Comparison of FDA accelerated vs regular pathway approvals for lung cancer treatments between 2006 and 2018

Area of Science:

• Oncology
• Drug Regulation
• Clinical Trial Design

Background:

• Regulatory agencies worldwide, including the US Food and Drug Administration (FDA), increasingly utilize flexible approval pathways for new drugs, particularly in oncology.
• Accelerated pathways and breakthrough therapy designations (BTD) allow for faster drug approvals, often based on surrogate endpoints and preliminary data from smaller studies.
• The FDA's expedited review processes aim to bring novel cancer therapies to patients sooner, but raise questions about the robustness of supporting evidence.

Purpose of the Study:

• To compare FDA Accelerated vs. Regular Pathway approvals and Breakthrough Therapy Designations (BTD) for lung cancer treatments approved between 2006 and 2018.
• To analyze differences in study design, sample size, outcome measures (endpoints), and effect size between these FDA approval categories.
• To assess the quality of evidence supporting expedited lung cancer drug approvals.

Main Methods:

• A comprehensive assessment of the FDA drug approval database was conducted.
• Data were collected for new drug or indication approvals for lung cancer between 2006 and 2018.
• Key metrics analyzed included study design (e.g., single-arm vs. randomized), sample size, primary outcome measures (surrogate vs. clinical endpoints), and reported effect sizes.

Main Results:

• Accelerated pathway approvals frequently utilized single-arm studies with small sample sizes and surrogate primary endpoints.
• No significant difference in effect size was observed between accelerated and regular pathway approvals.
• Breakthrough Therapy Designations (BTD) were more often based on single-arm studies, with 44% demonstrating large effect sizes, proportionally more than other designations.
• A substantial proportion of studies supporting regular pathway approvals also exhibited characteristics associated with lower evidence quality.

Conclusions:

• The criteria for granting accelerated approval and breakthrough therapy designation appear unclear, based on the extracted evidence quality indicators.
• Expedited drug approvals for lung cancer are often characterized by uncertainties, necessitating cautious interpretation and transparent communication with patients for shared decision-making.
• Robust post-marketing validation of drugs approved through accelerated pathways and BTD is essential to confirm clinical benefit and ensure patient safety.