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Approval of cancer drugs with uncertain therapeutic value: a comparison of regulatory decisions in Europe and the United States

Salcher-Konrad, Maximilian ORCID: 0000-0002-5628-5266 and Salcher-Konrad, Maximilian ORCID: 0000-0002-5628-5266 (2020) Approval of cancer drugs with uncertain therapeutic value: a comparison of regulatory decisions in Europe and the United States. Milbank Quarterly. ISSN 0887-378X (In Press)

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Context: Regulatory agencies are increasingly required to make market approval decisions for new drugs on the basis of limited clinical evidence, a situation commonly encountered in cancer. We aimed to investigate how regulators manage uncertainty in the benefit-risk profiles of new cancer drugs by comparing decisions for the world’s two largest regulatory bodies (United States Food and Drug Administration, FDA, and European Medicines Agency, EMA) over a 5-year period. Methods: We systematically identified a set of cancer drug-indication pairs for which data on efficacy and safety was less complete than that required for regular approval at time of market entry from 2009-2013, as determined by FDA’s use of Accelerated Approval (AA) or EMA’s use of Conditional Marketing Authorization (CMA) pathways, and matched these across the two agencies. Using publicly available information, we compared regulatory pathways and outcomes, final approved indications, and post-marketing obligations imposed by the agencies. Findings: We identified 21 cancer drug-indication pairs that received FDA AA, EMA CMA, or both. While most applications relied on identical pivotal trials across FDA and EMA, regulatory pathways often differed (57% of indications received either FDA AA or EMA CMA, and regular approval by the other agency). After approval, EMA more often accepted single-arm studies to confirm clinical benefit compared to FDA (75% vs. 29% of indications), and FDA more commonly requested randomized controlled trials (85% vs. 50%). 41% of confirmatory trials after FDA AA were conducted in different populations than the approved indication, compared to 13% after EMA CMA. Both agencies relied primarily on surrogate measures of patient benefit for post-marketing obligations. After a median follow-up of 7.25 years, 40% of FDA and 61% of EMA post-marketing obligations after AA and CMA, respectively, were delayed. Conclusions: US and European regulators often deemed early and less complete evidence on benefit-risk profiles of cancer drugs sufficient to grant regular approval, raising questions over regulatory standards for the approval of new medicines. Even when imposing confirmatory studies in the post-marketing period through special approval pathways, meaningful evidence may not materialize due to shortcomings in study design and delays in conducting required studies with due diligence.

Item Type: Article
Official URL:
Additional Information: © 2020 Milbank Memorial Fund
Divisions: Personal Social Services Research Unit
LSE Health
Subjects: R Medicine > RS Pharmacy and materia medica
Date Deposited: 13 May 2020 11:33
Last Modified: 20 Jul 2020 14:27

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