FDA Promotes Surrogate Endpoints, “Seamless” Clinical Trials

As part of efforts to speed patient access to effective new therapies, FDA is rolling out policies designed to streamline drug development, particularly for new cancer therapies to treat life-threatening conditions. A new guidance outlines how sponsors may compress the traditional three-phase trial into one continuous, or “multiple expansion cohort study,” to reduce the time and cost involved in devising trials for early stages of multi-phase oncology research programs.

The draft guidance maps out the process for shifting from the traditional clinical trial process to a continuous, or adaptive, study to expedite the conduct of first-in-human studies for patient populations with serious diseases where no cure is available [see https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM616325.pdf]. This approach utilizes a single protocol with an initial dose-escalation phase to determine a potentially effective dose. That dose then can be evaluated for safety and effectiveness in additional patient cohorts, similar to the role of phase 2 studies. FDA recognizes that such trails may expose patients to drugs with unknown toxicity and possibly limited benefit, and thus limits this approach to studies involving individuals with serious conditions. The agency also requires sponsors to establish systems for rapid data collection and evaluation and for continual oversight to quickly detect unexpected results.

FDA also is encouraging wider use of surrogate endpoints in clinical research by publishing a list of those markers that sponsors have used to gain approval of new drugs and biologics. The list was specified by the 21st Century Cures Act to facilitate medical product development. It provides information on surrogate endpoints that have supported market applications, as well as those utilized as primary endpoints in trials, but not as the basis for filing an NDA or BLA [see https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm613636.htm]. FDA notes that it will evaluate the use of surrogate endpoints in a particular development program on a case-by-case basis, and that it will update the list every six months.

FDA commissioner Scott Gottlieb heralded the seamless trial approach as a way to avoid costly and long delays between the end and start of clinical study phases [see https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM616325.pdf]. FDA outlines in the guidance which drugs are best suited for expansion cohort studies, what information sponsors should provide in INDs to support such studies, safeguards needed to protect patients, and when to consult FDA on planning and conducting these types of innovative studies. A main theme promoted by commissioner Gottlieb is that more efficient research approaches can lower the cost of drug development and translate into less expensive new therapies, but such benefits have not been that apparent.

Jill Wechsler is the Washington Correspondent for Applied Clinical Trials.