Approval Should Not Be the “Last Call” for Realistic Regulatory Action on Safety

In acknowledgement of the complexity of regulatory decision-making, the multiple conflicting interests involved, and the undesirability of delaying the approval of important drugs, the committee has sought to recommend tools that will allow FDA greater regulatory flexibility postapproval and throughout a drug’s lifecycle. Establishing an interval for reviewing all accumulated information about new molecular entities (NMEs) will provide FDA with the authority to take necessary regulatory action when appropriate. For most drugs, the review of the drug’s performance for renewal of approval will be a relatively simple process. For others, the review of postapproval data will give FDA an opportunity to reconsider the drug’s risk-benefit profile and respond to safety issues.

Over the years, patient groups and industry representatives have expressed concern that regulatory actions that are too risk-averse could stifle innovation in drug development. Longer and larger preapproval trials to improve certainty about a drug’s risk and benefit at the time of approval are often not possible, because the extremely broad-based testing in complex populations needed to get a better picture of postapproval use and risks would slow drug development unacceptably in many disease settings. Many scientists agree that CDER needs better resources for research and surveillance and better regulatory tools to manage risk-benefit uncertainty after approval (Deyo, 2004; Avorn, 2006; Ray and Stein, 2006). In earlier chapters, the committee described an organizational culture and a scientific milieu that encourage thinking about and preparing to address postmarketing safety issues much earlier in the development and review process. In this chapter, the committee calls for strengthening FDA’s authority so that the point of approval would no longer be the “last call” for major regulatory action.

The committee finds that FDA’s authority is built on an aging regulatory framework, that FDA’s largely all-or-nothing regulatory tools limit its ability to regulate effectively after approval, and that strengthened agency authority would greatly mitigate the concern that fast review and approval may sacrifice safety. Current enforcement options limit FDA’s ability to regulate in a manner that matches the agency’s mission—protecting and advancing the health of the public. FDA’s strongest tools are largely all-or-nothing, and these are unrealistic options in light of patients’ needs for given drugs. The agency needs a more nuanced set of tools to respond to uncertainty, to reduce advertising that drives rapid uptake of new drugs, or to compel additional studies in the actual patient populations who take the drug after its approval.

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