United States Government Accountability Office

GAO Testimony 

Before the Subcommittee on Health, 

Committee on Energy and Commerce, 

House of Representatives 

DRUG SAFETY

Further Actions Needed to 

Improve FDA’s Postmarket 

Decision-making Process 

Statement of Marcia Crosse 

Director, Health Care 

For Release on Delivery

Expected at 10:00 a.m. EDT 

May 9, 2007

 

GAO-07-856T 
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

May 9, 2007

DRUG SAFETY

Further Actions Needed to Improve FDA’s 

Highlights of GAO-07-856T, a testimony Postmarket Decision-making Process 

before the Subcommittee on Health, 

Committee on Energy and Commerce, 

House of Representatives

In 2004, several high-profile drug

safety cases raised concerns about

the Food and Drug

Administration’s (FDA) ability to 

manage postmarket drug safety 

issues. In some cases there were 

disagreements within FDA about 

how to address these issues. 

GAO was asked to testify on FDA’s 

oversight of drug safety. This 

testimony is based on Drug Safety: 

Improvement Needed in FDA’s 

Postmarket Decision-making and 

Oversight Process, GAO-06-402

(Mar. 31, 2006). The report focused

on the complex interaction

between two offices within FDA 

that are involved in postmarket 

drug safety activities: the Office of 

New Drugs (OND), and the Office

of Drug Safety (ODS). OND’s 

primary responsibility is to review

new drug applications, but it is also

involved in monitoring the safety of 

marketed drugs. ODS is focused 

primarily on postmarket drug 

safety issues. ODS is now called 

the Office of Surveillance and 

Epidemiology. 

For its report, GAO reviewed FDA 

policies, interviewed FDA staff, and 

conducted case studies of four

drugs with safety issues: Arava,

Baycol, Bextra, and Propulsid. To

gather information on FDA’s 

initiatives since March 2006 to

improve its decision-making

process for this testimony, GAO

interviewed FDA officials in

February and March 2007, and 

received updated information from

FDA in May 2007. 

In its March 2006 report, GAO found that FDA lacked clear and effective 

processes for making decisions about, and providing management oversight 

of, postmarket drug safety issues. There was a lack of clarity about how 

decisions were made and about organizational roles, insufficient oversight 

by management, and data constraints. GAO observed that there was a lack of 

criteria for determining what safety actions to take and when to take them. 

Insufficient communication between ODS and OND hindered the decisionmaking process. ODS management did not systematically track information 

about ongoing postmarket safety issues, including the recommendations that 

ODS staff made for safety actions. GAO also found that FDA faced data 

constraints that contributed to the difficulty in making postmarket safety 

decisions. GAO found that FDA’s access to data was constrained by both its 

limited authority to require drug sponsors to conduct postmarket studies 

and its limited resources for acquiring data from other external sources. 

During the course of GAO’s work for its March 2006 report, FDA began a 

variety of initiatives to improve its postmarket drug safety decision-making 

process, including the establishment of the Drug Safety Oversight Board. 

FDA also commissioned the Institute of Medicine to examine the drug safety

system, including FDA’s oversight of postmarket drug safety. GAO 

recommended in its March 2006 report that FDA take four steps to improve 

its decision-making process for postmarket safety. GAO recommended that 

FDA revise and implement its draft policy on the decision-making process 

for major postmarket safety actions, improve its process to resolve 

disagreements over safety decisions, clarify ODS’s role in scientific advisory 

committees, and systematically track postmarket drug safety issues. FDA 

has initiatives underway and under consideration and that, if implemented, 

could address three of GAO’s four recommendations. In the 2006 report 

GAO also suggested that Congress consider expanding FDA’s authority to 

require drug sponsors to conduct postmarket studies, as needed, to collect 

additional data on drug safety concerns. 

www.gao.gov/cgi-bin/getrpt?GAO-07-856T.

To view the full product, including the scope 

and methodology, click on the link above. 

For more information, contact Marcia Crosse, 

(202) 512-7119, crossem@gao.gov. 
Mr. Chairman and Members of the Subcommittee, 

I am pleased to be here today as you examine the safety of our nation’s 

drug supply. In 2004, several high-profile drug safety cases raised concerns 

about the Food and Drug Administration’s (FDA) ability to manage 

postmarket drug safety issues. Those cases showed that there were 

disagreements and potential delays within FDA about how to address 

serious safety problems. My remarks today are based on GAO’s March 

2006 report on FDA’s postmarket decision-making process (Drug Safety:

Improvement Needed in FDA’s Postmarket Decision-making and 

Oversight Process, GAO-06-402). I will also discuss a number of FDA’s 

initiatives to improve its decision-making process, including some that 

respond to the recommendations we made in that report.1

In carrying out the work for our report between December 2004 and 

March 2006, we focused on two offices within FDA’s Center for Drug 

Evaluation and Research (CDER) that are involved in postmarket drug 

safety activities: the Office of New Drugs (OND) and the Office of Drug 

Safety (ODS).2

 While there is some overlap in the activities of OND and 

ODS, they have different organizational characteristics and perspectives 

on postmarket drug safety. OND is involved in postmarket drug safety 

activities as one aspect of its larger responsibility to review new drug 

applications, and it has the ultimate responsibility to take regulatory 

action concerning the postmarket safety of drugs. ODS is primarily 

focused on postmarket drug safety, which includes the review of reports 

of adverse reactions to drugs. ODS operates primarily in a consultant 

capacity to OND and does not have any independent decision-making 

responsibility. 

For our report, we interviewed ODS, OND, and other CDER managers and

staff, as well as drug safety experts from outside FDA. We also analyzed

documents describing internal FDA policies and procedures. In order to 

obtain an in-depth understanding of FDA’s policies and procedures, we 

conducted case studies of four drugs—Arava, Baycol, Bextra, and 

 1

The report is available online at www.gao.gov/cgi-bin/getrpt?GAO-06-402. See Related 

GAO Products at the end of this statement for other GAO reports about FDA’s oversight of

prescription drugs.

2

ODS was renamed the Office of Surveillance and Epidemiology in May 2006. For the

purposes of this testimony, we are referring to this office by its former name. 

Page 1 GAO-07-856T
Propulsid—that help to illustrate the decision-making process.3

 Each of 

these drugs presented significant postmarket safety issues that FDA acted

upon in recent years, and they reflect differences in the type of adverse 

event or potential safety problem associated with each drug, the safety 

actions taken, and the OND and ODS staff involved. To follow up with 

FDA about its responses to our recommendations and its initiatives to 

improve its postmarket safety decision-making process, we interviewed 

four FDA managers, including CDER’s Associate Director for Safety Policy

and Communication, in February and March 2007, and received updated

information from FDA in May 2007. We did not evaluate the effectiveness 

of FDA’s efforts to respond to our recommendations. All of our work was 

conducted in accordance with generally accepted government auditing 

standards. 

In summary, we found that FDA lacked a clear and effective process for 

making decisions about, and providing management oversight of, 

postmarket drug safety issues. There was a lack of clarity about how 

decisions were made and about organizational roles, insufficient oversight 

by management, and data constraints. We observed that there was a lack 

of criteria for determining what safety actions to take and when to take

them, which likely contributed to disagreements over decisions about 

postmarket safety. Insufficient communication between ODS and OND’s 

divisions was an ongoing concern and hindered the decision-making 

process. For example, ODS did not always know how OND had responded 

to ODS’s safety analyses and recommendations. ODS management did not 

systematically track information about the recommendations its staff 

made and OND’s response. This limited the ability of ODS management to

provide effective oversight so that FDA could ensure that safety concerns

were addressed and resolved in a timely manner. FDA has faced data 

constraints that contributed to the difficulty in making postmarket safety 

decisions. In the absence of specific authority to require drug sponsors to 

conduct postmarket studies, FDA has often relied on drug sponsors 

voluntarily agreeing to conduct these studies. However, these studies have 

not consistently been completed. FDA has also had limited available 

resources to obtain data from outside sources. 

 3

FDA approved Arava to treat arthritis; Baycol to treat high cholesterol; Propulsid to treat

nighttime heartburn; and Bextra to relieve pain. Baycol, Bextra, and Propulsid have since

been withdrawn from the market (in August 2001, April 2005, and March 2000, 

respectively), and the warnings on Arava’s label were strengthened. 

Page 2 GAO-07-856T
FDA has undertaken a variety of initiatives to improve its postmarket drug 

safety decision-making process. Prior to the completion of our report in 

March 2006, FDA commissioned the Institute of Medicine (IOM) to 

examine the drug safety system, including FDA’s oversight of postmarket 

drug safety. FDA also established the Drug Safety Oversight Board in 

CDER and made other internal changes. Since March 2006, FDA has 

continued to address its oversight and decision-making shortcomings. In 

January 2007, FDA issued a detailed response to IOM’s recommendations. 

In our 2006 report, we recommended that FDA revise and implement its 

draft policy on the decision-making process for major postmarket safety 

actions, improve its process to resolve disagreements over safety 

decisions, clarify ODS’s role in scientific advisory committees, and 

systematically track postmarket drug safety issues. FDA has since begun 

to implement initiatives that we believe could address the goals of three of 

the four recommendations in our 2006 report. FDA has made revisions to, 

but not finalized, its draft policy on major postmarket drug safety 

decisions. FDA has not improved its process to resolve disagreements 

over safety decisions, and the agency is developing but has not finalized 

guidance to clarify ODS’s role in scientific advisory committees. FDA is in 

the process of implementing a tracking system. 

Because no drug is absolutely safe, FDA approves a drug for marketing 

when the agency judges that its known benefits outweigh its known risks. 

After a drug is on the market, FDA continues to assess its risks and 

benefits. FDA reviews reports of adverse drug reactions (adverse events)4

related to the drug and information from clinical studies about the drug 

that are conducted by the drug’s sponsor. FDA also reviews adverse events

from studies that follow the use of drugs in ongoing medical care 

(observational studies)5

 that are carried out by the drug’s sponsor, FDA, or 

other researchers. If FDA has information that a drug on the market may 

pose a significant health risk to consumers, it weighs the effect of the 

adverse events against the benefit of the drug to determine what actions, if 

any, are warranted. 

Background 

 4

Adverse event is the term used by FDA to refer to any untoward medical event associated 

with the use of a drug in humans. 

5

Observational studies can provide information about the association between certain drug 

exposures and adverse events. In observational studies, the investigator does not control 

the therapy, but observes and evaluates ongoing medical care. In contrast, in clinical trials 

the investigator controls the therapy to be received by participants and can test for causal 

relationships. 

Page 3 GAO-07-856T
The decision-making process for postmarket drug safety is complex, 

involving input from a variety of FDA staff and organizational units and 

information sources, but the central focus of the process is the iterative 

interaction between OND and ODS. OND is a much larger office than ODS. 

In fiscal year 2005, OND had 715 staff and expenditures of $110.6 million. 

More than half of OND’s expenditures in fiscal year 2005, or $57.2 million, 

came from user fees paid by drug sponsors under the Prescription Drug 

User Fee Amendments of 2002.6

 ODS had 106 staff in fiscal year 2005 and

expenditures of $26.9 million, with $7.6 million from prescription drug 

user fees. 

After a drug is on the market, OND staff receive information about safety 

issues in several ways. First, OND staff receive notification of adverse 

event reports for drugs to which they are assigned and they review the 

periodic adverse event reports that are submitted by drug sponsors.7

Second, OND staff review safety information that is submitted to FDA 

when a sponsor seeks approval for a new use or formulation of a drug, and 

monitor completion of postmarket studies. When consulting with OND on

a safety issue, ODS staff search for all relevant case reports of adverse 

events and assess them to determine whether or not the drug caused the

adverse event and whether there are any common trends or risk factors. 

ODS staff might also use information from observational studies and drug 

use analyses to analyze the safety issue. When completed, ODS staff 

summarize their analysis in a written consult. According to FDA officials, 

OND staff within the review divisions usually decide what regulatory 

action should occur, if any, by considering the results of the safety analysis

in the context of other factors such as the availability of other similar 

drugs and the severity of the condition the drug is designed to treat. Then, 

if necessary, OND staff make a decision about what action should be 

taken. 

Several CDER staff, including staff from OND and ODS, told us that most 

of the time there is agreement within FDA about what safety actions 

should be taken. At other times, however, OND and ODS staff disagree 

about whether the postmarket data are adequate to establish the existence 

of a safety problem or support a recommended regulatory action. In those 

 6

Pub. L. No. 107-188 § 501 et. seq., 116 Stat. 687. 

7

Health care providers and patients can voluntarily submit adverse event reports to FDA. 

Adverse event reports become part of FDA’s computerized database known as the Adverse 

Event Reporting System. 

Page 4 GAO-07-856T
cases, OND staff sometimes request additional analyses by ODS and 

sometimes there is involvement from other FDA organizations. In some 

cases, OND seeks the advice of FDA’s scientific advisory committees, 

which are composed of experts and consumer representatives from 

outside FDA.8

 In 2002, FDA established the Drug Safety and Risk 

Management Advisory Committee, 1 of the 16 human-drug-related 

scientific advisory committees, to specifically advise FDA on drug safety

and risk management issues. The recommendations of the advisory 

committees do not bind the agency to any decision. 

FDA has the authority to withdraw the approval of a drug on the market 

for safety-related and other reasons, although it rarely does so.9

 In almost 

all cases of drug withdrawals for safety reasons, the drug’s sponsor has 

voluntarily removed the drug from the market. For example, in 2001 

Baycol’s sponsor voluntarily withdrew the drug from the market after 

meeting with FDA to discuss reports of adverse events, including some 

reports of fatalities.10 FDA does not have explicit authority to require that 

drug sponsors take other safety actions; however, when FDA identifies a 

potential problem, sponsors generally negotiate with FDA to develop a 

mutually agreeable remedy to avoid other regulatory action. Negotiations 

may result in revised drug labeling or restricted distribution. FDA has 

limited authority to require that sponsors conduct postmarket safety 

studies. 

 8

These committees are either mandated by legislation or are established at the discretion of 

the Department of Health and Human Services (HHS). 

9

21 U.S.C. § 355(e). FDA may propose withdrawal when, for example, it determines through

experience, tests, or other data that a drug is unsafe under the conditions of use approved

in its application, there is a lack of substantial evidence that the drug will have the effect

that it purports to have or that is suggested in its labeling, or required patent information is 

not timely filed. Prior to withdrawal, FDA would need to notify the affected parties and 

provide an opportunity for a hearing. Approval may be suspended immediately, prior to a

hearing, if the Secretary of Health and Human Services finds that continued marketing of a 

particular drug constitutes an imminent hazard to the public health. 

10At this meeting FDA communicated to the sponsor that it was considering proceeding 

with a withdrawal of the highest dose of Baycol because of its increased risk for a severe 

adverse event involving the breakdown of muscle fibers. 

Page 5 GAO-07-856T
In our March 2006 report, we found that FDA’s postmarket drug safety 

decision-making process was limited by a lack of clarity, insufficient 

oversight by management, and data constraints. We observed that there 

was a lack of established criteria for determining what safety actions to 

take and when, and aspects of ODS’s role in the process were unclear. A 

lack of communication between ODS and OND’s review divisions and 

limited oversight of postmarket drug safety issues by ODS management 

hindered the decision-making process. FDA’s decisions regarding 

postmarket drug safety have also been made more difficult by the 

constraints it faces in obtaining data.

FDA Lacked a Clear 

and Effective 

Decision-making 

Process for 

Postmarket Drug 

Safety 

Decision-making Process 

on Drug Safety Lacked 

Clarity about Criteria for 

Action and the Role of 

ODS 

While acknowledging the complexity of the postmarket drug safety 

decision-making process, we found through our interviews with OND and 

ODS staff and in our case studies that the process lacked clarity about 

how drug safety decisions were made and about the role of ODS. If FDA 

had established criteria for determining what safety actions to take and 

when, then some of the disagreements we observed in our case studies 

might have been resolved more quickly. In the absence of established 

criteria, several FDA officials told us that decisions about safety actions 

were often based on the case-by-case judgments of the individuals 

reviewing the data. Our observations were consistent with two previous 

internal FDA reports on the agency’s internal deliberations regarding 

Propulsid and the diabetes drug Rezulin.11 In those reviews FDA indicated

that an absence of established criteria for determining what safety actions

to take, and when to take them, posed a challenge for making postmarket 

drug safety decisions. 

We also found that ODS’s role in scientific advisory committee meetings 

was unclear. According to the OND Director, OND is responsible for 

setting the agenda for the advisory committee meetings, with the 

exception of the Drug Safety and Risk Management Advisory Committee.12

This includes who is to present and what issues will be discussed by the 

advisory committees. For the advisory committees (other than the Drug 

Safety and Risk Management Advisory Committee) it was unclear when 

ODS staff would participate. 

 11Rezulin was removed from the market in 2000 because of its risk for liver toxicity. 

12ODS is responsible for setting the agenda for meetings of the Drug Safety and Risk 

Management Advisory Committee. 

Page 6 GAO-07-856T
A lack of communication between ODS and OND’s review divisions and 

limited oversight of postmarket drug safety issues by ODS management 

also hindered the decision-making process. ODS and OND staff often 

described their relationship with each other as generally collaborative,

with effective communication, but both ODS and OND staff told us that 

there had been communication problems on some occasions, and that this

had been an ongoing concern. For example, according to some ODS staff, 

OND did not always adequately communicate the key question or point of 

interest to ODS when it requested a consult, and as ODS worked on the 

consult there was sometimes little interaction between the two offices. 

After a consult was completed and sent to OND, ODS staff reported that 

OND sometimes did not respond in a timely manner or at all. Several ODS

staff characterized this as consults falling into a “black hole” or “abyss.” 

OND’s Director told us that OND staff probably do not “close the loop” in

responding to ODS’s consults, which includes explaining why certain ODS 

recommendations were not followed. In some cases CDER managers and

OND staff criticized the methods used in ODS consults and told us that the 

consults were too lengthy and academic. 

ODS management had not effectively overseen postmarket drug safety 

issues, and as a result, it was unclear how FDA could know that important 

safety concerns had been addressed and resolved in a timely manner. A 

former ODS Director told us that the small size of ODS’s management 

team presented a challenge for effective oversight of postmarket drug 

safety issues. Another problem was the lack of systematic information on 

drug safety issues. According to the ODS Director, ODS maintained a 

database of consults that provided some information about the consults 

that ODS staff conducted, but it did not include information about whether 

ODS staff made recommendations for safety actions and how the safety 

issues were handled and resolved, such as whether recommended safety 

actions were implemented by OND. 

A Lack of Communication 

and Limited Oversight 

Hindered the Decisionmaking Process 

Data Constraints Have 

Contributed to Difficulty in 

Making Postmarket Safety 

Decisions 

Data constraints—such as weaknesses in data sources and FDA’s limited 

ability to require certain studies and obtain additional data—have 

contributed to FDA’s difficulty in making postmarket drug safety 

decisions. OND and ODS have used three different sources of data to 

make postmarket drug safety decisions, including adverse event reports, 

clinical trial studies, and observational studies. While data from each 

source have weaknesses that have contributed to the difficulty in making 

postmarket drug safety decisions, evidence from more than one source 

can help inform the postmarket decision-making process. The availability 

of these data sources has been constrained, however, because of FDA’s 

Page 7 GAO-07-856T
limited authority to require drug sponsors to conduct postmarket studies 

and its resources. 

While decisions about postmarket drug safety have often been based on 

adverse event reports, FDA cannot establish the true frequency of adverse 

events in the population with data from adverse event reports. The 

inability to calculate the true frequency makes it hard to establish the 

magnitude of a safety problem, and comparisons of risks across similar 

drugs are difficult.13 In addition, it is difficult to attribute adverse events to 

particular drugs when there is a relatively high incidence rate in the 

population for the medical condition. It is also difficult to attribute adverse 

events to the use of particular drugs because data from adverse event 

reports may have been confounded by other factors, such as other drug 

exposures. 

FDA can also use available data from clinical trials and observational 

studies to support postmarket drug safety decisions. Although each source 

presents weaknesses that constrain the usefulness of the data provided, 

having data from more than one source can help improve FDA’s decisionmaking ability. Clinical trials, in particular randomized clinical trials, are 

considered the “gold standard” for assessing evidence about efficacy and

safety because they are considered the strongest method by which one can 

determine whether new drugs work.14 However, clinical trials also have 

weaknesses. Clinical trials typically have too few enrolled patients to 

detect serious adverse events associated with a drug that occur relatively 

infrequently in the population being studied. They are usually carried out 

on homogenous populations of patients that often do not reflect the types

of patients who will actually take the drugs. For example, they do not 

often include those who have other medical problems or take other 

medications. In addition, clinical trials are often too short in duration to 

identify adverse events that may occur only after long use of the drug. This 

is particularly important for drugs used to treat chronic conditions where 

patients are taking the medications for the long term. Observational 

 13This is due, in part, to the underreporting of adverse events and inconsistency in how

those reporting define cases. These limitations have been reported elsewhere. See, for

example, D. J. Graham, P. C. Waller, and X. Kurz, “A View from Regulatory Agencies,” in 

Brian L. Strom, ed., Pharmacoepidemiology (Chichester: John Wiley & Sons, Ltd., 2000),

pp. 109–124. 

14In these trials, patients are randomly assigned to either receive the drug or a different

treatment, and differences in results between the two groups can typically be attributed to 

the drug. 

Page 8 GAO-07-856T
studies, which use data obtained from population-based sources, can 

provide FDA with information about the population effect and risk 

associated with the use of a particular drug. 

We have found that FDA’s access to postmarket clinical trial and 

observational data is limited by its authority and available resources. FDA 

does not have broad authority to require that a drug sponsor conduct an 

observational study or clinical trial for the purpose of investigating a 

specific postmarket safety concern. One senior FDA official and several 

outside drug safety experts told us that FDA needs greater authority to 

require such studies. Long-term clinical trials may be needed to answer 

safety questions about risks associated with the long-term use of drugs. 

For example, during a February 2005 scientific advisory committee 

meeting, some FDA staff and committee members indicated that there was 

a need for better information on the long-term use of anti-inflammatory 

drugs and discussed how a long-term trial might be designed to study the 

cardiovascular risks associated with the use of these drugs.15

Lacking specific authority to require drug sponsors to conduct postmarket 

studies, FDA has often relied on drug sponsors voluntarily agreeing to

conduct these studies. But the postmarket studies that drug sponsors have 

agreed to conduct have not consistently been completed. One study 

estimated that the completion rate of postmarket studies, including those 

that sponsors had voluntarily agreed to conduct, rose from 17 percent in 

the mid-1980s to 24 percent between 1991 and 2003.16 FDA has little 

leverage to ensure that these studies are carried out. 

In terms of resource limitations, several FDA staff (including CDER 

managers) and outside drug safety experts told us that in the past ODS has 

not had enough resources for cooperative agreements to support its 

postmarket drug surveillance program. Under the cooperative agreement 

program, FDA collaborated with outside researchers in order to access a 

wide range of population-based data and conduct research on drug safety. 

Annual funding for this program was less than $1 million from fiscal year 

 15This was a joint meeting of the Arthritis Advisory Committee and the Drug Safety and 

Risk Management Advisory Committee. 

16Postmarket studies for approved drugs and biologics are included in the percent 

calculations. See: Tufts Center for the Study of Drug Development, Kenneth I. Kaitin, ed., 

“FDA Requested Postmarketing Studies in 73% of Recent New Drug Approvals,” Impact 

Report: Analysis and Insight into Critical Drug Development Issues, vol. 6, no. 4 (2004). 

Page 9 GAO-07-856T
2002 through fiscal year 2005. In 2006, FDA awarded four contracts for a 

total cost of $1.6 million per year to replace the cooperative agreements. 

Prior to the completion of our March 2006 report, FDA began several 

initiatives to improve its postmarket drug safety decision-making process. 

Most prominently, FDA commissioned the IOM to convene a committee of 

experts to assess the current system for evaluating postmarket drug 

safety, including FDA’s oversight of postmarket safety and its processes. 

IOM issued its report in September 2006.17 FDA also had underway several 

organizational changes that we discussed in our 2006 report. For example, 

FDA established the Drug Safety Oversight Board to help provide 

oversight and advice to the CDER Director on the management of 

important safety issues. The board is involved with ensuring that broader 

safety issues, such as ongoing delays in changing a label, are effectively 

resolved. FDA also drafted a policy that was designed to ensure that all

major postmarket safety recommendations would be discussed by 

involved OND and ODS managers, beginning at the division level, and 

documented.

18 FDA implemented a pilot program for dispute resolution 

that is designed for individual CDER staff to have their views heard when 

they disagree with a decision that could have a significant negative effect

on public health. Because the CDER Director is involved in determining 

whether the process will be initiated, appoints a panel chair to review the 

case, and makes the final decision on how the dispute should be resolved, 

we found that the pilot program does not offer CDER staff an independent 

forum for resolving disputes. FDA also began to explore ways to access 

additional data sources that it can obtain under its current authority, such 

as data on Medicare beneficiaries’ experience with prescription drugs 

covered under the prescription drug benefit.19

FDA’s Initiatives to 

Improve Postmarket 

Drug Safety Decision 

Making 

 17A. Baciu, K. Stratton, and S. P. Burke, eds., Institute of Medicine of the National 

Academies, Committee on the Assessment of the U.S. Drug Safety System, The Future of 

Drug Safety: Promoting and Protecting the Health of the Public (Washington, D.C.: 

Sept. 22, 2006). 

18The draft policy is entitled “Process for Decision-Making Regarding Major Postmarketing 

Safety-Related Actions.” 

19In October 2006, the Centers for Medicare & Medicaid Services published a proposed rule 

that would, when finalized, facilitate access by FDA and others to information about

prescription drugs covered by Medicare. See 71 Fed. Reg. 61445 (Oct. 18, 2006). 

Page 10 GAO-07-856T
Since our report, FDA has made efforts to improve its postmarket safety 

decision-making and oversight process. In its written response to the IOM 

recommendations, FDA agreed with the goal of many of the 

recommendations made by GAO and IOM.20 In that response, FDA stated 

that it would take steps to improve the “culture of safety” in CDER, reduce 

tension between preapproval and postapproval staff, clarify the roles and 

responsibilities of pre- and postmarket staff, and improve methods for 

resolving scientific disagreements. 

FDA has also begun several initiatives since our March 2006 report that we 

believe could address three of our four recommendations. Because none 

of these initiatives were fully implemented as of May 2007, it was too early 

to evaluate their effectiveness. 

• To make the postmarket safety decision-making process clearer and more 

effective, we recommended that FDA revise and implement its draft policy 

on major postmarket drug safety decisions. CDER has made revisions to 

the draft policy, but has not yet finalized and implemented it. CDER’s 

Associate Director for Safety Policy and Communication told us that the 

draft policy provides guidance for making major postmarket safety 

decisions, including identifying the decision-making officials for safety 

actions and ensuring that the views of involved FDA staff are documented.

According to the Associate Director, the revised draft does not now 

discuss decisions for more limited safety actions, such as adding a boxed 

warning to a drug’s label.21 As a result, fewer postmarket safety 

recommendations would be required to be discussed by involved OND and 

ODS managers than envisioned in the draft policy we reviewed for our 

2006 report. Separately, FDA has instituted some procedures that are 

consistent with the goals of the draft policy. For example ODS staff now 

participate in regular, bimonthly safety meetings with each of the review 

divisions in OND. 

 20HHS, FDA, The Future of Drug Safety—Promoting and Protecting the Health of the 

Public: FDA’s Response to the Institute of Medicine’s 2006 Report (Rockville, Md.:

January 2007). 

21The original draft policy included the market withdrawal of a drug, restrictions on a

drug’s distribution, and boxed warnings as major postmarket drug safety decisions. 

Page 11 GAO-07-856T
• To help resolve disagreements over safety decisions, we recommended 

that FDA improve CDER’s dispute resolution process by revising the pilot 

program to increase its independence. FDA had not revised its pilot 

dispute resolution program as of May 2007, and FDA officials told us that 

the existing program had not been used by any CDER staff member. 

• To make the postmarket safety decision-making process clearer, we 

recommended that FDA clarify ODS’s role in FDA’s scientific advisory 

committee meetings involving postmarket drug safety issues. According to 

an FDA official, the agency intends to, but had not yet, drafted a policy 

that will describe what safety information should be presented and how 

such information should be presented at scientific advisory committee 

meetings. The policy is also expected to clarify ODS’s role in planning for, 

and participating in, meetings of FDA’s scientific advisory committees. 

• To help ensure that safety concerns were addressed and resolved in a 

timely manner, we recommended that FDA establish a mechanism for 

systematically tracking ODS’s recommendations and subsequent safety 

actions. As of May 2007, FDA was in the process of implementing the 

Document Archiving, Reporting and Regulatory Tracking System 

(DARRTS) to track such information on postmarket drug safety issues. 

Among many other uses, DAARTS will track ODS’s safety 

recommendations and the responses to them. 

We also suggested in our report that Congress consider expanding FDA’s 

authority to require drug sponsors to conduct postmarket studies in order 

to ensure that the agency has the necessary information, such as clinical 

trial and observational data, to make postmarket decisions. 

Mr. Chairman, this concludes my prepared remarks. I would be pleased to 

respond to any questions that you or other members of the subcommittee 

may have. 

For further information regarding this testimony, please contact Marcia 

Crosse at (202) 512-7119 or crossem@gao.gov. Contact points for our 

Offices of Congressional Relations and Public Affairs may be found on the 

last page of this testimony. Martin T. Gahart, Assistant Director; Pamela 

Dooley; and Cathleen Hamann made key contributions to this statement. 

Page 12 GAO-07-856T
Page 13 GAO-07-856T

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