FDA: New Guidance for Expansion Cohort Trials

August 20, 2018

Expansion cohorts can help bring life-saving drugs to market quickly, but sponsors should be sure to update informed consent for patients and convene expert safety panels that meet regularly, the FDA says in new draft guidance.

In the 17-page draft, the agency says it wants to “establish an infrastructure” to help sponsors use cohorts to expand oncology trials swiftly without compromising safety. But that means sponsors would have to stay on top of rapidly changing developments—and keep their patients in the loop, too.

“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 document stresses.

On its face, the recommendations aren’t radical, but they do acknowledge the pace at which these kind of adaptive trials are being adopted, says Lindsay McNair, chief medical officer at WCG Clinical.

“I think [the FDA] recognizes that these studies are unique in both the type of safety data that is accumulating during them and the speed and volume at which the data may be accumulated,” she says.

Perhaps the most well-known drug to come through an expansion cohort trial is Merck’s anti-cancer blockbuster Keytruda, which some analysts predict could reach $10 billion in annual sales. The drug, which hit the market in May 2017, has been approved for treatment of 10 different types of cancer.

Dozens of other, similar drugs are in the pipeline, FDA records show. lists nearly 147 expansion cohort trials completed in recent years—and another 416 in some stage of development.

Despite the successes, not everyone is on board. Some researchers worry expansion trials open the door to potential safety gaps — an issue the FDA hopes oversite committees can keep an eye on and avoid. Plus, the jury’s still out on whether adding cohorts enhances the success rate in later trials by catching and fixing possible snags early.

A 2017 study, published in a Journal of the American Association for Cancer Research, analyzed 533 phase I cancer trials between 2006 and 2011. It found the ones that used expansion cohorts went on to have successful phase II trials at nearly twice the rate (48 percent) as those that didn’t (27 percent). But just a year earlier, a team of 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.

Still, WCG’s McNair says there’s no question they help researchers “get to decision-making points more quickly.” And the FDA believes that with recommended new protections, they’ll prove to be a safe, quick way to bring new potentially vital meds to people who need them.

“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.”

Read the FDA’s draft guidance here:


-By Bill Myers