Regulation and Clinical Evidence

PORTAL researchers study how the FDA ensures medical products are safe and effective, and what additional evidence patients and doctors need to make informed clinical decisions.

Regulation & Clinical Evidence

Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

Liu ITT, Kesselheim AS, Cliff ERS | JAMA (2024)

Among a 5-year cohort of cancer drugs approved by the FDA under accelerated approval, only half of approvals demonstrated improvements in overall survival or quality of life in confirmatory trials, with 60% of conversions to full approval relying on clinical endpoints.

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Recent Work in Regulation & Clinical Evidence

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Use of Leucovorin After the FDA Announcement of Its Use for Autism Spectrum Disorders

Rome BN, Kim J, Figueroa JF, Kesselheim AS - Pediatrics

  • Regulation and Clinical Evidence
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Orphan Designation for Drugs Approved in the United States and European Union: A Comparative Analysis

Costa E, Ross JS, Kesselheim AS - Clinical Pharmacology & Therapeutics

  • Innovation Incentives and Competition
  • Regulation and Clinical Evidence
The US Orphan Drug Act and EU Orphan Regulation both offer incentives to develop rare disease treatments, but of 344 rare disease drug indications approved from 2011 to 2020, 97.7% received FDA Orphan Drug designation versus only 40.4% from the EMA, with the agencies aligning most on advanced therapies and genetic diseases but diverging on cancer subsets and pediatric indications of common diseases like HIV. These differences reflect the broader US indication-based framework versus the EU’s narrower focus on distinct conditions, suggesting policymakers should target incentives toward truly rare diseases rather than subsets of common conditions like cancer.
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What Utah’s Clinical AI Sandbox Reveals About Independent Oversight

Gorijavolu R, Jaiswal N, Kesselheim AS, Sakran JV, Hernandez-Boussard T, Celi LA - Nature Medicine

  • Regulation and Clinical Evidence
Utah became the first state to authorize an AI sandbox for prescription renewals, but a transparency audit of the pilot found that neither the participating company nor the state would release the underlying safety data, performance metrics, or adverse event reports, with operational metrics classified as protected trade secrets. Because a regulatory framework cannot rely on a company as the sole source of safety evidence, the authors propose a Registry of Independent AI Auditors that would mandate external evaluation as a condition of sandbox participation while preserving commercial confidentiality.
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