GAO 

United States Government Accountability Office

Report to the Ranking Member, 

Committee on Finance, U.S. Senate 

DRUG SAFETY 

FDA Has Begun 

Efforts to Enhance 

Postmarket Safety, 

but Additional Actions 

Are Needed 

November 2009 

GAO-10-68 
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

November 2009

DRUG SAFETY

FDA Has Begun Efforts to Enhance Postmarket 

Safety, but Additional Actions Are Needed 

Highlights of GAO-10-68, a report to the 

Ranking Member, Committee on Finance, 

U.S. Senate 

There have been long-standing 

concerns regarding the Food and 

Drug Administration’s (FDA) 

oversight of postmarket drug 

safety. In 2006, GAO reported that 

FDA had not clearly defined the 

roles of two offices involved in 

making decisions about postmarket 

safety—the Office of New Drugs 

(OND) and the Office of 

Surveillance and Epidemiology 

(OSE). GAO and others reported 

additional concerns such as 

limitations in the data FDA relies 

on to identify postmarket drug 

safety issues and the systems it 

uses to track such issues. At that 

time, GAO made recommendations, 

including that FDA improve the 

independence of its program for 

resolving scientific disputes related 

to postmarket drug safety. In 2007, 

legislation further expanded FDA’s 

postmarket responsibilities. This 

report examines the steps that FDA 

is taking to (1) enhance its 

processes for making decisions 

about the safety of marketed drugs, 

(2) improve access to data that 

help the agency identify drug safety 

issues, and (3) build its capacity to 

fulfill its postmarket drug safety 

workload. GAO reviewed FDA 

policies and planning documents, 

and interviewed FDA officials. 

What GAO Recommends

GAO recommends that FDA 

develop a comprehensive plan to 

prepare OSE for the transfer of 

additional regulatory authorities 

from OND. FDA agreed with GAO’s 

recommendation. 

FDA is beginning to address previously identified weaknesses in its oversight 

of postmarket drug safety issues, but challenges remain. The agency is 

changing its postmarket decision-making process as part of its Safety First 

Initiative, which includes formalizing interactions between OND and OSE and 

providing OSE with added responsibilities. The one authority FDA transferred 

from OND to OSE is a premarket review responsibility. FDA officials said the 

agency plans to transfer authority for two postmarket responsibilities for 

reviewing certain types of drug safety studies, but the agency does not have a 

time frame for their transfer. Officials said that OSE must still gain experience 

leading the one transferred responsibility and expand its staff before it can 

assume these additional responsibilities. While most of the OSE and OND 

employees GAO interviewed indicated that OSE’s role in managing safety 

issues has increased since 2006, most OSE employees GAO interviewed said 

that OND’s perspective still carries more weight in decision making. OND 

recently created safety management positions in each of its 17 divisions; OSE 

expanded its similar positions from 9 to 25, although an employee said 

turnover has made it difficult for the OSE managers to gain experience. FDA 

is also revising its program for resolving scientific disputes, but these changes 

have not increased its independence, as GAO recommended. 

FDA plans to implement new data systems and is increasing access to 

external data to assist with drug safety decisions. FDA plans to implement 

new systems in 2010 to improve the timeliness, quality, and analysis of reports 

of adverse events associated with human drug use. FDA has also increased 

funding for contracts with private companies and is in the early stages of 

forming partnerships with federal data holders to access external data. As 

mandated in the 2007 legislation, FDA is developing the Sentinel System, a 

network of external data providers intended to enhance drug safety 

surveillance, but the agency is in the early stages of developing it. 

FDA faces challenges meeting an expanding workload. The agency indicated 

that expanded responsibilities resulting from the 2007 legislation increased its 

workload, and both OND and OSE employees described difficulties meeting 

their responsibilities. FDA indicated that since fiscal year 2008, OND staff 

increased from 736 to 928 and OSE staff increased from 114 to 193. However, 

an agency review suggests that OSE may still need to more than double its 

staff of 193 by fiscal year 2011 to meet its new responsibilities. Although OSE 

has increased its staff, officials cited hiring challenges, such as competition 

from the private sector, that may make it difficult to hire staff quickly enough 

to meet the increasing workload. FDA also expects to complete a growing 

number of drug safety studies, but technological and staffing challenges limit 

its capacity to conduct these studies. To assist its decision making, FDA has 

increasingly sought advice from members of its external drug safety advisory 

committee. However, the agency has encountered difficulty filling several 

committee vacancies. An official said FDA is reviewing candidates with the 

goal of filling these vacancies as soon as possible. 

View GAO-10-68 or key components.

For more information, contact Marcia Crosse 

at (202) 512-7114 or crossem@gao.gov. 
Page i GAO-10-68 

Contents 

Letter 1

Background 4 

FDA Has Begun to Formalize Its Postmarket Decision-Making 

Process and Recently Implemented Oversight Initiatives, but 

Challenges Remain 16 

FDA Plans to Implement New Adverse Event Systems and Is 

Increasing Access to External Sources of Drug Safety Data 24 

Although Staff Has Recently Increased, FDA Faces Challenges 

Meeting Its Expanding Postmarket Safety Workload 31 

Conclusions 39 

Recommendation 40 

Agency Comments and Our Evaluation 40 

Appendix I Status of FDA Actions Related to Our 2006 

Recommendations 42 

Appendix II Comments from the Department of Health and 

Human Services 44 

Appendix III GAO Contact and Staff Acknowledgments 48 

Table 

Table 1: Selected Data Sources FDA Uses to Inform Its Drug Safety 

Decision Making 9 

Figure 

Figure 1: OSE and OND Funding, Fiscal Years 2004 through 2009 15 

 Postmarket Drug Safety 
Abbreviations 

AERS Adverse Event Reporting System 

CDER Center for Drug Evaluation and Research 

CMS Centers for Medicare & Medicaid Services 

DARRTS Document Archiving, Reporting, and Regulatory 

 Tracking System 

DCI data collection instrument 

DOD Department of Defense 

DPO differing professional opinion 

DSaRM Drug Safety and Risk Management Advisory Committee 

ESG Electronic Submissions Gateway 

FAERS FDA Adverse Event Reporting System 

FDA Food and Drug Administration 

FDAAA Food and Drug Administration Amendments Act of 2007 

HHS Department of Health and Human Services 

IOM Institute of Medicine 

MOA memorandum of agreement 

OIG Office of Inspector General 

OND Office of New Drugs 

OSE Office of Surveillance and Epidemiology 

PDUFA Prescription Drug User Fee Act of 1992 

REMS Risk Evaluation and Mitigation Strategy 

VA Department of Veterans Affairs 

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Page ii GAO-10-68 Postmarket Drug Safety
Page 1 GAO-10-68 

 

United States Government Accountability Office

Washington, DC 20548 

 

November 9, 2009 

The Honorable Charles E. Grassley 

Ranking Member 

Committee on Finance 

United States Senate 

Dear Senator Grassley: 

Concerns about the Food and Drug Administration’s (FDA) management 

of safety issues for drugs approved for marketing have been longstanding.1

 Reviews dating back over 30 years have identified problems 

related to the agency’s monitoring of postmarket drug safety.2

 In 2004, 

high-profile drug safety cases continued to raise concerns about FDA’s 

process for evaluating postmarket safety and making decisions about what 

actions to take. For example, FDA was criticized for taking too long to 

inform patients of serious drug risks. There were also reports of 

disagreements within the agency about how to address certain safety 

issues and reports that some FDA scientists were discouraged by 

supervisors from raising questions about the safety of certain drugs. FDA’s 

process for making postmarket drug safety decisions involves multiple 

offices, including the Office of New Drugs (OND) and the Office of 

Surveillance and Epidemiology (OSE). OND is involved in drug review 

activities throughout the life cycle of a drug (that is, premarket and 

postmarket). For postmarket safety issues, OND’s activities include 

interacting with OSE,3

 which evaluates and monitors drug risks and 

promotes the safe use of drugs. 

1

FDA is an agency within the Department of Health and Human Services (HHS). Within 

FDA, the Center for Drug Evaluation and Research (CDER) is responsible for overseeing 

the safety and effectiveness of drugs. 

2

See, for example, National Research Council, Report of the International Conference of 

Adverse Reactions Reporting Systems (Washington, D.C.: National Academies of Science, 

1971); FDA, Program Review of the Division of Epidemiology and Surveillance (DES) in 

the Office of Epidemiology and Biometrics (OEB) (Washington, D.C.: 1993); and HHS, 

Office of Inspector General, Review of the Food and Drug Administration’s Handling of 

Adverse Drug Reaction Reports (Washington, D.C.: December 1999). 

3

OSE was formerly known as the Office of Drug Safety. The office was renamed in May 

2006. In this report, we refer to the office by its current name. 

 Postmarket Drug Safety 
 

Since these concerns were raised, we and other organizations have 

conducted reviews of FDA’s process for monitoring the safety of marketed 

drugs. In 2006, we reported that FDA had not clearly defined the role of 

OSE in postmarket drug safety and communication problems between 

OND and OSE had hindered the decision-making process.4

 We also found 

weaknesses in the data that FDA relied on to identify postmarket drug 

safety issues and in the systems it used to track them once they were 

identified. In addition, a 2006 Institute of Medicine (IOM) report identified 

similar weaknesses. IOM also reported that FDA’s resources for 

postmarket drug safety were inadequate and that this could impede the 

agency’s ability to identify and take actions to address drug safety issues.5

More recently, HHS’s Office of Inspector General (OIG) identified 

oversight of drug safety as one of HHS’s top management challenges and 

earlier this year we added FDA’s oversight of drugs and other medical 

products to our list of high-risk federal programs.6

You raised questions about FDA’s postmarket drug safety program and 

asked that we follow up on our 2006 report to examine the role of OND 

and OSE in the postmarket monitoring of drugs. This report examines the 

steps that FDA is taking to (1) enhance its processes for making decisions 

about the safety of marketed drugs, (2) improve access to data that help 

the agency identify drug safety issues, and (3) build its capacity to fulfill its 

postmarket drug safety workload. 

To describe the steps FDA is taking to enhance its processes for making 

decisions about the safety of marketed drugs, we reviewed FDA policies 

and planning documents and interviewed officials to identify specific 

actions being taken by the agency.7

 We also interviewed all individuals 

 

4

GAO, Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and 

Oversight Process, GAO-06-402 (Washington, D.C.: Mar. 31, 2006). 

5

A. 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). 

6

HHS, Fiscal Year 2008 Agency Financial Report (November 2008), 

http://www.hhs.gov/afr/ (accessed Dec. 17, 2008); and GAO, High-Risk Series: An Update, 

GAO-09-271 (Washington, D.C.: January 2009). 

7

Our work is focused on human drugs regulated by CDER and not on biologics. Biologics 

are materials, such as vaccines, derived from living sources such as humans, animals, and 

microorganisms. Some biologics are regulated by CDER and such products are included in 

the scope of our work. 

Page 2 GAO-10-68 Postmarket Drug Safety
 

who were members of FDA’s drug safety advisory committee of external 

experts, the Drug Safety and Risk Management Advisory Committee 

(DSaRM), as of January 2009. In addition, we examined policies related to 

FDA’s program for resolving professional scientific disputes and 

interviewed FDA officials about its utilization by employees. To describe 

steps FDA is taking to improve access to data that help the agency identify 

drug safety issues, we reviewed documentation describing the 

development and implementation of systems the agency uses for 

collecting and monitoring drug safety data. We also examined contracts 

FDA has entered into with external organizations and agreements with 

federal agencies to access information about drug use and patient 

outcomes. To describe the steps that FDA is taking to build its capacity to 

fulfill its postmarket drug safety workload, we reviewed staffing data 

provided by the agency and documents related to the agency’s efforts to 

assess workload. We also interviewed FDA officials regarding hiring 

initiatives to meet its postmarket drug safety responsibilities. 

In addition, to supplement our work for each of the three objectives, we 

conducted a series of interviews with small groups of OND and OSE 

employees with responsibilities involving postmarket drug safety. Each 

small group interview consisted of a group discussion to capture general 

themes about these activities. At the conclusion of each interview, we 

asked each employee to complete a written data collection instrument 

(DCI) to document their responses to specific questions about the 

agency’s postmarket decision-making process. To select employees for our 

small group interviews, we obtained March 2009 staffing data from FDA 

and confirmed the accuracy of these data through discussions with 

officials from OND and OSE. We also used our discussions with the OND 

and OSE officials to help us identify employees with no management 

responsibilities and at least 4 years of experience in the Center for Drug 

Evaluation and Research (CDER). We selected these employees because 

they are directly engaged in postmarket safety activities and would be in a 

position to comment on changes made by the agency since our 2006 

report. 

• For OND, we selected employees from its four divisions with the largest 

number of employees,8

 which we identified using the March 2009 staffing 

 

8

OND has a total of 17 review divisions. We selected individuals from the Divisions of 

Anesthesia, Analgesia, and Rheumatology Products; Drug Oncology Products; 

Gastroenterology Products; and Neurology Products. 

Page 3 GAO-10-68 Postmarket Drug Safety
 

data. We determined that these data were sufficiently reliable for the 

purpose of our report. For each division, we randomly selected to 

interview five medical reviewers, who are the individuals responsible for 

reviewing data on the safety and efficacy of drugs. In one division, we also 

spoke with a second group of reviewers because that division has 

established separate teams of general reviewers and reviewers with 

specific drug safety responsibilities.9

 Based on these selection criteria and 

the availability of employees, we conducted five small group interviews of 

four or five employees, each. 

• For OSE, we selected all employees from each of the office’s five divisions 

who met our criteria to interview. For one division, we divided employees 

into two interview groups because of the large number of employees 

meeting our selection criteria. Based on these selection criteria and the 

availability of employees, we conducted six small group interviews of 

between three and six employees, each. 

Across all of the small groups, we interviewed a total of 52 employees, 

each of whom completed a DCI. The views expressed by these employees 

cannot be generalized to all employees working within these offices. 

We conducted this performance audit from October 2008 through October 

2009 in accordance with generally accepted government auditing 

standards. Those standards require that we plan and perform the audit to 

obtain sufficient, appropriate evidence to provide a reasonable basis for 

our findings and conclusions based on our audit objectives. We believe 

that the evidence obtained provides a reasonable basis for our findings 

and conclusions based on our audit objectives. 

Before a drug can be marketed in the United States, its sponsor must 

demonstrate to FDA that the drug is safe and effective for its intended use. 

FDA approves a drug for marketing when the agency judges that its known 

benefits outweigh its known risks. However, because premarket 

evaluations are limited in their ability to always predict safety and efficacy 

with absolute certainty, FDA continues to assess a drug’s risks and 

benefits after it has been marketed. If the agency identifies a postmarket 

safety issue, it makes a decision regarding whether to take a regulatory 

Background 

 

9

The Division of Neurology Products has medical reviewers who fulfill traditional review 

duties and those who are members of a safety review team. Therefore, we conducted 

separate interviews with each of these groups of medical reviewers. 

Page 4 GAO-10-68 Postmarket Drug Safety
 

action, such as withdrawing the approval of a drug, which it rarely does, or 

communicating new safety information to the public and healthcare 

providers. 

FDA Organization Related 

to Postmarket Drug Safety 

Decision Making 

The decision-making process for postmarket drug safety is complex, 

multidisciplinary, and relies on an iterative interaction between OND, 

OSE, and other FDA components.10 OND, which primarily conducts 

premarket reviews of drug applications submitted by drug sponsors, also 

has postmarket drug safety as one of its responsibilities. Although it 

interacts with OSE and staff from other offices concerning the postmarket 

safety of drugs, OND has ultimate responsibility to decide whether to take 

regulatory action regarding these issues. The office is organized into 17 

review divisions that generally reflect certain therapeutic areas, such as 

gastroenterology or oncology drugs. The review of safety and efficacy data 

from drug applications is conducted by OND medical reviewers, who 

typically are physicians who have expertise in specific therapeutic areas 

and are skilled in the review of clinical trials. 

OSE’s primary focus is on postmarket safety, although it is also involved in 

certain premarket drug safety issues. OSE has traditionally operated 

primarily in a consultant capacity to OND and has not had any 

independent decision-making responsibility. When a safety issue is 

identified, OSE staff may conduct an analysis and produce a written report 

called a “consult” to assist OND. Safety consults could include analyses of 

adverse event reports and assessments of postmarket study designs.11 In 

contrast to OND’s organization by therapeutic area, OSE is organized into 

five divisions that each reflect different areas of its drug safety 

responsibilities. Two divisions analyze adverse event reports, one division 

reviews epidemiologic studies completed by drug sponsors and conducts 

its own studies,12 one division reviews risk management plans submitted 

by drug sponsors,13 and one division reviews proposed proprietary drug 

 

10FDA indicated that, in addition to OND and OSE, other FDA offices and divisions, such as 

the Office of Compliance, the Office of Clinical Pharmacology, and the Office of 

Biotechnology Products, are routinely involved in postmarket decision making. 

11The term “adverse event” is used by FDA to indicate any untoward medical event that is 

associated with the use of a drug, whether causally related to the drug or not. 

12Epidemiologic studies are intended to provide information about the association between 

drug use and adverse events by allowing observation of care delivered in the population. 

13Risk management plans are submitted by drug sponsors and document plans for 

developing and implementing tools to minimize a drug’s risks while preserving its benefits. 

Page 5 GAO-10-68 Postmarket Drug Safety
 

names submitted by drug sponsors for their new products and postmarket 

studies of medication errors completed by drug sponsors and others.14

To help it provide oversight of important, high-level safety decisions, FDA 

established the Drug Safety Oversight Board in spring 2005.15 The board is 

comprised primarily of FDA staff, including OND and OSE officials, but 

also includes officials from other federal agencies, such as the National 

Institutes of Health. It was established with the goal of providing 

independent oversight and making recommendations to the CDER 

Director about the management of important drug safety issues.16

An important part of the drug approval and postmarket monitoring 

process is the advice the agency receives from CDER’s 16 drug-related 

scientific advisory committees composed of external experts.17 The 

committees are generally organized into specific therapeutic areas, such as 

gastrointestinal drugs or oncologic drugs. In 2002, FDA established 

DSaRM, which is one of the 16 committees. In contrast to the committees 

focused on a specific therapeutic area, DSaRM was established to advise 

FDA on drug safety and risk management issues across therapeutic areas. 

The committee’s charter states that DSaRM is to be composed of 14 

members—13 voting members with drug safety expertise and 1 nonvoting 

member to represent the drug industry. DSaRM members can also be 

asked to participate in other scientific advisory committee meetings when 

safety issues are discussed. OSE sets the agenda for DSaRM meetings, 

whereas OND sets the agenda for meetings of the other 15 committees. 

 

14OSE provides premarketing reviews of proprietary drug names to minimize any potential 

conflicts with names of drugs already being marketed that could lead to a healthcare 

provider misprescribing or misinterpreting the correct name, and dispensing or 

administering the wrong product, or dispensing it incorrectly. The office also reviews drug 

labeling and packaging in order to reduce the potential for a medication error. 

15The Drug Safety Oversight Board has since been mandated by law. See 21 U.S.C. § 355-

1(j). 

16The Drug Safety Oversight Board also has responsibility to, among other things, manage 

the dissemination of certain safety information through FDA’s Web site to healthcare 

professionals and patients; establish policies regarding management of drug safety issues 

in CDER; and track important emerging safety issues and ensure that they are resolved in a 

timely manner. 

17In addition, the Pediatric Review Committee, an FDA-wide committee, also focuses on 

postmarket safety for drugs and biologics. FDA advisory committee members can be 

medical professionals, scientists, researchers, industry leaders, consumers, or patients. 

Page 6 GAO-10-68 Postmarket Drug Safety
 

Advisory committees may make recommendations to FDA that are not 

binding on the agency’s decision making. 

If individuals within CDER have differences of professional opinion or 

scientific disputes regarding a decision taken by the agency, they are 

generally expected to try to resolve them through their supervisory chain. 

If staff cannot resolve the dispute through this process, they can access 

CDER’s differing professional opinion (DPO) program.18 First 

implemented as a pilot program in November 2004, it provides a process 

through which individuals can protest agency actions or inaction when 

they believe there is a risk of a significant negative impact on public 

health. Under this process, a dispute filed by a CDER employee could be 

reviewed by an ad hoc panel of three to four employees.19 The panel chair,

who is appointed by the CDER Director, appoints the additional members

one of whom is nominated by the employee initiating the dispute. The 

panel would make a recommendation for resolving the dispute to the 

CDER Director. Several elements of this process are overseen by the 

CDER Ombudsman’s Office, in consultatio

, 

n with the CDER Director.20

 

Data That Inform FDA’s 

Postmarket DecisionMaking Process 

FDA uses evidence from multiple data sources to inform its postmarket 

decision-making process, each of which has certain strengths and 

weaknesses. FDA uses randomized clinical trial data to assess drug safety 

prior to approval. However, these data have inherent weaknesses. 

Therefore, the agency uses other data to continue to assess drug safety 

once drugs are on the market. One method of assessing postmarket drug 

safety is through the collection and analysis of reports of adverse events 

associated with drug use. FDA requires drug sponsors to submit adverse 

18In our prior report, we referred to multiple FDA processes for resolving scientific 

disputes as “dispute resolution processes,” including what FDA terms as its DPO program. 

See GAO-06-402. For the purposes of this report, we use the term “dispute resolution” to 

refer to the broad category of processes involved in resolving scientific disputes, including 

the review of the dispute by the supervisory chain and DPO program. 

19When appropriate and feasible, a member with relevant technical expertise who is 

external to the agency could also be chosen. 

20In addition to these duties, CDER’s Ombudsman receives inquiries and investigates 

complaints from the drug industry, consumers, and healthcare professionals and provides 

general information on product development and regulation. In 2008, 94 percent of the 

contacts received by the Ombudsman were from the drug industry and consumers and 

6 percent were from FDA employees. 

Page 7 GAO-10-68 Postmarket Drug Safety
 

event reports for the drugs they market.21 In addition, healthcare providers 

and patients may voluntarily submit adverse event reports to FDA’s 

Medwatch program by telephone, by mailing or faxing a paper form, or 

through a Web-based application on the Medwatch Web site. In 1997, 

CDER implemented the Adverse Event Reporting System (AERS), which it 

uses to store reports of adverse events. Adverse events are often a basis 

for postmarket safety actions; however, adverse event reporting has 

limitations that make it hard to establish the magnitude of a safety 

problem or to compare risks across similar drugs. Therefore, once a 

“safety signal” is identified for a marketed drug,22 FDA may use data from 

observational epidemiologic studies to further examine relationships 

between a drug’s use and reported adverse events. To conduct these 

studies, the agency seeks data from large, external databases of electronic 

health information—including claims data collected by health insurance 

companies and electronic medical records of care provided through large 

healthcare systems. (See table 1 for a description of these data sources 

used to inform drug safety decision making before and after approval.) 

 

21See 21 C.F.R. §§ 310.305, 314.80, 314.98, 600.80 (2009). 

22Safety signals, which are potential relationships between drug use and adverse events, are 

sometimes the first indicator of a potential drug safety problem. 

Page 8 GAO-10-68 Postmarket Drug Safety
 

Table 1: Selected Data Sources FDA Uses to Inform Its Drug Safety Decision Making 

Market status 

Premarket: approval Postmarket: signal generation Postmarket: signal confirmation 

Data source Randomized clinical trials Adverse event reports Observational studies 

Description Studies that randomly assign patients 

to either a treatment group that 

receives a drug or a control group 

that does not receive that drug. 

Reports of adverse events received 

from patients, healthcare providers, 

and drug manufacturers once a drug 

is on the market. 

Studies in which patients are not 

assigned to groups, but are studied 

as they receive treatment, such as, 

epidemiologic studies using data 

from large databases of electronic 

health information (insurance or 

medical records). 

Use To assess drug safety and efficacy. To generate “safety signals,” which 

are potential relationships between 

use of a drug and an adverse event. 

To confirm safety signals by further 

investigation of the relationship 

between the drug and the adverse 

event. 

Strengths Randomization minimizes differences 

between the groups at the outset, 

which typically allows outcome 

differences to be attributed to the 

treatment. 

Provides valuable information on 

rare, unexpected adverse events, 

including events that occur in patients 

other than those tested in clinical 

trials. 

May involve larger groups of typical 

patients over longer periods of time, 

in more “real world” settings. 

Weaknesses • Generally involve a small group 

of patients relative to the 

population that will ultimately use 

the drug. 

• Patients typically receive the 

drug over a short duration. 

• Elderly persons, pregnant 

women, and patients who have 

other medical problems may be 

excluded, thus enrolled patients 

may not reflect the patients who 

will take the drug. 

• Not effective for attributing 

common events, such as heart 

attack, to drug use. 

• Adverse events are 

underreported and, for some 

drugs, FDA may not have 

access to the total number of 

people exposed, which makes 

estimating the magnitude of a 

safety problem difficult. 

• There could be systematic 

differences between the 

treatment and control groups at 

the outset that account for 

outcome differences. 

• Concomitant use of other 

products, such as over-thecounter drugs or herbal 

supplements, may not be 

recorded in the databases, which 

could affect study results. 

Source: GAO. 

Note: This table presents examples of data sources that FDA may consult during the life cycle of a 

drug. FDA may use multiple data sources to evaluate a safety issue at any given time. For example, 

although clinical trial data are used to evaluate premarket safety, FDA also uses clinical trial data to 

evaluate postmarket drug safety. 

Recent Reviews of FDA’s 

Postmarket Drug Safety 

Oversight 

In 2006, we reported that FDA’s process for overseeing postmarket drug 

safety was limited by a lack of clarity about OSE’s role in decision making. 

For example, while OSE often made recommendations to OND in the 

consults that it completed, the agency had no policy explicitly stating 

whether this was part of OSE’s role. OSE staff also reported that these 

consults sometimes fell into a “black hole” or “abyss” and OSE staff would 

not be informed of the results of their recommendations. Also in 2006, IOM 

noted that an imbalance in authority, formal role, and resources between 

Page 9 GAO-10-68 Postmarket Drug Safety
 

OND and OSE constituted a major obstacle to a healthy organizational 

culture in CDER. Furthermore, IOM reported that FDA’s challenges are 

reflective of how premarket and postmarket functions have been divided 

historically. OSE generally takes a population-based perspective in their 

drug safety work by utilizing adverse event reporting and observational 

studies, while OND generally takes a clinical perspective that focuses 

primarily on randomized clinical trials. They reported that OND staff often 

view the observational data used by OSE as “soft” and unconvincing, while 

OSE staff view these data as informative and carrying great weight. IOM 

noted that the imbalance in roles and responsibilities denoted a 

subservience of the safety function and a devaluation of OSE’s discipline 

and approach by agency management. 

We also identified several specific limitations to FDA’s postmarket 

decision-making process. Several years prior to the release of our 2006 

report, FDA started drafting a policy intended to clarify the role of staff, 

including those from OSE, in the decision-making process. However, the 

policy had not been finalized and implemented by the time our 2006 report 

was issued. In addition, we reported that the role of OSE staff in planning 

for and participating in advisory committee meetings, other than those 

involving DSaRM, was not clear. We also found that the DPO program had 

not been used and may not have been viewed as sufficiently independent 

because it did not offer employees a forum for resolving disputes that was 

independent of the CDER Director. We reported, for example, that the 

CDER Director would help decide whether a dispute warranted review 

and would also make the final decision about how the dispute would be 

resolved. 

We also found that OSE management had not effectively overseen 

postmarket drug safety and lacked systematic information on this process. 

Specifically, although OSE maintained a database of consult requests it 

received from OND, the database did not include information about 

whether OSE staff had made recommendations to OND regarding safety 

actions. It also did not include information on how the safety issues were 

resolved, including whether OSE’s recommended safety actions were 

implemented by OND. In addition, in 2006, OIG found weaknesses in the 

extent to which FDA tracked another element of postmarket drug safety, 

the progression of postmarketing studies that FDA had requested drug 

sponsors to complete. OIG found that FDA could not readily identify 

Page 10 GAO-10-68 Postmarket Drug Safety
 

whether or how timely these studies were progressing toward 

completion.23

We also found in 2006 that FDA faced constraints in its access to data that 

allow it to monitor the safety of marketed drugs. For example, FDA staff 

and external drug safety experts told us that OSE did not have enough 

funding to support the purchase of data for postmarket drug surveillance. 

Similarly, IOM found that funding for purchasing data was severely limited 

and had changed little in over 20 years. IOM also found that FDA devoted 

limited resources for staff training and supportive technology that was 

needed to fully utilize purchased data. Furthermore, IOM concluded that 

AERS was outdated and inefficient and the agency had given little 

attention to using systematic methods for screening AERS for adverse 

events. 

We made multiple recommendations to FDA in 2006 that were intended to 

improve its oversight of postmarket drug safety. We recommended that 

FDA 

• revise and implement its draft policy on major postmarket drug safety 

decisions, 

• clarify OSE’s role in FDA’s scientific advisory committee meetings 

involving postmarket drug safety issues, 

• improve CDER’s dispute resolution process by revising the DPO program 

to increase its independence, and 

• establish a mechanism for systematically tracking OSE’s 

recommendations and subsequent safety actions. 

(See app. I for a summary of FDA actions taken in response to these 

recommendations.) 

 

23HHS Office of Inspector General, FDA’s Monitoring of Postmarketing Study 

Commitments (June 2006), downloaded from http://www.oig.hhs.gov/oei/reports/oei-01-04-

00390.pdf (accessed Aug. 6, 2008). 

Page 11 GAO-10-68 Postmarket Drug Safety
 

The Food and Drug Administration Amendments Act of 2007 (FDAAA) 

provided the agency with additional responsibilities intended to improve 

its oversight of postmarket drug safety.24 For example, FDAAA provided 

FDA with new authority to require drug sponsors to complete 

postmarketing studies to identify a serious risk or assess a known serious 

risk.25 Prior to the enactment of FDAAA, FDA only had the authority in 

limited circumstances to require drug sponsors to conduct a postmarket 

drug safety study;26 outside of these circumstances, the agency could 

request that drug sponsors voluntarily agree to conduct such studies. 

FDAAA also provided FDA with new authority to require drug sponsors to 

complete risk management plans. Previously, FDA issued guidance to drug 

sponsors to assist in the development of voluntary risk management plans. 

FDA may now require drug sponsors to implement a risk management 

plan through specific approaches, known as a Risk Evaluation and 

Mitigation Strategy (REMS).27 FDAAA also provided the agency with 

authority to impose civil monetary penalties on drug sponsors who violate 

these requirements.28

Changes to FDA’s 

Postmarket Drug Safety 

Authority and Funding 

FDAAA also requires FDA to conduct several other postmarket drug safety 

activities. For example: 

• FDA must, in collaboration with public, academic, and private entities, 

develop a postmarket risk identification and analysis system that can be 

used to analyze safety data from multiple sources.29

• FDA is required to screen AERS biweekly and publish quarterly reports of 

new safety information or potential signals of serious risks associated with 

the use of a drug.30

 

24Pub. L. No. 110-85, 121 Stat. 823. 

2521 U.S.C. § 355(o). 

26Prior to FDAAA, FDA had the authority in limited situations to require that sponsors 

commit to conducting postmarketing studies as a condition of approval. See 21 U.S.C. 

§ 356(b)(2). For example, in certain cases where human efficacy studies of a drug may not 

be ethical or feasible, FDA may rely on animal studies alone to approve the use of a drug 

and require postmarket studies as a condition of approval when studies on humans become 

feasible and ethical. 21 C.F.R. § 314.610(b)(1)(2009). 

2721 U.S.C. § 355-1. 

2821 U.S.C. § 333(f)(4). 

2921 U.S.C. § 355(k)(3). 

3021 U.S.C. § 355(k)(5). 

Page 12 GAO-10-68 Postmarket Drug Safety
 

• FDA is required to use DSaRM to seek input on certain activities, such as 

elements of REMS and the analysis of drug safety data.31

In addition to increasing FDA’s authorities, FDAAA also reauthorized the 

Prescription Drug User Fee Act of 1992 (PDUFA).32 Originally, PDUFA 

authorized FDA to collect user fees33 from drug sponsors in order to 

support the review of drug applications and it established performance 

goals, such as time frames for the review of applications. The increase in 

attention to timely drug approval decisions led to greater awareness of the 

need for FDA to strengthen its monitoring of postmarket drug safety, 

which was reflected in the 2002 reauthorization of PDUFA.34 The most 

recent authorization of PDUFA, in September 2007 as part of FDAAA, 

expanded the postmarket drug safety activities for which FDA is 

authorized to apply user fees.35 For example, the law identified the 

development of adverse event data collection systems as an activity that 

could be funded through user fees. In addition to amounts authorized to be 

used for all user fee activities, both premarket and postmarket, the PDUFA 

reauthorization identified specific annual fee revenues to be used for 

postmarket drug safety activities. In total, FDA reported that it plans to 

increase its allocation of annual user fees to support postmarket drug 

safety from about $54 million in fiscal year 2008 to about $102 million in 

fiscal year 2012.36

 

3121 U.S.C. § 355-1(f)(5). 

32See Pub. L. No. 110-85, §§ 101-109, 121 Stat. 823, 825-42. 

33Under PDUFA, FDA receives user fees from the pharmaceutical industry as part of its 

annual appropriation for salaries and expenses. To delineate the source of the appropriated 

funds in this report, we use the terms “user fee funding” to describe amounts derived from 

user fee collections, and “fiscal year appropriations” to describe amounts derived from the 

General Fund of the Treasury. Both user fee funding and fiscal year appropriations are 

made available through the annual appropriations process. 

34See Pub. L. No. 107-188, §§ 501-509, 116 Stat. 594, 687-94. 

35See 21 U.S.C. § 379g(6)(F). 

36FDA, Prescription Drug User Fee Act (PDUFA) IV Drug Safety Five-Year Plan, December 

2008, http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/ 

UCM119244.pdf, (accessed July 16, 2009). According to FDA, these user fee funds were 

allocated to CDER, the Center for Biologics Evaluation and Research, and other 

components of the agency. 

Page 13 GAO-10-68 Postmarket Drug Safety
 

Overall premarket and postmarket funding for OSE and OND increased 

since fiscal year 2006.37 From fiscal year 2006 through fiscal year 2008, 

OSE funding increased from about $31 million to about $71 million. During 

that same period, OND funding increased from about $115 million to 

$144 million. For both OSE and OND, much of the increase occurred in 

fiscal year 2008 and can be attributed to increased user fees. (See fig. 1.) 

Additionally, across all of CDER, funding for postmarket drug safety 

increased from about $54 million in fiscal year 2006 to $139 million in 

fiscal year 2008. Of the $139 million in fiscal year 2008, about $84 million 

was from fiscal year appropriations and $55 million was from user fees. 

 

37FDA was not able to provide OSE and OND funding specifically for postmarket drug 

safety. However, based on a fiscal year 2004 study, it estimated that OSE devoted about 

91 percent of its work time to postmarket drug safety, while OND devoted about 

11 percent. 

Page 14 GAO-10-68 Postmarket Drug Safety
 

Figure 1: OSE and OND Funding, Fiscal Years 2004 through 2009 

Source: GAO analysis of FDA data.

0

20

40

60

80

100

120

140

160

180

OSE user fees

OSE fiscal year appropriations

2009

estimate

2004 2005 2006 2007 2008

Dollars (in millions)

Fiscal year

OSE funding

0

20

40

60

80

100

120

140

160

180

OND user fees

OND fiscal year appropriations

2009

estimate

2004 2005 2006 2007 2008

Dollars (in millions)

Fiscal year

OND funding

User fees

Fiscal year appropriations

Note: Under PDUFA, FDA receives user fees from the pharmaceutical industry as part of its annual 

appropriation for salaries and expenses. We use the terms “user fee funding” to describe amounts 

derived from user fee collections and “fiscal year appropriations” to describe amounts derived from 

the General Fund of the Treasury to delineate the source of the appropriated funds. Both user fee 

funding and fiscal year appropriations are made available through the annual appropriations process. 

Page 15 GAO-10-68 Postmarket Drug Safety
 

FDA has begun to implement a new process and initiatives intended to 

clarify roles related to postmarket safety decision making, but faces a 

variety of challenges. Several initiatives have not been fully implemented 

and the agency has not increased the independence of its dispute 

resolution program. 

FDA Has Begun to 

Formalize Its 

Postmarket DecisionMaking Process and 

Recently 

Implemented 

Oversight Initiatives, 

but Challenges 

Remain 

FDA Has Begun to 

Formalize OND and OSE’s 

Decision-Making Process 

for Postmarket Drug 

Safety, but a Time Frame 

for Implementing Key 

Elements Has Yet to Be 

Established 

To enhance postmarket drug safety, FDA has begun to formalize 

interactions between OND and OSE, although some key elements of this 

new process have not been implemented. In the past, FDA has not 

afforded the same focus and attention to postmarket drug safety as it has 

to the drug approval process. For example, an agency official said that, 

unlike for the premarket process, roles and responsibilities for the 

postmarket process have not been clearly defined. Therefore, in January 

2008, the agency began to establish a new framework for drug safety—

which it calls the Safety First Initiative—that is intended to provide this 

structure. Under the initiative, the agency has adopted a multidisciplinary 

approach based on the principles the agency refers to as Equal Voice, 

which are intended to ensure that all necessary parties contribute to 

decision making. In addition, OSE and OND signed a memorandum of 

agreement (MOA) in June 2008 that states FDA’s intent for the two offices 

to contribute equally in determining regulatory actions related to drug 

safety.38 However, in most cases, OND retains the authority to decide 

whether to take regulatory action. According to FDA, OND retains these 

authorities because, for most decisions related to postmarket drug safety, 

OND staff have the broadest expertise in evaluating and managing clinical 

risks and benefits of drugs. 

 

38The MOA expired in June 2009 and a new agreement is in effect through June 2010. FDA 

officials said the agency plans to reevaluate the MOA each year to determine if it is still 

necessary. 

Page 16 GAO-10-68 Postmarket Drug Safety
 

However, as part of the MOA, FDA has transferred authority for one 

regulatory responsibility related to premarket drug safety from OND to 

OSE and plans to transfer authority for two postmarket responsibilities, 

but has not set a time frame for doing so. The MOA describes the agency’s 

intent to transfer to OSE the authority to make final decisions for those 

activities in which the office has expertise. Initially, these include three 

drug safety activities that reside with OND: (1) review of proprietary drug 

names submitted by sponsors, (2) review of protocols and findings of 

observational epidemiologic studies, and (3) review of protocols and 

studies that assess medication error risks. In April 2009, OSE was 

transferred authority for the first regulatory responsibility, the premarket 

review of proprietary drug names, which gives OSE final decision-making 

authority for the activity and allows the office to communicate directly 

with the drug sponsor and issue letters approving or rejecting drug names. 

An OND official said that the transfer of authority for this responsibility 

has been beneficial because proprietary name review was not an area in 

which OND had much expertise. An OSE official said that, since the 

transfer, decisions have been more consistent and the decision letters 

issued to drug sponsors have been more transparent. Agency officials said 

they selected proprietary name reviews as the first authority to transfer to 

OSE because the process is well defined and self contained, and it will 

give OSE experience leading a significant drug safety activity while 

building its expertise to assume authority for the additional 

responsibilities named in the MOA. Officials said the agency intends to 

transfer authority for the two postmarket drug safety responsibilities to 

OSE, but it has not set a time frame for doing so. Agency officials added 

that coordinating some elements of the remaining responsibilities will be 

more complex and OSE still needs to increase its staff to assume these 

additional responsibilities. 

FDA has established multiple opportunities for staff from different 

disciplines to discuss drug safety issues. As part of the MOA, postmarket 

safety issues would be managed by an interdisciplinary team process that 

is similar to FDA’s process for managing drug approvals. FDA issued an 

interim policy describing these safety issue teams in May 2009. Teams 

would be created as needed and include the OSE, OND, and other staff 

necessary to evaluate a given safety issue and make a decision about any 

needed regulatory actions. As part of this process, the teams would 

establish target dates for evaluating the safety issue and later monitor the 

implementation of any regulatory actions. FDA officials said that teams 

have been formed in the past to discuss safety issues, but this new policy 

formalizes existing team-based review practices to provide consistency in 

resolving safety issues. Officials said that they began training staff on the 

Page 17 GAO-10-68 Postmarket Drug Safety
 

new policy in July 2009, but they could not provide an estimate of the 

number of teams that have been formed. In addition, FDA established 

routine joint safety meetings between OND divisions and their OSE 

counterparts. In contrast to the safety issue teams, which are established 

to manage a specific issue, the joint safety meetings focus on broader 

scientific matters and status updates of joint interest to both OND and 

OSE. The agency also continues to hold meetings of its Drug Safety 

Oversight Board. FDA indicated that the board serves as a forum to 

discuss emerging and often controversial drug safety issues. The board 

recently expanded its membership to include representatives from 

additional federal agencies, including the Department of Defense and 

HHS’s Indian Health Service. According to FDA, board members from 

other federal agencies allow FDA to hear perspectives on how its drug 

safety decisions affect federal healthcare systems. 

OSE and OND employees in our small group interviews generally 

identified positive outcomes from FDA’s initiatives, although most OSE 

employees indicated that OND still has more authority in the postmarket 

decision-making process. Many of the OND and OSE employees who 

participated in our small group interviews told us that the more formalized 

process for managing safety issues has helped improve interactions 

between the two offices since our last report. For example, several OSE 

employees said that they now consistently receive a response from OND 

about their consults and recommendations, even if they are not always 

followed, and these reports no longer fall into a “black hole,” as we 

reported in 2006. Employees also described increased communication 

between the two offices, which some said improved tracking of safety 

issues but others said slowed the decision-making process. With regard to 

OSE’s influence in the postmarket decision-making process, 75 percent (39 

of 52) of OND and OSE employees who completed our DCI indicated that 

OSE’s influence has increased since 2006. However, OND and OSE 

employees differed in whether they thought OSE currently serves as an 

equal partner in decision making. Of the OND employees who completed 

our DCI, 64 percent (14 of 22) indicated that OSE now serves as an equal 

partner. In contrast, 57 percent (17 of 30) of OSE employees indicated that 

OND’s perspective still carries more weight, although 60 percent (18 of 30) 

indicated that they thought OSE would serve as an equal partner once the 

new initiatives were fully implemented. 

Despite changes to FDA’s postmarket decision-making process, OND and 

OSE employees report that differences still exist in how the two offices 

view information used to make decisions. For example, one OSE 

employee said that OND staff trust the results of randomized clinical trials 

Page 18 GAO-10-68 Postmarket Drug Safety
 

over the epidemiologic data used by OSE, and another OSE employee said 

that OND is generally more resistant to accepting drug safety 

recommendations based on epidemiologic data. Some OND employees 

also said that physicians are better at identifying the direct clinical impact 

of a drug than other types of staff, such as epidemiologists, who may be 

more skilled in data analysis. OSE is taking steps to address these 

differences. For example, an official said that OSE has provided training to 

OND staff on the methods it uses to do its work. In addition, officials told 

us that OSE plans to increase clinical expertise by hiring additional 

medical reviewers to assist it with the review of adverse event reports. 

FDA Recently 

Implemented Initiatives to 

Facilitate Oversight of 

Postmarket Safety Issues, 

although There Have Been 

Implementation 

Challenges 

FDA implemented both staffing and tracking initiatives intended to 

improve oversight of postmarket drug safety issues. In January 2008, OND 

created two new safety management positions within each of its 17 review 

divisions to reduce variability in how the divisions oversee postmarket 

drug safety.39 In addition to coordinating interactions between the offices, 

employees in these new management positions are to provide leadership 

and to ensure that adequate OND resources and attention are focused on 

safety issues. They also track postmarket safety activities which may 

reduce the burden on individual medical reviewers, who are also 

responsible for reviewing and recommending whether to approve drug 

applications. Several OND medical reviewers indicated during the small 

group interviews that the OND safety management positions have helped 

to track and coordinate management of postmarket safety issues. For 

example, one medical reviewer noted that medical reviewers have 

competing premarket deadlines related to PDUFA and it is helpful to have 

safety staff who do not have these deadlines and can focus on postmarket 

drug safety. 

In addition, OSE reorganized its existing safety project manager positions 

into a single group in October 2006 to oversee the management of safety 

issues across OSE divisions. These safety project manager positions serve 

as OSE counterparts to the OND management positions and are 

responsible for, among other things, coordinating meetings with OND and 

 

39Each OND division now has a Deputy Director for Safety and a Safety Regulatory Project 

Manager; one division has two Safety Regulatory Project Managers. As of July 2009, 3 of the 

17 Deputy Director for Safety positions and 11 of 18 Safety Regulatory Project Manager 

positions were filled in an acting capacity; the remaining positions had permanent staff. 

OND has also created an Associate Director for Safety that has responsibility for 

coordinating the activities of the safety positions across review divisions. 

Page 19 GAO-10-68 Postmarket Drug Safety
 

monitoring OSE activities. These project manager positions were each 

previously assigned to a specific OSE division. An OSE official said this 

reorganization was intended to provide OND staff with a single point of 

contact within OSE, rather than having separate contacts for each OSE 

division. Since the reorganization, the total number of safety project 

manager positions in this group has expanded from 9 to 25. However, 

several OSE employees in our small group interviews cited challenges 

related to their interactions with those holding these OSE safety project 

manager positions. Some said individuals in these positions still seem to 

be learning their new roles and responsibilities. An employee also said that 

turnover among the safety project manager positions has made it difficult 

for the individuals holding those positions to gain experience. As of July 

2009, 20 of the 25 OSE safety project manager positions were filled, but an 

official stated that turnover has been a problem and only one of the 

individuals has been in that position since October 2006. The official said 

that the expansion of responsibilities resulting from the reorganization 

was challenging for some of the individuals and noted that a lack of 

training and clear policies and procedures for these new positions may 

have contributed to the high turnover. The official said OSE is hoping to 

improve retention by implementing training and other support systems for 

these staff. 

FDA is also implementing a new tracking system to assist OSE and OND 

staff in overseeing identified safety issues, although the system has 

limitations. In January 2007, in response to our 2006 recommendation, 

FDA began to incorporate a safety module within its Document Archiving, 

Reporting, and Regulatory Tracking System (DARRTS) to track the 

agency’s management of and response to significant safety issues 

identified with the use of marketed drugs.40 FDA requires that each 

significant safety issue identified by OND and OSE be tracked within 

DARRTS by creating a “tracked safety issue” file. As of July 14, 2009, there 

were 394 active issues. DARRTS is used, among other things, to generate a 

workplan and assign responsibilities for managing these issues, as well as 

to provide updates on the status of these issues. Officials told us that while 

the system contains documents describing specific recommendations and 

safety actions, it does not, as we recommended, allow FDA to 

systematically track how issues were resolved and whether OSE’s 

 

40DARRTS is intended to help CDER staff manage the drug review process by serving as a 

central repository for information and allowing staff to upload communications and other 

documentation, generate reports, and create status updates. The agency is releasing 

DARRTS in stages. The first version was released in January 2006. 

Page 20 GAO-10-68 Postmarket Drug Safety
 

recommendations were implemented. For example, an FDA official told us 

that DARRTS cannot provide the agency with a summary of the 

recommendations for safety actions that OSE has made to OND or how 

the safety issues were ultimately resolved. FDA indicated that, due to 

limited resources, it does not plan to incorporate this capability into 

DARRTS in the next year or two. In addition, FDA has identified certain 

limitations with the system, such as problems of completeness and 

accuracy and the need for a mechanism to notify relevant staff when a 

new tracked safety issue is created. According to FDA, some of the 

identified problems have been corrected while others will be addressed at 

a later date. An official said that the agency expects that future problems 

will be minimized by improved preimplementation testing. For example, 

the official noted that the July 2009 update of DARRTS, which allows the 

system to be used for monitoring both postmarket studies and risk 

management plans, was more rigorously tested by users prior to its 

implementation. 

FDA is also utilizing contractors to improve oversight of specific new 

authorities created by FDAAA. We and others have identified problems in 

the agency’s tracking of required and requested postmarketing studies, 

such as OND reviewers not meeting their goals for reviewing in a timely 

manner the annual status reports submitted by drug sponsors.41 In 2008, 

FDA hired a contractor to monitor and provide support for postmarketing 

studies, including the review of these annual status reports.42 FDA officials 

said that this contract has been very productive because it allows the 

review of the annual status reports to be completed, which is very time 

consuming, while allowing the agency to move ahead in its oversight of the 

new postmarketing studies it is requiring under its FDAAA authority. The 

 

41GAO, New Drug Approval: FDA Needs to Enhance Its Oversight of Drugs Approved on 

the Basis of Surrogate Endpoints, GAO-09-866 (Washington, D.C.: Sept. 23, 2009). See 

also, Booz Allen Hamilton, Postmarketing Commitments Study Final Report, a report 

prepared at the request of FDA, January 2008, http://www.fda.gov/ForIndustry/ 

UserFees/Prescription DrugUserFee/ucm119856.htm (accessed July 23, 2009). 

42The contractor is annually reviewing the annual status reports associated with 

postmarketing studies that were requested prior to the enactment of FDAAA—what the 

agency defines as its “backlog.” The review of these reports is required by FDAAA. Pub. L. 

No. 110-85, § 921, 121 Stat. 823, 962 (codified at 21 U.S.C. § 355(k)(5)). The contractor is 

also reviewing the annual reports submitted by drug sponsors for those postmarket studies 

that have been required or requested since FDAAA. See, for example, Booz Allen Hamilton, 

Deliverable 2-8: Final Report on the PMR/PMC Backlog Review, a report prepared at the 

request of FDA, April 10, 2009, http://www.fda.gov/Drugs/GuidanceComplianceRegulatory

Information/Post-marketingPhaseIVCommitments/ucm180982.htm (accessed Oct. 20, 

2009). 

Page 21 GAO-10-68 Postmarket Drug Safety
 

agency is also hiring a contractor to help oversee the required risk 

management plans. 

FDA Is Revising Its 

Program for Resolving 

Scientific Disputes but the 

Changes Have Not 

Sufficiently Addressed the 

Independence of the 

Process 

FDA is revising CDER’s program for resolving scientific disputes raised by 

individual employees, but the changes do not sufficiently address our prior 

recommendation for improving the independence of the process. 

Beginning in 2007, FDA conducted a review of each of its centers’ dispute 

resolution processes, including CDER’s DPO program.43 As a result of this 

review, FDA developed a list of mandatory elements for all centers to 

implement during fiscal year 2008 and a list of voluntary best practices for 

scientific dispute resolution activities. For example, FDA now requires 

that employees of each center who file a DPO have the option to appeal to 

FDA’s Office of the Commissioner for a review to determine if the center 

followed its own dispute resolution process correctly.44 CDER indicated 

that its DPO policy is being revised to reflect this “process review” and 

other new agencywide requirements, but noted that CDER plans to make 

few other changes. As of October 2009, the revised policy had not been 

finalized. 

While CDER continues to make changes to its DPO policy, the planned 

changes do not address a weakness we identified in our 2006 report—that 

the program it established to resolve scientific disputes may not be viewed 

as independent as a result of the CDER Director’s extensive involvement. 

According to a July 2009 draft of the revised policy, as was the case in 

2006, the Ombudsman, whom the policy designates as the focal point for 

overseeing the resolution of disputes, would consult with the CDER 

Director before deciding whether a dispute warrants review. An agency 

official told us that this consultation is important because the Ombudsman 

does not have the same scientific expertise as the CDER Director. The 

official acknowledged that, while the Ombudsman is included as a way to 

improve the independence of the DPO program, this position does not 

meet the standards of independence established by the Coalition of 

 

43FDA has five centers: CDER, the Center for Biologics Evaluation and Research, the 

Center for Devices and Radiological Health, the Center for Food Safety and Applied 

Nutrition, and the Center for Veterinary Medicine. 

44The process review would also include an assessment of whether the center considered 

all relevant evidence bearing on the scientific question at issue and whether the initiator of 

the dispute was provided an opportunity to express his or her concerns at all appropriate 

levels. As examples of other requirements, FDA requires center dispute resolution policies 

to include antiretaliation language and an ‘opt-up’ to the center director if a dispute is of 

sufficient immediacy and scale of impact to public health. 

Page 22 GAO-10-68 Postmarket Drug Safety
 

Federal Ombudsmen.45 In addition, according to the draft DPO policy, the 

CDER Director would still appoint the chair of the ad hoc review panel 

and decide how the dispute should be resolved, in consideration of the 

panel’s recommendation. The draft DPO policy includes the required 

option of a process review by the Office of the Commissioner, which 

would not involve the center director or other center staff in decision 

making. However, this review is limited to determining whether CDER 

followed its own processes correctly, and it does not consider the 

scientific merits of the dispute. As a result, CDER’s revised DPO program 

still may not be viewed as sufficiently independent for resolving disputes. 

As of July 2009, CDER’s DPO program had not been used to resolve a 

difference of opinion. The Ombudsman attributed the lack of use to the 

CDER Ombudsman’s Office’s management of disputes so that they never 

reach the level of a formal DPO.46 FDA also indicated that the DPO 

program is narrowly focused on individual disagreements that employees 

have been unable to resolve within their supervisory chain; if agreement 

has not been reached between scientific disciplines, the principles of 

Equal Voice are intended to help different disciplines express differences 

of opinion. OND and OSE employees who completed our DCI reported a 

variety of reasons for why they chose not to file a formal DPO. Of the 52 

OND and OSE employees who completed our DCI, 36 indicated that they 

had not had a difference of opinion that would have qualified for filing a 

dispute. However, 13 of the employees did report having a difference of 

opinion where they thought that FDA’s action or lack of action had the 

potential to have a significant negative impact on public health.47 When 

asked why they did not use CDER’s program to resolve this difference, 

these employees most frequently indicated that they preferred to express 

 

45The standards state that several factors are important to assessing independence, such as 

whether anyone affected by the ombudsman’s actions can control or limit the 

ombudsman’s performance or reduce the ombudsman’s budget or resources. Coalition of 

Federal Ombudsmen (CFO) and Federal Interagency ADR Working Group Steering 

Committee, A Guide For Federal Employee Ombuds: A Supplement to and Annotation of 

the Standards For The Establishment And Operations Of Ombuds Offices Issued By The 

American Bar Association, May 9, 2006, http://www.adr.gov/pdf/final_ombuds.pdf, 

(accessed July 27, 2009).

46An agency official told us that CDER asked staff in 2007 for input on why the program had 

not been used, but only a few staff responded. The official said that CDER interpreted the 

low response rate to mean that staff did not feel strongly about the program, so, at that 

time, no changes were made to the program. 

47The remaining 3 employees out of the 52 who completed the DCI indicated that they had 

no opinion about the issue (2) or did not provide an answer (1). 

Page 23 GAO-10-68 Postmarket Drug Safety
 

the opinion in written documentation (7) or were not aware of the 

program (6).48 In addition, 3 of these 13 employees noted concerns about 

the fairness of the DPO program as one reason for why they did not utilize 

it. None of the 13 employees indicated that they preferred the option of 

discussing the differing opinion informally with the Ombudsman.49

FDA plans to improve its identification of drug safety issues by developing 

new adverse event systems to collect and store adverse event reports and 

by increasing access to external sources of data. However, the adverse 

event systems and a new network of external data providers have not yet 

been implemented. 

FDA Plans to 

Implement New 

Adverse Event 

Systems and Is 

Increasing Access to 

External Sources of 

Drug Safety Data 

FDA Is Developing New 

Systems to Improve 

Collection and Analysis of 

Drug Adverse Event 

Reports, but 

Implementation Is Not 

Expected Until 2010 

FDA is developing two new adverse event systems to help it identify drug 

safety problems—one to improve the collection and processing of adverse 

event reports and another to store reports and provide FDA staff with 

improved tools for analyzing them. FDA’s complete adverse event system 

for human drugs will not be implemented until the end of 2010. 

The new adverse event report collection and processing system, 

MedWatchPlus, is intended to increase the accuracy and timeliness of 

reports accessible to FDA staff and is scheduled to be implemented for 

human drugs by summer 2010.50 The current MedWatch Web site collects 

Adverse Event Collection and 

Processing 

 

48Under 21 C.F.R. § 10.70, an agency employee working on a matter may record individual 

views on that matter in a written memorandum, which is to be placed in the file. 

49Employees completing the DCI were able to select more than one reason why they did not 

use CDER’s program to resolve differences of opinion. 

50MedWatchPlus will be implemented in stages. The first version is scheduled to be 

complete by fall 2009, but will only be able to accept adverse event reports for food and 

veterinary drugs. In spring 2011, FDA plans to release a version that will be able to accept 

adverse event reports for medical devices and other remaining products. 

Page 24 GAO-10-68 Postmarket Drug Safety
 

adverse event reports about prescription drugs by providing forms that 

patients and healthcare providers can submit online or download and send 

to FDA in paper form.51 Drug manufacturers may also use this system to 

download forms, although they may elect to submit electronically through 

an alternative system, the Electronic Submissions Gateway (ESG).52

Although reports submitted through ESG go directly into CDER’s database 

of adverse events, AERS, paper reports, and reports submitted using the 

MedWatch online form must be processed and manually entered into 

AERS before they are available to FDA staff. FDA estimates that reports 

submitted on paper may take from 2 weeks to 2 months from the time of 

receipt to be entered into AERS where they can be analyzed by FDA staff. 

The new MedWatchPlus system will allow online reports to be processed 

automatically and transferred directly into the agency’s adverse event 

system,53 reducing the need to process and enter reports manually. 

According to FDA, automatic processing will cut down on errors related to 

data entry and should allow for more timely availability of reports for 

analysis. FDA estimates that electronic submissions are generally available 

in AERS within 2 days of their receipt. 

FDA expects that MedWatchPlus will enable the agency to increase the 

electronic submission rate of reports, increase the number of reports 

accessible to FDA staff for analysis, and improve report quality. In fiscal 

year 2008, 61 percent of reports from manufacturers were submitted 

electronically. In August 2009, FDA issued notice of a proposed rule that 

would require manufacturers to submit adverse event reports 

electronically,54 which would mean that manufacturers who do not 

currently submit reports electronically would either use ESG or would 

 

51FDA also provides a toll-free telephone number that can be used to submit adverse event 

reports. 

52ESG is an FDA system that enables the electronic submission of regulatory information, 

such as adverse event reports, for review. Manufacturers that choose not to utilize ESG 

must submit paper forms, which may be obtained through MedWatch. 

53MedWatchPlus will process each report by assigning a unique identifier, translating the 

report into accepted medical terminology using standard medical dictionaries, prioritizing 

the report based on factors such as the seriousness of the adverse event, and routing the 

report to the correct center within FDA. 

54See 74 Fed. Reg. 42,184 (Aug. 21, 2009). This proposed rule amends previous requirements 

for the submission of postmarket safety reports, see 21 C.F.R. §§ 310.305, 314.80, 314.98, 

and 600.80 (2009). The rule will be available for comment until November 19, 2009, after 

which FDA may issue the final rule. FDA has proposed that the new requirements would go 

into effect 1 year after the publication of the final rule. 

Page 25 GAO-10-68 Postmarket Drug Safety
 

need to use the MedWatchPlus online form.55 Increasing the electronic 

submission rate should allow for more reports to be available to FDA staff. 

Currently, FDA does not routinely enter all paper reports from 

manufacturers into AERS,56 which an official said is because of the cost to 

the agency. However, all reports from manufacturers submitted 

electronically through MedWatchPlus will be automatically entered into 

AERS, which should reduce costs and allow for more reports to be 

available for analysis.57 FDA also expects to increase the number of 

electronic submissions from patients and healthcare providers by making 

the system easier to use. As part of MedWatchPlus, FDA will use an 

interactive questionnaire that will guide submitters through a series of 

questions, which FDA expects will increase the accuracy and 

completeness of reports. For example, submitter errors, such as 

inaccurate drug names, create a burden for FDA.58 Through 

MedWatchPlus, the submitter will be provided with a menu of choices for 

the name of the drug. The questionnaire will also audit the information 

received and prompt for missing information. 

 

55According to FDA, it is mostly larger manufacturers that have invested in the data 

exchange systems needed to use ESG. The agency expects that MedWatchPlus will provide 

smaller manufacturers with a more cost effective means of reporting adverse events 

electronically. 

56FDA enters all adverse event reports sent directly to it from patients and healthcare 

providers. The agency also enters all electronic reports from manufacturers, as well as all 

paper reports from manufacturers concerning new molecular entities for the first 3 years 

after approval. New molecular entities are potentially innovative drugs containing active 

chemical substances that have never been approved for marketing in the United States in 

any form. For all other paper reports from manufacturers, FDA only enters reports for 

serious adverse events. In fiscal year 2008, 93,085 paper reports from manufacturers of 

adverse events not classified as serious, which comprised almost 18 percent of all reports 

received by FDA, were not entered into AERS. 

57According to FDA, paper reports cost approximately $35 per report to process, whereas 

electronic submissions cost approximately $12 per report to process. 

58In a 2008 report, IOM noted that submitters may use multiple different names for the same 

drug due to the use of the trade name rather than the generic name, inclusion of dosage 

information in the drug name, or misspellings. IOM reported that a manual review of the 

AERS database identified 300,000 different drug names that reviewers determined actually 

represented only about 3,000 standard generic names. S. Robinson, R. Pool, and R. Giffin, 

Institute of Medicine of the National Academies, Forum on Drug Discovery, Development, 

and Translation, Emerging Safety Science: Workshop Summary (Washington, D.C.: 

National Academies Press, Apr. 9, 2008). 

Page 26 GAO-10-68 Postmarket Drug Safety
 

FDA is also developing a new database to store adverse event reports once 

they have been submitted that should offer integrated data analysis 

features to facilitate the identification of safety issues. The new database, 

the FDA Adverse Event Reporting System (FAERS), is expected to receive 

reports from MedWatchPlus and other FDA applications for all FDAregulated products and store them in a single location.59 In addition to 

avoiding redundancy among the center databases, FDA has stated that a 

consolidated database would benefit drug safety, for example, by 

facilitating the sharing of adverse event reports across centers for 

combination products.60 FAERS will replace AERS and is intended to 

address some current AERS limitations that affect how OSE staff do their 

work. FDA officials told us that OSE staff view the current version of 

AERS as a giant “filing cabinet,” which lacks integrated software for data 

mining and signal management that could help them to monitor drug 

safety more effectively.61 FDA officials said that, currently, to use the 

software, staff have to periodically extract the data from AERS and 

transfer them to another system for analysis, which means that analyses 

cannot be conducted in real time. In contrast, FDA plans to include 

integrated signal management and data mining software in FAERS, which 

will make these features easier to use and allow for analyses of safety 

signals closer to real time. 

Adverse Event Storage and 

Analysis 

FDA officials said that the agency plans to address other adverse event 

report quality problems by including new features in FAERS. For example, 

an adverse event reviewer told us that AERS lacks a dedicated data field 

(such as a checkbox) to indicate whether a female patient described in an 

adverse event report is pregnant. As a result, reviewers must manually 

review the narrative of reports for women aged 15 to 45 to determine 

whether the patient was pregnant. FDA officials said that FDA plans to 

include a dedicated data field to indicate whether a report identified the 

patient as pregnant in FAERS. An adverse event reviewer also identified 

the lack of a link between an adverse event report and FDA-approved label 

 

59Currently, FDA maintains multiple databases for storing adverse event data. For example, 

AERS is used by CDER to store drug reports, while another center uses a separate 

database to store medical device reports. 

60Combination products are comprised of two or more regulated components, for example, 

a drug-device combination product. According to FDA, sharing information about such 

products is currently difficult to do in a timely manner. 

61Data mining software allows OSE staff to more easily identify patterns in the reports to 

find new safety signals. Signal management software allows OSE staff to monitor safety 

signals over time and create alerts. 

Page 27 GAO-10-68 Postmarket Drug Safety
 

information as a problem because it hinders staff in determining whether 

the adverse event is new or has already been identified and included in the 

drug’s label. FDA officials said that linkage to label information is a goal 

for inclusion in FAERS, but it is complex and the agency does not have a 

time frame for its inclusion. 

FAERS development has experienced delays, but FDA expects that it will 

be partially implemented by the end of 2010. FDA began developing an 

update to AERS in 2004. However, according to a 2006 report by an FDA 

contractor, deficiencies in FDA’s procurement practices and the agency’s 

decision to expand the project’s scope to develop an agencywide database 

for all FDA-regulated products resulted in delays.62 The contractor 

reported that these obstacles in development resulted in a 4- to 5-year 

delay and an estimated $25 million in additional development costs. 

Currently, FDA indicated that it is prioritizing FAERS requirements to 

determine what features and capabilities are possible for the first version 

of FAERS. FDA plans to complete the first version of FAERS, for drugs 

and biologics, by the end of 2010. However, this version will not include 

fully integrated data mining and signal management software. FDA does 

not have an estimated time frame for when these features will be fully 

integrated. 

FDA Increased Funding for 

External Data Acquisition 

and Is Beginning to Access 

Data from Federal Sources 

FDA increased funding for acquiring the external data that it uses to 

examine drug safety issues from about $5 million in fiscal year 2007, to 

about $28 million in fiscal year 2008.63 FDA recently added additional 

funds to existing contracts with four private companies that conduct drug 

safety studies using their own databases of electronic health information. 

Since FDA initially awarded about $5.4 million in total to these compani

in fiscal year 2005, these contracts have yielded five complete

epidemiologic studies on drug safety, including a study on how 

antidepressant use in pregnancy affects the health of newborns. In fiscal 

year 2008, FDA added about $9 million in total to the four contracts. 

However, FDA officials said that under the current contracts it is difficult 

to expand funding in response to the agency’s needs and they will be 

es 

d 

 

62Breckenridge Institute, Independent Verification and Validation of AERS II 

Requirements Process (Breckenridge, Colo.: 2006). 

63Most of the increase, about $22 million, came from user fee funding resulting from the 

reauthorization of PDUFA. 

Page 28 GAO-10-68 Postmarket Drug Safety
 

changing to a different contract type when these contracts end in 2010.64

They said the new contract type will make it easier to add funds as the 

need arises for additional epidemiologic studies to examine previously 

unknown drug safety issues. 

FDA has also used the increased data acquisition funds for contracts with 

private companies that allow FDA staff direct access to data that can be 

used to conduct drug safety studies internally. These contracts provide the 

agency with access to drug utilization data, which are useful to FDA for, 

among other things, providing an estimate of how many people have been 

exposed to a drug, which provides context for adverse event analyses. 

These contracts allow FDA to download the data onto the agency’s servers 

where staff can access the data to conduct drug safety studies. In 2008, 

FDA awarded contracts valued collectively at over $14 million for a base 

year and 3 option years.65 The three new contracts replaced an existing 

contract with a single vendor and, according to an FDA official, represent 

an approximate tripling of funding for access to drug utilization data. The 

official also said that contracts with three vendors allow shortcomings in 

one data set to be compensated by information from another. For 

example, one contractor has mail order pharmacy claims data, which are 

not available from the other two contractors. 

In addition to funding contracts with private companies, FDA is in the 

early stages of forming partnerships with the Department of Veterans 

Affairs (VA), the Department of Defense (DOD), and the Centers for 

Medicare & Medicaid Services (CMS) to access their databases of 

electronic health information for drug safety research. FDA signed 

memoranda of understanding with VA and DOD in 2007 to enable these 

agencies to share information necessary to evaluate drug safety with FDA. 

FDA allocated about $3.6 million to fund these agreements in 2008, which 

among other things, provided funding for research projects, such as a 

study of the relationship between the use of smoking cessation drugs and 

suicidal behavior, and funding for staff to support such studies.66 In 

 

64The new contracts will be indefinite delivery contracts, which do not procure or specify a 

firm quantity of services (other than a minimum or maximum quantity) and which provide 

for the issuance of orders for the performance of tasks during the period of the contract. 

65FDA officials explained that the contracts are structured with multiple option years so 

that FDA has adequate time to learn to use the databases, but can choose to switch vendors 

as new technologies emerge. 

66FDA allocated an additional $4.3 million for VA and DOD in fiscal year 2009. 

Page 29 GAO-10-68 Postmarket Drug Safety
 

addition, FDA signed an interagency agreement with CMS in August 2008 

to access both Medicaid and Medicare data. As part of this agreement, 

FDA transferred $1 million to CMS in part to fund a project to create a 

Medicaid database amenable to research on drug safety.67 FDA is also 

working on several pilot projects using Medicare prescription drug data. 

These data on Medicare beneficiaries provide the agency with access to 

new information on the elderly and disabled—groups that are generally 

underrepresented in traditional clinical trials that FDA uses to assess 

safety prior to approval. FDA officials said that partnering with federal 

agencies is beneficial because they have large databases of electronic 

health information that may be accessed more cheaply than contracting 

with private entities. 

FDA Is in the Early Stages 

of Developing a Network 

of External Data Providers 

Intended to Enhance Its 

Drug Safety Surveillance 

FDA is also taking steps to improve identification of safety issues by 

creating a network of external drug safety data providers, but the agency 

is in the early stages of developing it. The FDAAA-mandated surveillance 

system, known as the Sentinel System, will be a network of databases of 

electronic health information that can be utilized for safety signal 

evaluation for drugs and other marketed medical products. FDA officials 

said one of the purposes of the Sentinel System will be to provide the 

agency with an active surveillance tool that will be capable of generating 

safety signals that are not identifiable through AERS. For example, AERS 

relies on patients and doctors to submit adverse event reports, but if they 

do not recognize an event as being potentially drug-related, they may not 

file an adverse event report. In addition, FDA expects that the Sentinel 

System will build on the current data contracts the agency uses to conduct 

formal epidemiologic studies, which are generally used to confirm safety 

signals after they have been identified, by allowing researchers to specify 

potential safety problems in advance and monitor for these problems in 

near real time. The Sentinel System is in the early stages of development 

and as of June 2009 there were no established milestones.68 Thus far, FDA 

 

67Currently, each state Medicaid program stores its data files in separate state databases, 

which makes it difficult to conduct drug safety studies. This project will combine these 

databases into a single, unified Medicaid database. An FDA official said the agency planned 

to continue funding this project in 2009 and has allocated an additional $1 million. 

68In June 2009, we recommended that FDA develop a plan for completing Sentinel, 

including the establishment of milestones. We also recommended that FDA implement 

appropriate security and privacy safeguards as Sentinel is developed. GAO, Privacy and 

Security: Food and Drug Administration Faces Challenges in Establishing Protections 

for Its Postmarket Risk Analysis System, GAO-09-355 (Washington, D.C.: June 1, 2009). 

Page 30 GAO-10-68 Postmarket Drug Safety
 

has established a senior management team, conducted a series of meetings 

with stakeholders, and created a working group of federal agencies that 

are developing complimentary initiatives. FDA officials said they have not 

finalized funding or staffing plans for the system. In addition, many other 

key decisions have yet to be made, including: sources of data, an 

information technology infrastructure, and methods of analysis. In 2008, 

FDA awarded eight contracts to investigate these and other issues. Seven 

of the reports from these contracts have been completed and FDA expects 

that the remaining report will be completed by the end of 2009. 

FDA’s workload related to postmarket drug safety has increased as a 

result of new authorities and other factors. While the agency received 

increased funding and is hiring staff to conduct postmarket drug safety 

activities, it faces difficulties in recruiting the additional staff and external 

experts needed to meet its increasing responsibilities. 

Although Staff Has 

Recently Increased, 

FDA Faces 

Challenges Meeting 

Its Expanding 

Postmarket Safety 

Workload 

FDA Reports That New 

Postmarket Drug Safety 

Responsibilities Have 

Increased Its Workload 

and That It Is Challenged 

by Competing Priorities 

FDA reports that new postmarket drug safety responsibilities and other 

factors have led to an increased workload for which FDA has identified a 

need for increased staff.69 Of the OSE and OND staff that completed our 

DCI, 77 percent (40 of 52) indicated that their workload had increased or 

greatly increased since 2006. In addition, 60 percent (31 of 52) of the 

employees said that they either were not able to meet their postmarket 

drug safety responsibilities during an average workweek or were only able 

to meet these responsibilities by working overtime. Many employees told 

us during our small group interviews that one source of this increased 

workload has been the new postmarket drug safety responsibilities added 

by FDAAA. FDA officials said that requiring a drug sponsor to conduct 

 

69Similarly, in June 2009, we reported that FDA’s workload had grown due to an increase in 

the agency’s statutory responsibilities and a growing number of medical products subject 

to FDA oversight. We also reported that an increased reliance on user fee funding has 

limited the agency’s ability to fulfill its oversight responsibilities in some other areas. GAO, 

Food and Drug Administration: FDA Faces Challenges Meeting Its Growing Medical 

Product Responsibilities and Should Develop Complete Estimates of Its Resource Needs, 

GAO-09-581 (Washington, D.C.: June 19, 2009). 

Page 31 GAO-10-68 Postmarket Drug Safety
 

postmarketing studies is more time consuming for FDA staff than the past 

process of requesting such studies. For example, to require a study, 

officials said the agency needs to document its rationale in a legally 

enforceable contract with a sponsor that may describe specific elements 

of the study design. The agency also works with sponsors to establish 

milestones for the completion of these studies. In addition, officials said 

the process of overseeing the development and implementation of a drug 

sponsor’s required risk management plan has led to additional meetings 

between OND and OSE, as well as additional interactions with drug 

sponsors to review the proposal and discuss even minor modifications to 

it. FDA officials said that the new FDAAA authorities are especially time 

consuming because the agency is still developing processes for how to 

conduct this new work. Officials said that proposals for requiring 

postmarketing studies and REMS are being reviewed by others within FDA 

to ensure consistency in the application of the authorities. FDA officials 

expect that some of this additional workload will decrease as the process 

becomes more routine. 

OND medical reviewers described challenges meeting their premarket and 

postmarket responsibilities. Several reviewers noted that their primary 

focus is on completing premarket work within PDUFA time frames, and 

issues related to postmarket safety receive lesser priority. Two medical 

reviewers said that important identified safety issues would take priority 

over meeting PDUFA deadlines, but other reviewers told us that their 

workload prevents them from conducting reviews that would allow them 

to identify new postmarket safety issues. For example, reviewers said they 

are unable to fully review the Periodic Safety Update Reports submitted by 

drug sponsors, which are comprehensive reports containing information 

on serious and nonserious adverse events.70 According to some OND 

reviewers, medical reviewers do not have the time to fully analyze these 

 

70FDA defines adverse events as serious when they result in death, are life-threatening, 

require inpatient hospitalization or prolongation of hospitalization, cause significant 

disability/incapacity, or cause a birth defect. Other events may also qualify as serious if 

they require medical or surgical intervention to prevent one of these outcomes from 

occurring. See 21 C.F.R. § 314.80(a) (2009). FDA defines nonserious adverse events as any 

events that do not qualify as serious. However, an FDA medical reviewer advised us that 

events categorized as nonserious may include events that would constitute an important 

safety signal. For example, the reviewer said that a medical event that is significant enough 

to send a patient to the emergency room may not be considered serious in the regulatory 

sense, if the patient is treated and released without being admitted to the hospital. FDA 

officials said that, as a result, staff need to consider both serious and nonserious adverse 

event reports when monitoring the safety of drugs. 

Page 32 GAO-10-68 Postmarket Drug Safety
 

reports to look for potential safety issues.71 OSE staff told us that 

workload demands prevent them from reviewing these reports. G

nonserious adverse events may not be entered into AERS, failure to fully 

review Periodic Safety Update Reports may result in FDA missing safety 

signals for nonserious adverse events. 

iven that 

 

OSE also reported that competing demands impact its ability to meet its 

postmarket responsibilities, such as its new premarket responsibilities for 

reviewing proposed proprietary drug names within PDUFA deadlines and 

communicating its decisions to drug sponsors. The staff involved in these 

reviews estimated that approximately 90 percent of their time is spent on 

such premarket activities, which leaves little time to spend on their other 

postmarket drug safety responsibilities, such as analyzing reports of 

medication errors. For example, an FDA employee told us that they do 

monitor AERS to identify safety signals, but they do not have time to 

complete follow-up reviews of these signals. Although employees agreed 

that the most important safety issues do get resolved, one employee said 

that follow-up reviews are often lower priority than fulfilling premarket 

responsibilities.72 In addition, other OSE staff identified competing 

demands that hampered their ability to conduct postmarket safety work. 

For example, OSE adverse event reviewers told us that consult requests 

from OND consumed the majority of their time, leaving them less time to 

conduct self-initiated safety analyses of adverse event data. According to 

FDA, each OSE adverse event reviewer receives an average of about 44 

adverse events reports per day,73 and reviewers told us that given 

competing priorities, they are not able to review them all. 

A contractor reviewing OSE’s increasing workload found that additional 

staff will be needed in order to fulfill the new responsibilities related to 

FDAAA and the MOA. According to the contractor’s December 2008 

71OND is officially responsible for reviewing these reports. OND medical reviewers 

described several other challenges that impeded their review, including a lack of sufficient 

epidemiologic expertise and available guidance. They also said that these reports are of 

poor quality and do not provide the total numbers of adverse events reported by the 

sponsor since the drug was approved, which limits their usefulness in identifying potential 

trends in the data. 

72One employee said that there are safety issues identified in 2006 for which they still have 

not been able to complete follow-up reviews. 

73Adverse event reviewers told us that the number of reports they receive varies 

considerably based on the drugs in each adverse event reviewer’s portfolio, and can be as 

high as 200 reports per day. 

Page 33 GAO-10-68 Postmarket Drug Safety
 

report, OSE would need an estimated total of 453 full-time equivalent 

employees by 2011 to meet its increased workload, more than double 

OSE’s current staffing.74 While the contractor identified workload 

increases throughout OSE, it found that the greatest increases would be 

related to the review of risk management plans and postmarket safety 

data, such as adverse events. 

FDA Has Hired Some New 

Staff, but May Face 

Obstacles Recruiting 

Additional Staff to Manage 

Its Increased Workload 

OSE and OND officials described fiscal year 2008 as a very successful 

hiring year, due in part to specific hiring initiatives. FDA indicated that 

since the start of fiscal year 2008, OND increased its staff from 736 to 928 

and OSE increased its staff from 114 to 193.75 The staff hired included OND 

medical reviewers who conduct premarket and postmarket reviews and 

OSE staff with postmarket drug safety responsibilities, such as 

epidemiologists and risk management experts. Agency officials attributed 

this success to specific hiring initiatives. For example, officials told us that 

both OSE and OND used a summer 2008 job fair and direct-hire authority 

to hire staff more quickly.76 While the agency has had direct-hire authority 

for medical reviewers since 2003, FDA indicated that it temporarily 

obtained direct-hire authority from April 2008 through September 2008 for 

epidemiologists. The OSE and OND Directors said that they hired 

candidates within weeks under the authority, rather than the 3 to 6 months 

it can typically take to announce positions, screen applications, conduct 

interviews, and hire individuals. The OSE Director told us that without the 

authority, interested candidates have sometimes accepted employment 

 

74Leadership Performance Solutions, Office of Surveillance and Epidemiology Workload 

Analysis Report, a report prepared at the request of FDA (Silver Spring, Md.: December 

2008). The contractor acknowledged that its estimates were not statistically valid because 

it used agency estimates to analyze OSE’s future workload. The contractor noted that OSE 

did not have a consistent, systematic process for collecting workload data and 

recommended that the office implement an ongoing process for estimating staffing needs. 

In a 2009 report, we also found that FDA lacks reliable data on workload and 

accomplishments, and we recommended that FDA develop an evidence-based estimate of 

the resources need to fulfill all of its responsibilities. GAO-09-581. 

75FDA provided staff counts as of September 22, 2009. According to FDA officials, the fiscal 

year 2009 staffing ceiling for OND was 930, while for OSE it was 211. 

76Direct-hire authority, given by the Office of Personnel Management, allows agencies to 

expedite the hiring of qualified applicants for critically needed positions by eliminating the 

need to comply with certain elements of the federal hiring process. See 5 C.F.R. §§ 337.201-

337.206 (2009). 

Page 34 GAO-10-68 Postmarket Drug Safety
 

offers elsewhere before FDA could extend its own offer.77 In addition, an 

official said that CDER’s ability to offer hiring bonuses, relocation 

reimbursement, and student loan repayment contributed to its hiring 

success during fiscal year 2008.78

Although OSE significantly increased its staff in fiscal year 2008, hiring and 

staffing challenges could make it difficult for the office to meet the 

workload generated by its new postmarket drug safety responsibilities. 

While the contractor estimated that OSE would need 453 full-time 

equivalent employees by 2011, the OSE Director did not know if the 

agency planned to increase OSE’s fiscal year 2009 staff ceiling of 211 in 

fiscal year 2010. However, officials said that recruiting the right people 

with the desired drug safety expertise is difficult. For example, an OSE 

official said that it is hard to find candidates who have experience with the 

specific epidemiologic activities conducted by FDA, and the agency 

therefore looks for candidates with epidemiologic skills who can then be 

trained by the agency once they are hired. Officials indicated that while 

the new hires can bring up-to-date skills, their lack of experience means 

that it can take up to 3 years before newly hired employees can work 

independently. In addition, an official said it is difficult for OSE to 

compete with drug companies, who can offer higher compensation, for the 

same pool of talent. Given the estimated workload increases identified in 

the FDA contractor’s December 2008 review, OSE may be challenged to 

hire staff quickly enough to meet its increasing workload. 

FDA Faces Technological 

and Staffing Challenges 

That Limit Its Capacity to 

Conduct a Growing 

Number of Postmarket 

Safety Studies 

FDA officials said that they lack adequate computational capacity and 

enough staff to make full use of external sources of data for drug safety 

studies, and FDA expects the number of such studies to grow. OSE has 

increased funding for acquiring external data and a recent workload 

planning report prepared by an FDA contractor indicates that OSE intends 

to triple the number of epidemiological studies it conducts using such data 

from 13 in 2008 to 39 in 2011. An OSE official told us that currently, most 

of the epidemiologic studies are conducted by contractors, but that OSE 

would like to conduct more studies internally. The official said that 

internal studies afford FDA more control over the analyses, as well as 

 

77According to FDA, the agency no longer plans to request new direct-hire authority for 

epidemiologists from the Office of Personnel Management. 

78The official said the incentives it offered new hires were made available by FDA from 

savings realized from unfilled vacancies. These incentives are no longer available. 

Page 35 GAO-10-68 Postmarket Drug Safety
 

provide increased professional opportunities to OSE staff, which may lead 

to greater staff retention. However, the official said that conducting more 

internal studies would require greater computational capacity and more 

staff.79 OSE officials told us, for example, that the current technological 

infrastructure limits staff to running a single analysis at a time and that the 

computer servers in CDER “routinely crash” when dealing with large data 

sets. OSE officials also said that they lack programmers who are needed to 

extract data from databases and prepare data sets for analysis. OSE 

officials said that the office has faced difficulties hiring programmers 

because the position descriptions that it would use to hire these 

programmers are currently only available to the agency’s Office of 

Information Management, which has meant that such staff may not be 

hired by OSE.80 They indicated that, without enough programmers, this 

work is shifted to epidemiologists, who must then spend more time on 

each study and have less time to devote to developing and carrying out 

additional studies. 

CDER is developing a computational science center that is intended to 

address some of these challenges, but this center is in the early stages of 

development. FDA indicated that the center is intended to support both 

pre- and postmarket quantitative analyses of the safety, efficacy, and 

quality of drugs.81 FDA officials said it should address current problems by 

providing increased computational capacity and more staff, including 

programmers and data managers that can be utilized by OSE. However, 

they said that the center is currently in the developmental stages, and that 

there is no time frame for its completion.82 In the interim, OSE is using 

short-term fixes, such as increasing the memory capacity of existing 

servers. OSE officials noted that OSE may also contract out some 

 

79According to FDA, studies completed by external contractors also consume agency 

resources. An FDA official said that each external epidemiologic study conducted by a 

contractor should have an OSE lead epidemiologist assigned to it to help plan the study, as 

well as a programmer to extract the data from the contractor’s database. 

80Agency officials said that OSE could still hire staff with programming expertise under the 

office’s existing position descriptions. While OSE officials said that they have managed to 

hire an employee with programming expertise to support ongoing drug safety studies under 

the epidemiologist position description, they said that it is extremely rare to find a 

programmer who meets all of the qualification requirements for an epidemiologist position. 

81According to FDA, the center will be a virtual organization that draws on expertise from 

across CDER and it will not be housed in a single location or set of offices. 

82According to FDA, a contractor has developed a strategic plan for the completion of the 

center for activities to be taken through the end of fiscal year 2013. 

Page 36 GAO-10-68 Postmarket Drug Safety
 

programming work, although they described challenges associated with 

contracting out this type of work. The officials said that each drug safety 

study can take 1 to 2 years to complete and receiving programming 

support on a task-by-task basis requires OSE to spend time reeducating 

new programmers each time there is a new task. In contrast, an OSE 

official said that having programmers within CDER could allow them to 

gain expertise on the kind of work OSE does. 

FDA Has Encountered 

Difficulties Filling 

Vacancies for Its 

Increasingly Utilized 

Committee of External 

Drug Safety Experts 

FDA increasingly utilized external drug safety experts serving on DSaRM 

to participate in advisory committee meetings to discuss identified safety 

issues of specific products, but the agency faces challenges recruiting new 

members. From 2002 through 2006, DSaRM met 9 times in 5 years— 

5 times on its own as a committee and 4 times as part of joint meetings 

with other advisory committees. DSaRM met more frequently from 

January 2007 through December 2008, meeting 9 times—once on its own 

and 8 times as part of joint meetings. Most DSaRM meetings, and all 9 of 

the meetings in 2007 and 2008, have been held to discuss drug-specific 

issues. In addition to attending joint advisory committee meetings, 

individual DSaRM members served temporarily to supplement expertise 

during 12 meetings of other CDER advisory committees that occurred 

from 2007 through 2008.83 While several DSaRM members acknowledged 

the important expertise in drug safety that they can bring to discussions 

with other advisory committees, some members told us that the small 

number of meetings involving only DSaRM has resulted in a lack of 

cohesion among committee members. In addition, some members noted 

that meeting as a single committee would allow them to discuss broad 

principles of drug safety, rather than specific drug products, and to 

examine lessons learned across meetings. One member noted that without 

meeting as a single group on broad safety issues, the committee is unable 

to take advantage of the cumulative learning that comes with a coherent 

process. An FDA official said that the agency recognizes that temporarily 

serving on other advisory committees has been a burden for DSaRM 

members. The official said that, therefore, the agency has been expanding 

 

83In a January 2007 response to IOM’s drug safety report, FDA indicated that it would 

increase involvement of epidemiology expertise in advisory committee meetings, including 

by utilizing DSaRM members. 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, 

January 2007, http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrug

SafetyInformationforPatientsandProviders/UCM171627.pdf (accessed July 22, 2009). 

Page 37 GAO-10-68 Postmarket Drug Safety
 

a pool of consultants that can instead provide temporary drug safety 

expertise at these other advisory committee meetings.84

Despite the increased demand for DSaRM’s drug safety expertise, the 

agency has been challenged to fill all of the committee’s vacancies. For the 

past few years DSaRM has had between 6 and 9 of its 14 slots vacant. In 

contrast, from 2003 through 2006, DSaRM had no more than one vacancy.85

A few of the DSaRM members that we interviewed told us that additional 

members are needed to reduce the existing members’ workload. The OSE 

Director said that a more intensive effort to recruit members to the 

committee began in 2008, but it has been difficult to find qualified 

individuals who have no financial conflicts of interest.86 Recruiting new 

members will be especially important because 3 members’ terms expired 

on May 31, 2009. An official said that the agency appointed 3 new members 

to the committee on July 1, 2009. While this gives the committee a total of 

8 members, 3 of these members’ terms expire on May 31, 2010. An official 

said the agency is reviewing approximately 43 candidates for potential 

conflicts of interest, with the goal of filling the DSaRM vacancies as soon 

as possible. 

The number of vacancies may present challenges to FDA’s implementation 

of new FDAAA requirements for seeking advice from DSaRM on risk 

management plans and the analysis of drug safety data. FDA indicated that 

it plans to convene DSaRM in accordance with the FDAAA requirements, 

although officials said that the agency has not yet done so and the 

requirements will result in FDA using DSaRM differently than in the past. 

An official said that the agency is therefore in the process of determining 

how to best involve the committee in these new activities. Some of the 

 

84Consultant pools are lists of individuals who FDA has determined have expertise that may 

be needed in the future for a specific advisory committee meeting. FDA officials also told 

us that consultants may be former FDA advisory committee members. GAO, FDA Advisory 

Committees: Process for Recruiting Members and Evaluating Potential Conflicts of 

Interest, GAO-08-640 (Washington, D.C.: Sept. 30, 2008). 

85Although DSaRM was created in 2002 and held one meeting in that year, members were 

not appointed to the committee until 2003. The 2002 meeting was attended by nine 

temporary members, most of whom would be appointed as full members in 2003. 

86See 5 U.S.C. app. 2 § 5(b)(2). FDA advisory committees are subject to the Federal 

Advisory Committee Act, which requires that committee memberships also be fairly 

balanced in terms of views presented and the functions to be performed by the advisory 

committee. FDA is also experiencing similar recruitment difficulties for recruiting 

members of other committees as well. See GAO-08-640. 

Page 38 GAO-10-68 Postmarket Drug Safety
 

DSaRM members with whom we spoke noted that the FDAAA provisions 

appear to relate to broader drug safety issues than the committee has 

generally considered. One member noted that the committee would not be 

able to fulfill the new FDAAA requirements at product-specific meetings; 

rather, the complete committee would probably have to meet on its own. If 

the agency continues to have a large number of vacancies with DSaRM, it 

could be difficult for the committee to fulfill these additional duties while 

also participating in discussions of specific drug products. 

FDA’s oversight of postmarket drug safety has been a long-standing 

concern, with various groups reporting problems for more than 30 years. 

Our 2006 report on this topic cited the need for FDA to improve its 

decision-making process for postmarket drug safety. To enhance this 

process, FDA has recently begun to take steps that respond to our 

concerns, as well as those expressed by others. However, many of its 

initiatives are new and are in the early stages of development and 

implementation. For example, the agency’s efforts to begin formalizing its 

decision-making process, hire more staff, and establish dedicated safety 

positions within OND are an encouraging start. As FDA has gone about 

planning to improve its postmarket oversight, it has also needed to 

respond to changes brought about by FDAAA, which resulted in increased 

responsibilities for postmarket drug safety. FDA employees have since 

cited several instances in which increases in their workload and 

competing premarket demands and other priorities have prevented them 

from fully carrying out their postmarket drug safety responsibilities. We 

recognize that with a growing workload, come additional challenges. The 

agency’s initiatives will require time and resources before they can make a 

significant impact on previously identified problems. While we view FDA’s 

plans as positive, it is not yet clear if or when FDA’s decision-making 

process will be substantially improved as a result of its efforts. 

Conclusions 

As one of its efforts to enhance postmarket decision making, the agency 

plans to transfer additional authorities from OND to OSE. Transferring 

these authorities could help FDA better align decision-making 

responsibilities with the division of expertise between the two offices. 

However, the agency has set no time frames for their transfer and has 

stated that OSE needs increased experience and resources before the 

office is able to assume the new authorities. FDAAA provided the agency 

with greater flexibility to allocate funds to postmarket drug safety. 

Therefore, as FDA considers this transfer, it is important that it take 

advantage of this flexibility to align its resources in such a way that it 

strike an appropriate balance between its competing premarket and 

Page 39 GAO-10-68 Postmarket Drug Safety
 

postmarket priorities and ensure postmarket safety receives sufficient 

attention. Establishing a time frame for this transfer and adequately 

preparing OSE to assume these authorities are important next steps to 

ensuring appropriate oversight of postmarket drug safety. 

To address weaknesses in FDA’s oversight of postmarket drug safety, we 

recommend that the Commissioner of FDA develop a comprehensive plan 

for transferring the additional regulatory authorities from OND to OSE 

that includes time frames for the transfer and steps to ensure resources 

are properly aligned to allow OSE to assume these responsibilities. 

We provided a draft of this report to HHS for review. HHS provided 

comments from FDA, which agreed with our recommendation. FDA’s 

comments are reprinted in appendix II. FDA also provided technical 

comments, which we incorporated as appropriate. 

Recommendation 

Agency Comments 

and Our Evaluation 

Regarding our recommendation, FDA agreed that developing a 

comprehensive plan to prepare OSE for the transfer of additional 

regulatory authorities is desirable. However, it noted that the details of 

such a plan, including time lines, remain dependent upon available funding 

and the agency’s ability to recruit and retain the necessary staff to assume 

additional responsibilities. While we agree that both funding and staff are 

important to the successful transfer of these regulatory authorities, we 

believe that FDA has the flexibility to align its resources in such a way as 

to ensure that postmarket drug safety receives appropriate attention. 

Furthermore, we believe that the development of a comprehensive plan 

and time line is an important step towards ensuring that necessary funding 

levels and staffing needs are identified and secured. 

In addition to commenting on our recommendation, FDA addressed 

several other issues. First, it emphasized that, since our 2006 report was 

issued, it has undertaken a comprehensive set of activities to improve its 

postmarket drug safety program. We agree that FDA has begun to take 

some important steps to improve its decision-making process, but as we 

noted earlier, we believe that it is too early to judge the effectiveness of 

these steps. Second, FDA stressed that postmarket drug safety decisions 

are often complex and frequently require the involvement of staff from a 

number of scientific disciplines. The agency noted that for each of the 

many regulatory decisions that need to be made, a decision maker must 

have the delegated responsibility and authority to make these decisions. It 

indicated, for example, that in most cases OND has the broadest expertise 

Page 40 GAO-10-68 Postmarket Drug Safety
 

to make decisions about postmarket drug safety. We understand that, 

while multiple areas of expertise are brought to bear in assessing safety 

issues, there may need to be a single office responsible for making final 

decisions. We added language in the report to clarify FDA’s position on 

OND expertise in postmarket decision making. Third, it also noted that we 

implied that OND and OSE are the only significant participants in drug 

safety decision making. We understand that, depending on the safety issue, 

a variety of FDA offices and scientific disciplines may be involved in 

decision making and our draft report acknowledged this. However, our 

work appropriately focused on OND and OSE because of the key roles 

they play in postmarket decision making and because of the concerns that 

were raised about the relationship between these two offices in our 2006 

report. Finally, FDA said that our report omitted the contribution its Drug 

Safety Oversight Board has made to postmarket decision making. We 

recognize that this board plays a role in postmarket safety, as discussed in 

our 2006 report. The focus of our current report was to describe new 

initiatives underway at FDA. However, we have added information about 

the board to our report in response to FDA’s comments. 

As agreed with your office, unless you publicly announce the contents of 

this report earlier, we plan no further distribution until 30 days from the 

report date. At that time, we will send copies to the Commissioner of FDA 

and appropriate congressional committees. The report also will be 

available at no charge on the GAO Web site at http://www.gao.gov. If you 

or your staff have any questions about this report, please contact me at 

(202) 512-7114 or crossem@gao.gov. Contact points for our Offices of 

Congressional Relations and Public Affairs may be found on the last page 

of this report. GAO staff who made major contributions to this report are 

listed in appendix III. 

Sincerely yours, 

Director, Health Care 

Marcia Crosse 

Page 41 GAO-10-68 Postmarket Drug Safety
Appendix I: Status of FDA Actions Related to Appendix I: Status of FDA Actions Related to Our 2006 Recommendations 

Our 2006 Recommendations 

In our 2006 report,1 we made recommendations to the Food and Drug 

Administration (FDA) that were intended to improve its oversight of the 

postmarket drug safety decision-making process. Specifically, we 

recommended that FDA: 

1. revise and implement its draft policy on major postmarket drug safety 

decisions, 

2. clarify the Office of Surveillance and Epidemiology’s (OSE) role in 

FDA’s scientific advisory committee meetings involving postmarket 

drug safety issues, 

3. improve the Center for Drug Evaluation and Research’s (CDER) 

dispute resolution process by revising the pilot program for resolving 

differing professional opinions (DPO) to increase its independence,2

and 

4. establish a mechanism for systematically tracking OSE’s 

recommendations and subsequent safety actions. 

Regarding the draft policy on major postmarket drug safety decision 

making, according to FDA, the agency no longer plans to complete it. This 

policy was intended to ensure that all major postmarket safety 

recommendations be discussed by the relevant officials and present a 

process for making recommendations and resolving disagreements. An 

official said that, in light of the multidisciplinary approach it has 

established through the Safety First Initiative and principles of Equal 

Voice, FDA’s postmarket decision-making process has changed, and as a 

result, the process described in the draft policy was no longer relevant. 

The official said that the agency determined that it was not necessary to 

issue a separate policy on major postmarket drug safety decision making. 

Regarding the clarification of OSE’s role at scientific advisory committee 

meetings, an FDA official told us that instead of developing such a policy, 

 

1

GAO, Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and 

Oversight Process, GAO-06-402 (Washington, D.C.: Mar. 31, 2006). 

2

In our prior report, we referred to multiple FDA processes for resolving scientific disputes 

as “dispute resolution processes,” including what FDA terms as its DPO program. See 

GAO-06-402. For the purposes of this report, we use the term “dispute resolution” to refer 

to the broad category of processes involved in resolving scientific disputes, including the 

review of the dispute by the supervisory chain and DPO program. 

Page 42 GAO-10-68 Postmarket Drug Safety 
Appendix I: Status of FDA Actions Related to 

Our 2006 Recommendations 

the agency added language to the manual for the agency staff responsible 

for managing the advisory committees. The manual instructs these staff to 

ask the OND division coordinating an advisory committee meeting 

involving drug safety issues whether OSE should be involved in the 

meeting. This manual does not specifically address the role of 

presentations by OSE staff in those advisory committee meetings. 

However, an FDA official we spoke with was not aware of any recent 

instances in which OSE employees were excluded from presenting at an 

advisory committee meeting. Of the 30 OSE employees who completed our 

data collection instrument, 15 indicated that they had no opinion about the 

extent to which CDER has become more or less accepting of employees 

expressing dissenting views at advisory committee meetings. However, of 

the remaining 15 employees, 10 indicated that CDER has been more 

accepting of such presentations since 2006. 

Regarding CDER’s DPO program, FDA initiated an agencywide review of 

its dispute resolution process that instituted new requirements for each 

center to follow. CDER indicated that it is making few changes to its DPO 

policy, which an official told us already incorporated most of the new 

elements resulting from the agencywide review. However, according to a 

July 2009 draft of that policy, the planned changes do not address our 

recommendation to increase the program’s independence. A CDER official 

indicated that, under the revised policy, the Ombudsman would still 

consult with the CDER Director before deciding whether a dispute 

warrants formal review. In addition, the CDER Director is still the final 

decision maker regarding how the dispute should be resolved. 

Regarding the implementation of a mechanism for systematically tracking 

OSE’s recommendations and subsequent safety actions, FDA is in the 

process of implementing the Document Archiving, Reporting, and 

Regulatory Tracking System (DARRTS). In January 2007, in response to 

our 2006 recommendation, FDA began to incorporate a safety module 

within DARRTS to track the agency’s response to significant safety issues 

identified with the use of marketed drugs. For each significant safety 

issue, FDA creates a “tracked safety issue” within DARRTS that allows 

staff, among other things, to generate a workplan and assign 

responsibilities for managing these issues, as well as update their status. 

While the system contains documents describing specific 

recommendations and safety actions, an official told us that it does not, as 

we recommended, allow FDA to systematically track how issues were 

resolved and whether OSE’s recommendations were implemented. 

Page 43 GAO-10-68 Postmarket Drug Safety
Appendix II: Comments from the Department Appendix II: Comments from the Department of Health and Human Services 

of Health and Human Services 

Page 44 GAO-10-68 Postmarket Drug Safety 
Appendix II: Comments from the Department 

of Health and Human Services 

Page 45 GAO-10-68 Postmarket Drug Safety
Appendix II: Comments from the Department 

of Health and Human Services 

Page 46 GAO-10-68 Postmarket Drug Safety
Appendix II: Comments from the Department 

of Health and Human Services 

Page 47 GAO-10-68 Postmarket Drug Safety
Appendix III: GAO

A

 Contact and Staff 

cknowledgments 

Page 48 GAO-10-68 

Appendix III: GAO Contact and Staff 

Acknowledgments 

GAO Contact Marcia Crosse, (202) 512-7114, crossem@gao.gov. 

In addition to the contact named above, Geraldine Redican-Bigott, 

Assistant Director; William Hadley; Cathleen Hamann; Rebecca 

Hendrickson; Hannah Sypher Locke; Lisa Motley; Coy J. Nesbitt; and 

Suzanne Worth made key contributions to this report. 

 Postmarket Drug Safety 

Acknowledgments 

(290737) 
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