The trade‑off between faster access and evidentiary certainty in the FDA’s Accelerated Approval of cancer drugs: empirical evidence on patient preferences and regulatory decision‑making

Background: When approving new drugs, the US Food and Drug Administration (FDA) must balance a trade-off between providing earlier access to new drugs and accepting greater uncertainty about a drug’s clinical benefit. In 1992, the FDA introduced the Accelerated Approval pathway to expedite access to new drugs. While the use of Accelerated Approval has shortened clinical development and approval times as intended, it has also led to greater uncertainty about the clinical benefit of new drugs at approval. Evidence shows that most cancer drugs receiving Accelerated Approval do not help patients with cancer live longer or improve their quality of life – outcomes that matter most to patients. Aims: This thesis aimed to better understand the extent to which individuals are willing to accept greater uncertainty in exchange for faster access to new cancer drugs, and whether factors beyond clinical data supporting approval may influence the FDA’s oversight of cancer drugs receiving Accelerated Approval. Methods: Mixed-methods. Key findings: The first two studies in this thesis find that individuals with experience of cancer may be willing to wait longer for FDA approval in exchange for greater certainty of a drug’s clinical benefit, and that patients are most likely to accept greater uncertainty only when no treatment alternatives exist or when the anticipated benefits are likely to be transformative. The third study finds that empirical evidence in support of claims that clinical or non-clinical factors influence FDA approval decisions is limited. The final study finds that many FDA conversion–withdrawal decisions diverge from mandated post-marketing study outcomes, suggesting the application of case-specific discretion and nuance, while not ruling out the influence of other factors beyond clinical evidence. Conclusion: Findings from this thesis demonstrate that FDA decisions made under conditions of uncertainty may not always reflect patients’ preferences and underscore the complexity of FDA cancer drug approval and post-market oversight.