Flexibility over rigor: stakeholder acceptance of the limitations of confirmatory studies following accelerated approval

灵活性重于严谨性:利益相关者接受加速审批后验证性研究的局限性

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Abstract

INTRODUCTION: Concerns about completing postmarketing requirements (PMRs) following accelerated approval (AA) of new drugs have been well documented. However, there has been little examination of specific barriers and facilitators to timely, rigorous PMRs (eg, blinded, randomized trials in the approved population) from the perspective of key stakeholders. METHODS: To understand these factors, especially for cancer and rare diseases, we interviewed 56 regulators, industry executives, patient advocates, and payers. RESULTS: Stakeholders focused on predictable PMR barriers and, except for payers, offered weak solutions, including those that would trade rigor for feasibility (eg, avoiding randomization, conducting PMRs outside approved indications), could raise other concerns (eg, conducting PMRs abroad), or are likely to fall short (eg, patient education). Stakeholders supported requiring that confirmatory studies begin before AA but were unsure how to retain rigor thereafter, emphasized tradeoffs, and sought rare disease exceptions. Although regulators and payers supported payment reforms for AA drugs, all stakeholder groups questioned practicability. CONCLUSION: Stakeholders recognize PMR shortcomings but prioritize flexibility, raising questions about AA's foundations and suggesting that further documenting poor rigor is unlikely to change policy. Beyond recent reforms, future efforts should emphasize confirming benefit for rare disease AAs, encouraging PMR rigor, and exploring AA payment reform.

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