United States Government Accountability Office

GAO Testimony 

Before the Subcommittee on Oversight 

and Investigations, Committee on Energy 

and Commerce, House of Representatives

DRUG SAFETY 

FDA Needs to Further 

Address Shortcomings in Its 

Postmarket Decisionmaking Process 

Statement of Marcia Crosse 

Director, Health Care 

For Release on Delivery

Expected at 9:30 a.m. EDT

March 22, 2007

 

GAO-07-599T 
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

 March 22, 2007

DRUG SAFETY

FDA Needs to Further Address 

Shortcomings in Its Postmarket 

Decision-making Process 

Highlights of GAO-07-599T, a testimony 

before the Subcommittee on Oversight 

and Investigations, 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 the

effectiveness of FDA’s postmarket 

decision-making process. 

This testimony is based on Drug

Safety: Improvement Needed in 

FDA’s Postmarket Decisionmaking and Oversight Process, 

GAO-06-402 (March 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 and 

reviewed FDA documents in

February and March 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. 

Certain parts of ODS’s role in the process were unclear, including ODS’s 

participation in the meetings of scientific advisory committees organized by 

OND to discuss safety issues for specific drugs. In the case of Arava, for 

example, ODS staff were not allowed to present their analysis of postmarket 

safety at an advisory committee meeting held to review Arava’s safety risks 

and benefits. Insufficient communication between ODS and OND hindered 

the decision-making 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 there were weaknesses in the 

different types of data available to FDA, and FDA’s access to data was 

constrained by both its authority to require certain studies and its limited 

resources. 

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 that, if implemented, could 

address three of GAO’s four recommendations. Because none of these 

initiatives was fully implemented as of March 2007, it was too early to 

evaluate their effectiveness. 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-07-599T.

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 Food and Drug 

Administration’s (FDA) process for decision making regarding postmarket 

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

concerns about FDA’s 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 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. 

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-07-599T
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. 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. Certain parts of ODS’s role in the process were unclear, 

including ODS’s participation in scientific advisory committee meetings 

that were organized by OND to discuss specific drugs. Although ODS staff 

presented their analyses during some of these meetings, we found 

examples of the exclusion of ODS staff from making presentations at 

several meetings. For example, in 2003 ODS staff, who had recommended 

that Arava be removed from the market, were not allowed to discuss their 

analysis of Arava’s postmarket safety data at a scientific advisory 

committee meeting. This meeting was held to review Arava’s safety risks 

and benefits in the context of other similar drugs. 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 

 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-07-599T
and resolved in a timely manner. FDA 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 was also limited in the resources it had 

available to obtain data from outside sources. 

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. Although FDA’s initiatives 

are positive steps, they are not yet fully implemented and it is too soon to 

evaluate their effectiveness. 

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

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. 

Page 3 GAO-07-599T
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. 

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. 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.6 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 

 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. 

6

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-07-599T
about whether the postmarket data are adequate to establish the existence 

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

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.7

 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.8

 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.9

 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. 

 7

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

the Department of Health and Human Services. 

8

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. 

9

At 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-07-599T
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 were also made more difficult by the constraints it 

faced 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. For example, in the case of Bextra, ODS and OND staff 

disagreed about whether the degree of risk for serious skin reactions 

warranted a boxed warning, the most serious warning placed in the 

labeling of a prescription medication. Similarly, in the case of Propulsid, 

some staff, from both OND and ODS, supported proposing a withdrawal of 

approval because of the cardiovascular side effects of the drug while 

others believed label modifications were warranted.10 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 

 10Propulsid’s label was modified multiple times, including the addition of a boxed warning, 

to warn consumers and professionals about cardiovascular risks. 

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

Page 6 GAO-07-599T
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. Although ODS staff presented their 

postmarket drug safety analyses during some advisory committee 

meetings, our case study of Arava provided an example of the exclusion of

ODS staff. In March 2003, FDA’s Arthritis Advisory Committee met to 

review the efficacy of Arava, and its safety in the context of all available 

drugs to treat rheumatoid arthritis.13 The OND review division responsible 

for Arava presented its own analysis of postmarket drug safety data at the

meeting, but did not allow the ODS staff—who had recommended that 

Arava be removed from the market—to present their analysis because it

felt that ODS’s review did not have scientific merit. Specifically, the OND 

review division felt that some of the cases in the ODS review did not meet 

the definition of acute liver failure, the safety issue on which the review 

was focused.14

A Lack of Communication 

and Limited Oversight 

Hindered the Decisionmaking Process 

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.” 

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

Management Advisory Committee. 

13The committee was asked to consider whether the data presented by the drug’s sponsor

supported improvement in physical function and whether the drug’s labeling needed to be

updated to add any additional warning about liver toxicity. Ultimately, the label was 

strengthened in 2003 to state that rare cases of severe liver injury, including cases of fatal 

outcomes, had been reported in Arava users.

14Similarly, other senior-level CDER staff, including ODS and OND managers, did not agree 

with the ODS staff’s conclusions and recommendation. 

Page 7 GAO-07-599T
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. 

Data Constraints 

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—contributed 

to FDA’s difficulty in making postmarket drug safety decisions. OND and 

ODS used three different sources of data to make postmarket drug safety 

decisions. They included adverse event reports, clinical trial studies, and 

observational studies. While data from each source had weaknesses that 

contributed to the difficulty in making postmarket drug safety decisions, 

evidence from more than one source could have helped inform the 

postmarket decision-making process. The availability of these data 

sources was constrained, however, because of FDA’s limited authority to

require drug sponsors to conduct postmarket studies and its resources. 

While decisions about postmarket drug safety were often based on adverse 

event reports, FDA could not establish the true frequency of adverse 

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

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

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

Page 8 GAO-07-599T
drugs were difficult.15 In addition, it would have been difficult to attribute

adverse events to particular drugs when there was a relatively high 

incidence rate in the population for the medical condition. It was 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 constrained 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.16 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 

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. For example, in the case of

Propulsid, an observational study showed that a 1998 labeling change 

warning about contraindications did not significantly decrease the 

percentage of users in one population who should not have been 

prescribed this drug. Because they are not controlled experiments, 

 15This 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 

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

pp. 109–124. 

16In 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 9 GAO-07-599T
however, there is the possibility that the results can be biased or 

confounded by other factors. 

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

data was 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.17

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 

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 2003.18 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 

 17This was a joint meeting of the Arthritis Advisory Committee and the Drug Safety and 

Risk Management Advisory Committee. 

18Postmarket 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 10 GAO-07-599T
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 Institute of Medicine (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.

19 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—including those that involve disagreements—would be 

discussed by involved OND and ODS managers, beginning at the division 

level.20 The draft policy states that decisions about major postmarket 

safety recommendations would be documented. 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—including 

the failure to take a drug safety action—that could have a significant 

negative effect on public health. In that program, the CDER Director 

would decide whether the process should be initiated, appoint the chair 

for a panel to review the case, and make the final decision on how the 

dispute should be resolved. Because the CDER Director is involved in

determining whether the process will begin and makes the final decision, 

the pilot program did not offer employees 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 

FDA’s Initiatives to 

Improve Postmarket 

Drug Safety Decision 

Making 

 19Institute of Medicine of the National Academies, Committee on the Assessment of the

U.S. Drug Safety System, Editors A. Baciu, K. Stratton, and S.P. Burke, The Future of Drug 

Safety: Promoting and Protecting the Health of the Public (Washington, DC: 

Sept. 22, 2006). 

20The draft policy is entitled “Process for Decision-Making Regarding Major Postmarketing 

Safety-Related Actions.” 

Page 11 GAO-07-599T
Medicare beneficiaries’ experience with prescription drugs covered under 

the prescription drug benefit.21

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 goals of many of the 

recommendations made by GAO and IOM.22 In that response, FDA stated 

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

tension between pre-approval and post-approval 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 was fully implemented as of March 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.23 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. 

 21In 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). 

22HHS, 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). 

23The 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 12 GAO-07-599T
• 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 March 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 March 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. CDER’s Associate Director

for Safety Policy and Communication told us that DAARTS would be fully 

operational by the end of April 2007.

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. 

(290615) Page 13 GAO-07-599T
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