Use of Master Protocols Expected to Grow in Wake of FDA Guidance
The use of master protocols in the U.S. will likely increase and expand into more treatment areas now that the FDA has signaled support for the practice in a new final guidance for COVID-19 trials last week.
Pamela Tenaerts, former executive director of the Clinical Trials Transformation Initiative (CTTI) and current chief scientific officer at Medable, said she was not surprised that the guidance emerged from an FDA with Acting FDA Commissioner Janet Woodcock at the helm.
“She is very keen, and I think the FDA is in general, to make clinical trials more efficient,” Tenaerts told CenterWatch Weekly. “That’s not to say that this is a panacea for how every research trial should be done, but there are situations — especially when you’re talking about things like repurposed drugs — where it makes good sense to have a clinical trial with one control arm and then multiple treatment arms.”
Lindsay McNair, chief medical officer at WCG, echoed Tenaerts’ sentiments. “While the startup timelines of new clinical trials for COVID-19 therapies have been remarkable, the FDA guidance rightly points out that master protocols are a rigorous and highly efficient way to answer multiple important study questions while reducing infrastructure effort and administrative time and effort,” McNair says. “We’ve certainly seen this in the example of the UK-run RECOVERY clinical trial master protocol, which has randomized almost 40,000 participants, tested multiple potential therapies and generated important and well-controlled data on several interventions for COVID-19 treatment.
“This guidance gives a lot more muscle to master protocols,” Tenaerts adds, “which is very encouraging. That’s not to say we weren’t using master protocols. We were. We just weren’t quite as organized as the UK.”
While the guidance is directed at single sponsors, McNair points out that there are few sponsors who have multiple products in development for COVID-19 solutions. According to data from WCG’s Knowledge Base, 73 percent of sponsors involved in COVID-19 research are conducting only one trial, 22 percent are conducting two to four trials and only 5 percent are conducting five or more studies.
“Collaboration between sponsors to use the same master protocol is certainly possible,” she adds, “and hopefully some of the collaborations and partnerships we have seen developing in the past year could contribute to this.”
In its May 17 guidance, the FDA said master protocols, when designed and executed effectively, can accelerate drug development by evaluating multiple drugs at the same time and maximizing the amount of information gained during research compared to standalone trials. They can also save drugmakers time and money in study startup and can increase data quality and efficiency through shared and reusable infrastructure.
“In a one-off, one-arm clinical trial, every time the trial is done it gets ripped up,” Tenaerts says. “The next person who wants to come in with a new treatment has to build up the sites and set up the whole infrastructure again. Part of the master protocol system is that you create this ongoing activity — where study drugs can come in and out — so you lose having to set all that study startup time aside every single time because the center is already engaged. It creates a continuous learning environment and it’s a lot more efficient.”
While the FDA’s guidance only covers COVID-19 trials, Tenaerts says she believes the door is open to expanded use of master protocols. “At CTTI, we had a lot of patient organizations come to us that were looking at the effectiveness of the clinical trial system. They were interested in learning how to do master protocols in areas that hadn’t typically had master protocols. The areas where master protocols were happening were in oncology. These patient groups asked ‘How can we do this better? What should we think about master protocols?’”
In its guidance, the FDA advised sponsors using master protocol designs to meet with the agency before making a change where a drug evaluated under a master protocol is incorporated into a trial as either background therapy or as part of the control arm. The FDA also advised sponsors to meet with them to discuss endpoint selection in cases where drugs intended to affect different aspects of a disease — such as anticoagulants and antivirals — may have multiple endpoints specific to the intervention.
The FDA said it may be appropriate, under certain circumstances and with agency concurrence, for sponsors to take a selective approach to safety data collection for repurposed drugs being studied for use against COVID-19. The agency said sponsors should also use a central IRB to review the master protocol and should appoint an independent, third-party data monitoring committee or similar entity to assess safety and efficacy data.
Read the guidance here: https://bit.ly/3eReoYY.