August 13, 2018
The FDA says sponsors considering adaptive studies for early phase cancer treatments should focus on patients with no other options. The agency notes that so-called expansion cohort trials — which start out relatively small but expand if a potential treatment shows promise — can be a way to get a treatment to market more quickly. The thinking is, the more participants in earlier trials the more likely it is to find and fix (if possible) glitches — ensuring faster approval or scrapping the potential treatment in its infancy if it doesn’t work or if risks outweigh benefits. “A lot of time and cost of clinical development is spent waiting in between the start and end of the phases of trials,” FDA Commissioner Scott Gottlieb said in a statement. “Expansion cohort trials can bring efficiency to drug development, potentially reducing development costs and time.” In a 17-page draft guidance released last week, the FDA says it wants to “establish an infrastructure” designed to help sponsors use cohorts to speed drug approvals without compromising safety. Its top recommendation: Focus on patients who are most seriously ill and don’t have any other treatment options. The agency also encourages researchers to hire centralized data management committees and IRBs and have them meet regularly to discuss latest findings and best next steps. “It is critical that investigators, IRBs and regulators are updated with new safety information so that they can provide the necessary oversight for the protection of human subjects and so that investigators can ensure that patients can provide adequate informed consent,” the draft document says. The jury’s still out on the effect of expansion cohorts. A 2017 study by Texas researchers, published in the Journal of the American Association for Cancer Research, analyzed 533 Phase I cancer trials between 2006 and 2011. They found the ones that used expansion cohorts went on to have successful Phase II trials at nearly twice the rate (48 percent) as studies that didn’t (27 percent). But just a year earlier, a team of Cleveland researchers analyzed 252 cancer trials conducted between 2004 and 2014 and found expansion cohorts made little or no statistical difference between success or failure in Phase II trials. Read the FDA’s draft guidance here: www.fdanews.com/08-10-18-DraftGuidance.pdf.