Woodcock Warns Research Apparatus Could Be Overwhelmed If Coronavirus Trials Don’t Use Master Protocols
Executive Summary
CDER Director Janet Woodcock says researchers need to embrace pragmatic trial designs and compare multiple treatments at the same time rather than employ separate development programs.
Sponsors soon may have no choice but to develop master protocols and similar trial designs for coronavirus treatments, as there now are concerns there may not be enough researchers to handle the workload.
Janet Woodcock, director of the US Food and Drug Administration’s Center for Drug Evaluation and Research, said on 23 April that the nearly 1,000 inquiries and proposals for coronavirus treatments the agency has received is “a rather overwhelming amount in such a short time.”
Woodcock indicated that the clinical research apparatus may run out of capacity to handle the increasing amount of coronavirus work if development continues without more collaborative efforts.
“Although we may not run out of patients unfortunately, we may run out of research personnel and time availability to do this in this way, having separate development programs,” she said during a Clinical Trials Transformation Initiative webinar on the coronavirus clinical trial design landscape and best practices for ensuring patient safety and reliable results.
Janet Woodcock
The comments were a plea for the industry to use platform trials, master protocols, pragmatic and other designs that can test multiple potential coronavirus treatments at the same time, “particularly for all the repurposed agents that are not going to need a lot of early work,” Woodcock said.
“Then we can have common control groups,” she added. “You could use adaptive randomization because part of this early phase really ought to be to eliminate the less promising agents and to pick out the more promising agents and move them forward into more extensive evaluation.”
Indeed, the pipeline of potential coronavirus treatments and vaccines is substantial. The FDA reported that there are 72 active clinical trials of therapeutic agents and another 211 development programs for therapeutic agents in planning stages as of 19 April. Both numbers have jumped substantially in a matter of weeks. (Also see "US FDA Greenlighting Dozens Of New Trials For Coronavirus Therapeutics" - Pink Sheet, 20 Apr, 2020.)
Agency officials also are trying to complete protocol reviews within 24 hours if possible. (Also see "US FDA Coronavirus Response Features Three-Step Triage Process For Inquiries" - Pink Sheet, 15 Apr, 2020.)
The Pink Sheet coronavirus pipeline tracker includes a list of treatments and prophylaxis products in development.
Standardized Measures, Master Data Monitor Envisioned
Woodcock and other presenters during the event also advocated for the use of randomized and blinded clinical trials in coronavirus research to ensure patient benefit and safety results are clear.
John Marshall, a professor at the University of Toronto and a member of the World Health Organization Clinical Characterization and Management Working Group, also argued for standardized data measurement across the various trials. He said many researchers around the world are asking the same questions about coronavirus, adding that some may have been answered already.
“The question is how do we pool data across trials so we can glean those answers more rapidly,” Marshall said.
Marshall said a standardized set of basic clinical measures is being developed so trial results can more easily be pooled and compared. He added that the group is considering creating a master data monitoring committee to allow the heads of DMCs for the numerous clinical trials to meet and share interim analyses or other early data and communicate potential safety or efficacy signals sooner.
Woodcock also said the FDA soon will release guidance offering general thoughts on protocols, endpoints, populations and trial designs assessed to date. But she warned that the guidance will be high-level because the agency does not have much experience with completed clinical trials and to date has no successful studies.
Woodcock also reminded listeners that the clinical trial infrastructure needs a substantial upgrade, including the ability to pull trial data from electronic health records, rather than requiring separate case report forms. The message is one she has been promoting for years. (Also see "Reliance On ‘Digitized Paper’ Is Slowing Drug Development – US FDA’s Woodcock" - Pink Sheet, 14 Nov, 2018.)
Limiting Researchers’ Patient Contact Essential
Aside from increased efficiency, clinical trial conduct improvements also can better protect health care workers fighting coronavirus. Woodcock said the FDA wants to minimize the number of instances that health care workers must interact with coronavirus patients.
“Even informed consent has to be re-thought in an era where you don’t want to be passing papers around amongst various parties,” she said.
As the FDA is pushing for increased efficiency and transparency with clinical trials, the agency also is working to increase assessment speed. FDA officials expect to be watching clinical trial results in real-time in order to make decisions as soon as possible, similar to the Real-Time Oncology Review program. (Also see "CDER’s Woodcock On COVID-19: Missed User Fees Unlikely, But Some Work Will Be ‘Set Aside’" - Pink Sheet, 31 Mar, 2020.)
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