DIA 2021 Annual Meeting: FDA Flags Master Protocols, Decentralized Trials as Focal Points
From the lessons learned in the COVID-19 pandemic, the FDA intends to push for greater use of master protocols, decentralized trials and digital health technology moving forward, said Acting Commissioner Janet Woodcock.
Woodcock said the FDA recognizes that master protocols such as RECOVERY, the ACTIV trials and the REMAP-CAP trial, among others, performed remarkably well and yielded the greatest amount of actionable data, especially for therapeutics.
“The issue with master protocols is they take a while to set up because they’re more complicated, but once they get up and running they can evaluate multiple agents efficiently, and you have kind of an anchor of understanding that trial network, how it’s performing, what you’ve seen already,” she said. “There’s a tremendous amount of validity that starts accruing as they run through agents and look at them.”
Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni called the pandemic a “turbocharge” for the use of master protocols. She noted that while the agency’s May guidance on the subject is still technically COVID-19 guidance, she expects and hopes that master protocols will be adopted to a much greater degree into the future.
“[I hope] that some of the infrastructure that we have put in place to run these protocols, clinical trials and coordination and so on, will actually remain a standing infrastructure or an infrastructure we can sort of reactivate as needed and might be deployed in other areas of unmet medical need,” Cavazzoni said.
Master protocols have seen a surge in acceptance as a result of the COVID-19 pandemic, which has shed a light on the need for “more structured and sustainable approaches” to evaluations of trials, according to a recent paper by lead author Jay J H Park and other researchers that was published in The Lancet.
Cavazzoni highlighted rare diseases as a potential area for master protocols, an area that Center for Biologics Evaluation and Research (CBER) Director Peter Marks seconded. Woodcock, Cavazzoni and Marks spoke at the closing session of the 2021 DIA annual meeting. Marks said that the use of platform trials, which may help to reduce the administrative burden involved in creating multiple protocols, is “really something [the FDA] can hopefully take forward.”
Master protocols may also have potential beyond rare diseases as a way of making drug development more efficient, Cavazzoni said.
Additionally, they could help to answer critical questions about treatment policies for most diseases, according to Woodcock, who added that she will push for the use of master protocols conducted in the community as opposed to the ivory tower of research in the hopes of making trials more inclusive.
“Those questions are usually answered by expert opinion, not data. I think … clinical research is part of medical services that should be offered to people,” she said. “In fact … only about 8 percent of cancer patients are offered participation in clinical trials, yet today for many cancers, that’s going to be the best quality of care that you can get. I really think we need to examine that and figure out how we need to move out into the community. I think master protocols … and many of the remote tools we can use now, hopefully we can decrease the bureaucracy and so forth to get those really started and get the support that’s needed.”
The initiative to make trials more inclusive will be bolstered by upcoming CDER guidance on conduct for decentralized trials and the use of digital health technologies to remotely collect data, Cavazzoni said. Decentralized trials have been integral to keeping clinical research afloat during the pandemic, with the restrictions imposed on travel and in-person gathering, and the FDA is intent on taking advantage of what it’s learned throughout the crisis regarding decentralized trials and digital health tools.
“These tools are going to be essential in bringing more remote sites or community-based sites into clinical trials,” Cavazzoni said. “We could actually view access to clinical trials as a health equity issue.”
To Marks, the pandemic has shined a spotlight on the importance of working toward more pragmatic and inclusive trials. Having trials that can be conducted in the community through the use of remote assessments and other measures will help trial populations become more diverse and ultimately lead to better clinical evidence, the CBER chief said.
Dawn Anderson, a managing director for Deloitte Consulting’s life sciences practice, said that focus groups and surveys indicate that patients greatly enjoy the flexibility of decentralized trials. The trend of increased decentralized trial use, spurred by the pandemic, could very well become a new normal after the crisis is deemed to be over, she said.
“Two or three years ago, I could have pulled all my large global pharma clients and asked them how quickly they’d be doing decentralized trials, and they would have told me within the next five to six years,” said Anderson. “With COVID, all of a sudden, almost all of them had to put in place decentralized capabilities almost overnight, and patients may not be willing to return to traditional site visits when this pandemic is over.