WASHINGTON, DC—The FDA is in need of a conceptual framework to help the agency evaluate the ethical issues involved in determining whether companies should start or continue clinical trials on approved drugs and in ensuring that these studies are ethically conducted, according to an IoM report released last month.

The agency recently gained authority to require drug companies to undertake studies of their products after they are put on the market, which presents the agency with additional challenges. The IoM report’s proposed framework underscores the importance of FDA’s decision-making processes and study design considerations.

The IoM committee highlighted the need to make sure post-marketing studies are warranted before calling into question an approved drug’s efficacy and safety. FDAshould ensure that any trial to evaluate the efficacy and safety of an approved drug suspected of causing serious adverse events is conducted only when the existing evidence and any evidence from new observational studies would be insufficient to enable the agency to make responsible policy decisions. The agency should also determine that questions about a drug’s possible risks or risk-benefit balance rise to the level of requiring a policy decision, such as whether to revise the product’s label.

In addition, the report states FDA should make sure that trials are appropriately designed to resolve uncertainties about efficacy and safety and to minimize risks to participants. Risks should be judged acceptable by appropriate oversight bodies, and participants and studies should be continuously monitored to assure that the risks continue to be acceptable. The process of informed consent should continue over the course of the trials, and participants should be promptly advised of substantial changes in clinical practice or professional standards and new research findings that could affect their willingness to accept the risks associated with a trial.

The report responds to one of several questions FDA asked IoM to explore in a review of ethical and scientific issues related to studying the safety of drugs on the market. Specifically, it addresses the ethical and informed consent issues that must be considered when designing randomized clinical trials to evaluate potential safety risks.

The report remains incomplete, with only an early draft being released last month. FDA requested an initial report on the ethical issues in advance of a meeting scheduled for July to discuss the case of the diabetes drug Avandia®. The report addresses the issues at play in this case, but does not delve into or respond to the specifics of the Avandia case. A more detailed analysis is scheduled for release with the IoM committee’s final report due in spring 2011.

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