SC Connecticut News

Researchers at Yale's Collaboration for Regulatory Rigor, Integrity, and Transparency (CRRIT) have conducted two studies examining the U.S. Food and Drug Administration (FDA) approval process for cancer drugs and its impact on patients and clinicians. The studies were led by Maryam Mooghali, MD, MSc, a postdoctoral associate at CRRIT, and Reshma Ramachandran, MD, MPP, MHS, an assistant professor of general internal medicine and co-director of CRRIT.

The FDA offers four expedited review pathways for drug approval to accelerate access to treatments for serious or life-threatening diseases. One such pathway is accelerated approval based on surrogate markers or proxy measures that are "reasonably likely" to predict patient outcomes. Post-approval trials are required to confirm the clinical benefits of these drugs.

The first study published in BMJ Medicine found that National Comprehensive Cancer Network (NCCN) guidelines sometimes continue recommending accelerated approval drugs even when post-approval studies fail to confirm their clinical benefit or when they are withdrawn by the FDA. Additionally, NCCN guidelines often do not indicate that these drugs were approved based on surrogate markers rather than clinical outcomes or provide information on ongoing confirmatory trials.

The authors concluded that NCCN guidelines should be updated promptly in alignment with FDA regulatory decisions. They recommend including explicit rationales when there is a lack of agreement between NCCN guidelines and FDA decisions or trial results.

The second study examined cancer medications approved through the Real-Time Oncology Review (RTOR) program from 2018 to 2023. Published in JAMA Network Open, this cross-sectional study found that one-fifth of new FDA oncology indication approvals were reviewed under RTOR since its inception in 2018. Most approvals were based on surrogate markers without required post-approval studies to confirm clinical benefits.

Mooghali expressed concern over the implications for patient care: “It was surprising that the FDA has approved a significant proportion of cancer drugs through this even faster approval pathway based on surrogate markers and without any requirements to confirm that they improve survival or quality of life for patients.”

Ramachandran emphasized the need for changes in the FDA approval process: “Our studies point to the need for FDA to take action to relieve the burden of uncertainty around new drugs for patients and their doctors."

Yale CRRIT recently received a multi-million dollar three-year renewal grant from Arnold Ventures to support continued research into medical product evaluation, approval, and coverage aimed at improving patient outcomes. Arnold Ventures focuses on evidence-based solutions to pressing national issues.

In addition to conducting research, Yale CRRIT disseminates findings and recommendations to key stakeholders including legislators, federal agencies, patient advocacy organizations, among others.