ODS has a  primary focus on postmarket drug safety and provides consultation to  OND. ODS has been reorganized several times over the years, and there  has been an absence of stable leadership. OND Has Decision-making Responsibility for Postmarket Drug Safety

Since OND is responsible for approving or disapproving drug applications,  its staff are involved in safety activities throughout the life cycle of a drug  (that is, premarket and postmarket), and it has the ultimate responsibility  to take regulatory action concerning the postmarket safety of drugs. OND  receives information about safety issues in several ways. There has been high turnover of ODS directors—there have been eight  different directors of the office and its various predecessors—in the past  10 years. FDA Lacks a Clear and Effective Decision-making Process for Postmarket Drug Safety

FDA’s postmarket drug safety decision-making process has been limited  by a lack of clarity, insufficient oversight by management, and data  constraints. We observed that there is a lack of established criteria for  determining what safety actions to take and when. Aspects of ODS’s role  in the process are unclear, including its role in participating in scientific  advisory committee meetings organized by OND. A lack of communication  between ODS and OND’s review divisions and limited oversight of  postmarket drug safety issues by ODS management has hindered the  decision-making process. Decision-making Process on Drug Safety Lacks Clarity about Criteria for Action and the Role of ODS

While acknowledging the complexity of the postmarket drug safety  decision-making process, we observed in our interviews with OND and  ODS staff and in our case studies that the process lacked clarity about  how drug safety decisions are made and about the role of ODS. Data Constraints Contribute to Difficulty in Making Postmarket Safety Decisions

Data constraints—such as weaknesses in data sources and limitations in  requiring certain studies and obtaining data—contribute to FDA’s  difficulty in making postmarket drug safety decisions. FDA Initiatives Are an Improvement, but Will Not Address All Gaps

FDA has undertaken several initiatives to improve the postmarket drug  safety decision-making process, but these are unlikely to address all the  gaps. FDA’s newly created Drug Safety Oversight Board (DSB) may help  provide oversight of important, high-level safety decisions, but it does not  address the need for systematic tracking of ongoing safety issues. Other  initiatives, such as FDA’s draft policy on major postmarket drug safety  decisions and communication initiatives may help improve the clarity and  effectiveness of the process, but they have not been fully implemented. FDA Is Taking Steps to Identify Additional Data Sources, but Constraints Remain

FDA is taking steps to identify additional data sources that it may obtain  with its current authority and resources. Recommendations for Executive Action

To improve the postmarket drug safety decision-making process, we  recommend that the Commissioner of FDA take the following four actions:    establish a mechanism for systematically tracking ODS’s  recommendations and subsequent safety actions;    with input from the DSB and the Process Improvement Teams, revise and  implement the draft policy on major postmarket drug safety decisions;  improve CDER’s dispute resolution process by revising the pilot program  to increase its independence; and    clarify ODS’s role in FDA’s scientific advisory committee meetings  involving postmarket drug safety issues. Nonetheless, ODS does not  have any independent decision-making responsibility while OND has the  ultimate responsibility to make decisions about regulatory actions  concerning the postmarket safety of drugs. In this case there was general agreement about the safety concern  between the Office of New Drugs (OND) and the Office of Drug Safety  (ODS), but differing opinions within the Food and Drug Administration  (FDA) over what safety actions should be taken regarding the drug.
Why GAO Did This Study

In 2004, several high-profile drug safety cases raised concerns about the Food and Drug Administration's (FDA) ability to manage postmarket drug safety issues. In some cases there have been disagreements within FDA about how to address safety issues. In this report GAO (1) describes FDA's organizational structure and process for postmarket drug safety decision making, (2) assesses the effectiveness of FDA's postmarket drug safety decision-making process, and (3) assesses the steps FDA is taking to improve postmarket drug safety decision making. GAO conducted an organizational review and case studies of four drugs with safety issues: Arava, Baycol, Bextra, and Propulsid.

What GAO Found

Two organizationally distinct FDA offices, the Office of New Drugs (OND) and the Office of Drug Safety (ODS), are involved in postmarket drug safety activities. OND, which holds responsibility for approving drugs, is involved in safety activities throughout the life cycle of a drug, and it has the decision-making responsibility to take regulatory actions concerning the postmarket safety of drugs. OND works closely with ODS to help it make postmarket decisions. ODS, with a primary focus on postmarket safety, serves primarily as a consultant to OND and does not have independent decision-making responsibility. ODS has been reorganized several times over the years. There has been high turnover of ODS directors in the past 10 years, with eight different directors of the office and its predecessors. In the four drug case studies GAO examined, GAO observed that the postmarket safety decision-making process was complex and iterative. FDA lacks clear and effective processes for making decisions about, and providing management oversight of, postmarket safety issues. The process has been limited by a lack of clarity about how decisions are made and about organizational roles, insufficient oversight by management, and data constraints. GAO observed that there is 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 are unclear, including ODS's participation in FDA's scientific advisory committee meetings organized by OND. Insufficient communication between ODS and OND has been an ongoing concern and has hindered the decision-making process. ODS does not track information about ongoing postmarket safety issues, including the recommendations that ODS staff make for safety actions. FDA faces data constraints in making postmarket safety decisions. There are weaknesses in the different types of data available to FDA, and FDA lacks authority to require certain studies and has resource limitations for obtaining data. Some of FDA's initiatives, such as the establishment of a Drug Safety Oversight Board, a draft policy on major postmarket decision making, and the identification of new data sources, may improve the postmarket safety decision-making process, but will not address all gaps. FDA's newly created Drug Safety Oversight Board may help provide oversight of important, high-level safety decisions, but it does not address the lack of systematic tracking of ongoing safety issues. Other initiatives, such as FDA's draft policy on major postmarket decisions and regular meetings between OND divisions and ODS, may help improve the clarity and effectiveness of the process, but they are not fully implemented. FDA has not clarified ODS's role in certain scientific advisory committee meetings. FDA's dispute resolution processes for disagreements about postmarket safety decisions have not been used. FDA is taking steps to identify additional data sources, but data constraints remain.