Drug Safety:

Improvement Needed in FDA's Postmarket Decision-making and Oversight Process

GAO-06-402: Published: Mar 31, 2006. Publicly Released: Apr 24, 2006.

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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.

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.

Status Legend:

More Info
  • Review Pending-GAO has not yet assessed implementation status.
  • Open-Actions to satisfy the intent of the recommendation have not been taken or are being planned, or actions that partially satisfy the intent of the recommendation have been taken.
  • Closed-implemented-Actions that satisfy the intent of the recommendation have been taken.
  • Closed-not implemented-While the intent of the recommendation has not been satisfied, time or circumstances have rendered the recommendation invalid.
    • Review Pending
    • Open
    • Closed - implemented
    • Closed - not implemented

    Matter for Congressional Consideration

    Matter: To improve the decision-making process for postmarket drug safety, the Congress may wish to consider expanding FDA's authority to require drug sponsors to conduct postmarket studies, such as clinical trials or observational studies, as needed, to collect additional data on drug safety concerns.

    Status: Closed - Implemented

    Comments: In 2006, we reported that several high-profile drug safety cases in 2004 had raised concerns about the Food and Drug Administration's (FDA) management of safety issues concerning drugs that have been approved for marketing. Among other findings, we found that FDA faces data constraints in making postmarket safety decisions. We found that there are weaknesses in the different types of data available to FDA and FDA lacks authority to require certain studies for obtaining data. Consistent with the matter for Congressional consideration that we put forth, Congress expanded FDA's authority through the Food and Drug Administration Amendments Act of 2007, which the President signed into law on September 27, 2007. Among other provisions, this law gives FDA authority to require drug sponsors to conduct postmarket studies to collect additional data on drug safety concerns.

    Recommendations for Executive Action

    Recommendation: To improve the postmarket drug safety decision-making process, the Commissioner of FDA should improve the Center for Drug Evaluation and Research's dispute resolution process by revising the pilot program to increase its independence.

    Agency Affected: Department of Health and Human Services: Public Health Service: Food and Drug Administration

    Status: Open

    Comments: In September 2007, FDA indicated that a Manual of Policies and Procedures entitled "Documenting Differing Professional Opinions and Dispute Resolution - Pilot Program" is in draft form. It includes a pilot procedure for CDER staff to express differing professional opinions concerning regulatory actions or policy decisions with significant public health impacts in instances when the normal procedures for resolving disputes are not sufficient. This draft manual is currently under internal review.In 2009, an agency official stated the Center for Drug Evaluation and Research is in the process of revising the Differing Professional Opinions policy, but they have not set a date yet for completing the revision. CDER is making a few changes to its policy, but CDER stated the planned changes do not address GAO's recommendation to increase the program's independence.

    Recommendation: To improve the postmarket drug safety decision-making process, the Commissioner of FDA should, with input from the Drug Safety Oversight Board and the Process Improvement Teams, revise and implement the draft policy on major postmarket drug safety decisions.

    Agency Affected: Department of Health and Human Services: Public Health Service: Food and Drug Administration

    Status: Closed - Not Implemented

    Comments: In September 2007, FDA indicated that the Center for Drug Evaluation and Research has developed a Manual of Policies and Procedures entitled, "Documenting Professional Opinions and Dispute Resolution - Pilot Program." This document is in draft form and is currently under internal review.In 2009, FDA stated they no longer plan to implement a draft policy on post-market drug safety decision-making. An FDA official stated that the post-market drug safety decision-making process has changed and as a result, the process described in its draft policy is no longer relevant. As a result, the agency does not feel it is necessary to issue a separate post-market drug safety decision-making policy.

    Recommendation: To improve the postmarket drug safety decision-making process, the Commissioner of FDA should establish a mechanism for systematically tracking ODS's recommendations and subsequent safety actions.

    Agency Affected: Department of Health and Human Services: Public Health Service: Food and Drug Administration

    Status: Closed - Implemented

    Comments: In September 2007, FDA indicated that a new tracking system to systematically track post-market drug safety issues is being developed as a part of the Document Archiving, Reporting, and Regulatory Tracking System. Training of employees on this post-market drug safety system is currently underway. In January 2007, FDA began incorporating a safety module within the Document Archiving, Reporting, and Regulatory Tracking System (DARRTS) to track the agency's response to significant safety issues identified with the use of marketed drugs. For every significant safety issue, the agency creates a (tracked safety issue (TSI) in DARRTS. In June 2009, the agency published a manual of policies and procedures for tracking significant postmarket safety issues related to drugs in the DARRTS system.

    Recommendation: To improve the postmarket drug safety decision-making process, the Commissioner of FDA should clarify ODS?s role in FDA's scientific advisory committee meetings involving postmarket drug safety issues.

    Agency Affected: Department of Health and Human Services: Public Health Service: Food and Drug Administration

    Status: Open

    Comments: In September 2007, FDA reported that the Center for Drug Evaluation and Research has implemented a restructuring to facilitate improvements in regulatory and drug development science and how to evaluate and ensure the safety and efficacy of the products FDA regulates. However, FDA response did not include a clarification of ODS's role in FDA's scientific advisory committee meetings involving postmarket drug safety issues. In 2009, FDA stated that instead of developing a policy clarifying ODS's role in meetings, they added language to the manual for agency staff responsible for managing the scientific advisory committees. The manual instructs staff to ask the OND division coordinating an advisory committee meeting on postmarket drug safety issues whether OSE should be involved in the meetings, but doesn't address OSE's role in giving presentations during the meetings.

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