

Mr. STUPAK. Shouldn’t this e-mail have sent a red flag to your 

company that Aventis was not acting in good faith? 

Mr. ESHELMAN. I don’t know. I mean I am just not qualified to 

say. I don’t know—I don’t have any idea what was going on at 

Aventis. 

Mr. STUPAK. OK. But this is your employee, right? 

Mr. ESHELMAN. Yes. 

Mr. STUPAK. Who wrote this? 

Mr. ESHELMAN. Yes, sir. 

Mr. STUPAK. Shouldn’t you have done something about it, PPD? 

You have people that were allegedly in here, but they have no informed consent. This questions the integrity of the study. 

Mr. ESHELMAN. It is not our responsibility to dictate to a client 

what they do or do not put into a submission, nor is it our responsibility generally to dictate to them how they do their analyses. 

Now sometimes, as you know, there will be two sets of analyses. 

There will be an intent to treat that has everybody that ever received the drug, no matter what. OK. And then there will be what 

we would call a primary set of efficacy and safety data on—— 

Mr. STUPAK. And this would deal with the primary set of efficacy 

and safety with this drug, are we not? That was the purpose of this 

study. 

Mr. ESHELMAN. Ordinarily, that’s the set of data upon which—— 

115 

Mr. STUPAK. This study right here. It is safety, right? Wasn’t it 

the main purpose for the study? 

Mr. ESHELMAN. Yes, sir. 

Mr. STUPAK. OK. 

Mr. ESHELMAN. But the primary database, the one that you 

think is clean, would be the one that ordinarily I think a regulatory 

body would rely upon if they were going to rely upon the study. 

And it is my understanding they didn’t even rely on this study. 

Mr. STUPAK. So what are you saying, you keep two sets of books, 

you give the FDA the one that’s the best for your drug? 

Mr. ESHELMAN. No, sir. You give them both the analyses. This 

is standard practice. Because we want to be sure that we fully report everybody that got the drug for safety purposes. For that very 

reason, you report all of them. 

Mr. STUPAK. But if people in your study did not receive the drug 

and there is no informed consent, doesn’t that question the integrity of the study? 

Mr. ESHELMAN. Yes, sir, and therefore there might be more than 

one analysis done. 

Mr. STUPAK. And therefore shouldn’t PPD have done something 

about it, then, since your own employees questioned the integrity 

of the study? 

Mr. ESHELMAN. I don’t know what we would have done. We 

weren’t responsible for the submission. 

Mr. STUPAK. What is your responsibility then? 

Mr. ESHELMAN. Our responsibility was to monitor and to report 

to the sponsor. 

Mr. STUPAK. So outside that, you have no obligation to report to 

the FDA or anything else that there is some question? 

Mr. ESHELMAN. Not in terms of what was sent in a submission. 

Number one, we would have no way of knowing that. 

Mr. STUPAK. And if you think there’s questions about the integrity of data that’s going to be submitted to the FDA for drug safety, 

you have no responsibility to contact the FDA and say, Hey, take 

a closer look at this? I guess it’s more an ethical question. 

Mr. ESHELMAN. Obviously, if we were in a situation where we 

thought a sponsor was doing something egregious and they wanted 

us to be party to that, that would not happen. 

Mr. STUPAK. OK. I am not asking to be a party, but if you have 

knowledge that could go to the question of veracity of the study, 

that goes to the safety of a drug, do you have a responsibility then? 

Mr. ESHELMAN. But it wasn’t our determination to make, Mr. 

Chairman. 

Mr. STUPAK. By choice or by contractual obligation? 

Mr. ESHELMAN. I think by contractual obligation. I mean we just 

weren’t assigned that responsibility. 

Mr. STUPAK. How about company ethics then? Your first bullet 

in PPD’s mission statement says, as it says on your Web site: We 

will work with pride and unwavering integrity to help our clients 

accelerate delivery of safe and effective therapeutics to patients. 

In this case do you think you lived up to that mission statement? 

Don’t you think you had a responsibility for safe and effective 

therapeutics to patients? 

116 

Mr. ESHELMAN. I think under the conditions, we absolutely did 

our job in trying to identify departures from GCP, and data integrity issues, and, to some extent, fraud. I think Aventis did so as 

well with all of their checks and their audits and so forth and so 

on. To me, the issue of what did or did not get into a submission 

is—it is related, but it is a different issue. 

Mr. STUPAK. Well, I guess it is just not me thinking this. If I may 

go to Barron’s newspaper on November 12th, 2007, it reported that 

PPD, unlike many CROs, is willing to take a stake in some drugs 

being tested in exchange for free or cut-price monitoring service. 

Does that put you in a dangerous conflict-of-interest position? That 

is, you are essentially monitoring a drug in which you have a financial interest? 

Mr. ESHELMAN. Well, first of all, I don’t agree with all of that 

statement in Barron’s. We don’t do anything in exchange for cutrate monitoring. I don’t know what that means. 

But in terms of monitoring studies where we have a financial interest in the drug, I really don’t see how that is different from any 

sponsor monitoring studies because, you know, the drug came out 

of their research. So I don’t see how that is any different. 

Mr. STUPAK. But don’t you have the—isn’t PPD’s duty, one other 

duty in this and in 3014 was to train and select qualified investigators for the study? 

Mr. ESHELMAN. Certainly to select. We were not responsible for 

the training. That was another third-party vendor. 

Mr. STUPAK. OK. OK. Were you familiar with the Barron’s newspaper report, ‘‘The Very Pictures of Health,’’ by Jay Palmer, dated 

November 12th, 2007, in which they mentioned PPD, unlike other 

CROs, take a financial interest—— 

Mr. ESHELMAN. I can’t say that I was, because I might have 

called them up and taken exception to their statement. 

Mr. STUPAK. OK. I have nothing further. Mr. Shimkus, anything 

further? 

Mr. SHIMKUS. No, I don’t. 

Mr. STUPAK. OK. Then we will excuse this panel. Thank you all 

for coming today. That concludes all the questioning. I want to 

thank all the witnesses for coming here today, and for their testimony and their information they provided us. 

I would note that I am troubled by a number of the answers we 

have heard today. And accordingly, we will be considering referral 

of some of the materials to the FDA and to the Department of Justice. I don’t think it is just this panel. I think it was all the panels. 

We had troubles with these witnesses. Overall, I thought it was a 

good hearing, but many of us here are very troubled at what we 

heard today. 

So with that, I will ask for unanimous consent that the record 

remain open for 30 days for additional questions for the record. 

Without objection, the record will remain open. 

I ask unanimous consent that the contents of our document binder be entered into the record. Without objection, documents will be 

entered into the record. 

That concludes our hearing. And, without objection, this meeting 

of the subcommittee is adjourned. 

[Whereupon, at 3:39 p.m., the subcommittee was adjourned.] 

117 

[Material submitted for inclusion in the record follows:] 

118 


48587.001
119 


48587.002
120 


48587.003
121 


48587.004
122 


48587.005
123 


48587.006
124 


48587.007
125 


48587.008
126 


48587.009
127 


48587.010
128 


48587.011
129 


48587.012
130 


48587.013
131 


48587.014
132 


48587.015
133 


48587.016
134 


48587.017
135 


48587.018
136 


48587.019
137 


48587.020
138 


48587.021
139 


48587.022
140 


48587.023
141 


48587.024
142 


48587.025
143 


48587.026
144 


48587.027
145 


48587.028
146 


48587.029
147 


48587.030
148 


48587.031
149 


48587.032
150 


48587.033
151 


48587.034
152 


48587.035
153 


48587.036
154 


48587.037
155 


48587.038
156 


48587.039
157 


48587.040
158 


48587.041
159 


48587.042
160 


48587.064
161 


48587.065
162 


48587.066
163 


48587.067
164 


48587.068
165 


48587.069
166 


48587.070
167 


48587.071
168 


48587.072
169 


48587.073
170 


48587.074
171 


48587.075
172 


48587.076
173 


48587.077
174 


48587.078
175 


48587.079
176 


48587.080
177 


48587.081
178 


48587.082
179 


48587.083
180 


48587.084
181 


48587.085
182 


48587.086
183 


48587.087
184 


48587.088
185 


48587.089
186 


48587.090
187 

Æ 


48587.091