After a drug is on the market, FDA continues to assess its risks and  benefits. FDA Lacked a Clear and Effective Decision-making Process for Postmarket Drug Safety

In our March 2006 report, we found that FDA’s postmarket drug safety  decision-making process was limited by a lack of clarity, insufficient  oversight by management, and data constraints. We observed that there  was a lack of established criteria for determining what safety actions to  take and when, and aspects of ODS’s role in the process were unclear. Decision-making Process on Drug Safety Lacked Clarity about Criteria for Action and the Role of ODS

While acknowledging the complexity of the postmarket drug safety  decision-making process, we found through our interviews with OND and  ODS staff and in our case studies that the process lacked clarity about  how drug safety decisions were made and about the role of ODS. In those reviews FDA indicated that an absence of established criteria for  determining what safety actions to take, and when to take them, posed a  challenge for making postmarket drug safety decisions. The OND review division responsible  for Arava presented its own analysis of postmarket drug safety data at the  meeting, but did not allow the ODS staff—who had recommended that  Arava be removed from the market—to present their analysis because it  felt that ODS’s review did not have scientific merit. A Lack of Communication and Limited Oversight Hindered the Decision- making Process

A lack of communication between ODS and OND’s review divisions and  limited oversight of postmarket drug safety issues by ODS management  also hindered the decision-making process. Another problem was the lack of systematic information on  drug safety issues. Data Constraints Contributed to Difficulty in Making Postmarket Safety Decisions

Data constraints—such as weaknesses in data sources and FDA’s limited  ability to require certain studies and obtain additional data—contributed  to FDA’s difficulty in making postmarket drug safety decisions. We found that FDA’s access to postmarket clinical trial and observational  data was limited by its authority and available resources. FDA’s Initiatives to Improve Postmarket Drug Safety Decision Making

Prior to the completion of our March 2006 report, FDA began several  initiatives to improve its postmarket drug safety decision-making process. Most prominently, FDA commissioned the Institute of Medicine (IOM) to  convene a committee of experts to assess the current system for  evaluating postmarket drug safety, including FDA’s oversight of  postmarket safety and its processes. IOM issued its report in September  2006. For example, FDA established the Drug  Safety Oversight Board to help provide oversight and advice to the CDER  Director on the management of important safety issues. Since our report, FDA has made efforts to improve its postmarket safety  decision-making and oversight process. FDA has also begun several initiatives since our March 2006 report that we  believe could address three of our four recommendations. Because none  of these initiatives was fully implemented as of March 2007, it was too  early to evaluate their effectiveness. To make the postmarket safety decision-making process clearer and more  effective, we recommended that FDA revise and implement its draft policy  on major postmarket drug safety decisions. To make the postmarket safety decision-making process clearer, we  recommended that FDA clarify ODS’s role in FDA’s scientific advisory  committee meetings involving postmarket drug safety issues. The policy is also expected to clarify ODS’s role in planning for,  and participating in, meetings of FDA’s scientific advisory committees. We also suggested in our report that Congress consider expanding FDA’s  authority to require drug sponsors to conduct postmarket studies in order  to ensure that the agency has the necessary information, such as clinical  trial and observational data, to make postmarket decisions.
Why GAO Did This Study

GAO was asked to testify on the effectiveness of the Food and Drug Administration's (FDA) postmarket decision-making process. This testimony is based on Drug Safety: Improvement Needed in FDA's Postmarket Decision-making and Oversight Process, GAO-06-402 (March 31, 2006). The report focused on the complex interaction between two offices within FDA that are involved in postmarket drug safety activities: the Office of New Drugs (OND), and the Office of Drug Safety (ODS). OND's primary responsibility is to review new drug applications, but it is also involved in monitoring the safety of marketed drugs. ODS is focused primarily on postmarket drug safety issues. ODS is now called the Office of Surveillance and Epidemiology. For its report, GAO reviewed FDA policies, interviewed FDA staff, and conducted case studies of four drugs with safety issues: Arava, Baycol, Bextra, and Propulsid. To gather information on FDA's initiatives since March 2006 to improve its decision-making process for this testimony, GAO interviewed FDA officials and reviewed FDA documents in February and March 2007.

What GAO Found

In its March 2006 report, GAO found that FDA lacked clear and effective processes for making decisions about, and providing management oversight of, postmarket drug safety issues. There was a lack of clarity about how decisions were made and about organizational roles, insufficient oversight by management, and data constraints. GAO observed that there was a lack of criteria for determining what safety actions to take and when to take them. Certain parts of ODS's role in the process were unclear, including ODS's participation in the meetings of scientific advisory committees organized by OND to discuss safety issues for specific drugs. In the case of Arava, for example, ODS staff were not allowed to present their analysis of postmarket safety at an advisory committee meeting held to review Arava's safety risks and benefits. Insufficient communication between ODS and OND hindered the decision-making process. ODS management did not systematically track information about ongoing postmarket safety issues, including the recommendations that ODS staff made for safety actions. GAO also found that FDA faced data constraints that contributed to the difficulty in making postmarket safety decisions. GAO found that there were weaknesses in the different types of data available to FDA, and FDA's access to data was constrained by both its authority to require certain studies and its limited resources. During the course of GAO's work for its March 2006 report, FDA began a variety of initiatives to improve its postmarket drug safety decision-making process, including the establishment of the Drug Safety Oversight Board. FDA also commissioned the Institute of Medicine to examine the drug safety system, including FDA's oversight of postmarket drug safety. GAO recommended in its March 2006 report that FDA take four steps to improve its decision-making process for postmarket safety. GAO recommended that FDA revise and implement its draft policy on the decision-making process for major postmarket safety actions, improve its process to resolve disagreements over safety decisions, clarify ODS's role in scientific advisory committees, and systematically track postmarket drug safety issues. FDA has initiatives underway and under consideration that, if implemented, could address three of GAO's four recommendations. Because none of these initiatives was fully implemented as of March 2007, it was too early to evaluate their effectiveness. In the 2006 report GAO also suggested that Congress consider expanding FDA's authority to require drug sponsors to conduct postmarket studies, as needed, to collect additional data on drug safety concerns.