Pandemic Perspectives: US FDA, NIH Tried To Be Flexible To Keep Rare Disease Trials Going
Executive Summary
Both federal agencies extended grants to help investigators adapt to the changes mandated by the COVID-19 pandemic.
Rare disease clinical trials in the start-up phase seemed to suffer the most from the coronavirus outbreak, even as the US Food and Drug Administration and other funders tried to help investigators navigate the pandemic with minimal upheaval.
The FDA Office of Orphan Products Development said 5 March during the agency’s Rare Disease Day conference that 79% of clinical trials and natural history studies supported by its grants reported some impact from the COVID-19 pandemic.
Katherine Needleman, director of OOPD's clinical trials and natural history grants programs, said the FDA in some cases gave additional funding or allowed investigators to make changes to accommodate pandemic necessities.
Pandemic Perspectives
One year on from the World Health Organization declaring COVID-19 a global pandemic on 11 March 2020, editors across Informa Pharma Intelligence publications are taking a closer look at its impact and possible lasting implications for the biopharma and medtech industry.
“OOPD continued to allow for flexibility for the funded studies as well as for future funding,” she said. “OOPD also offered administrative supplements to address unexpected increases in costs in these ongoing trials. We saw several ideas that would help these ongoing studies be successful, as well as provide the ability to complete the trial.”
Needleman said the agency allowed grants to support additional personnel, as well as less centralized testing and more communications tools, such as cloud-based imaging platforms, due to travel restrictions.
In addition, the FDA established a forum for orphan grantees to meet and exchange ideas for dealing with problems presented by the pandemic. A workgroup is evaluating and documenting the discussions and intends to publish a paper on the actions taken and lessons learned for rare disease research.
Chris Austin, director of the NIH National Center for Advancing Translational Sciences, said during the conference that “certainly the research ground to a halt” at the National Institutes of Health, including natural history and interventional studies. Staff tried to help keep trials going and allowed grantees to regain time lost due to lockdowns, he said.
“We have tried at the NIH to the degree that we can without additional funding to extend grant periods, training periods for trainees, to make up for the six months to a year that all of them have lost,” Austin said.
However, the damage to the clinical trial landscape remains. In many cases, study personnel lost their jobs or were forced to leave, Austin added.
“It’s not just a matter of time, it’s a matter of people and expertise and losing people semi-permanently because they didn’t have a way to support themselves,” he said. “We realize we’re going to have some rebuilding to do.”
Indeed, while some issues may already be apparent, much of the pandemic’s impact on clinical research may not be known until after it is over. (Also see "Full Extent Of Clinical Trial Damage May Be Unknown Until Pandemic Ends, CBER’s Peter Marks Says" - Pink Sheet, 13 Oct, 2020.)
Austin also is hoping the clinical trial enterprise retains many of the innovations that emerged and does not return to the pre-pandemic status quo. (See sidebar.)
Study Enrollment Delays A Common Problem
By far the most common problem flagged by orphan disease investigators, 63%, was delayed study enrollment. Thirty-nine percent of grantees required protocol modifications and 32% added virtual capabilities. One-quarter of grantees experienced what were termed “budget implications,” 21% reported travel issues and 18% experienced product delivery or specimen collection issues, according to FDA data. (See chart below.)
OOPD said 39% of clinical trials and natural history studies supported by its grants were suspended and 25% experienced study or grant completion delays.
Rachel Sher, National Organization for Rare Disorders VP of policy and regulatory affairs, said that an informal survey of its corporate council members last year revealed more than half were forced to postpone enrollment of at least one clinical trial and 48% had to adapt ongoing trials to the pandemic.
Sher said 8% of sponsors were able to conduct trials as usual. Studies that were ongoing when the pandemic emerged were most likely to continue.
“Rare disease studies that were in start-up and enrolling phases had to make adjustments to continue and they were more likely to have suspended their study activities,” she said.
Once the pandemic began, the FDA issued guidance with recommendations to keep trials going with minimal disruption, including employing video conferencing and allowing alternative sites for some lab and imaging requirements. (Also see "For COVID-Impacted Studies, US FDA Loosens Video Conferencing But Tightens Home Infusion Guidance" - Pink Sheet, 12 May, 2020.)
The story continues after the chart…
Fall Deadline for Orphan Grant Applications
With orphan diseases a growing focus of drug development given the available incentives and price durability, OOPD’s grants programs also are gaining more attention.
The Orphan Products Grants Program has an annual budget of nearly $18m. About $15.5m supports clinical trials and $2m funds natural history studies.
The next receipt date for OOPD clinical trials grants is 6 October. In addition to the typical proposals, the FDA is offering a separate optional demonstration project for which proposals with innovative collaboration, patient recruitment and retention strategies, and data modeling or simulation methods that could serve as models for future rare disease drug development will be considered, according to the funding announcement.
The FDA and industry remain interested in modeling and simulation to speed drug development. The agency has proposed expanding the program as part of the prescription drug user fee reauthorization, but an agreement has not been reached. (Also see "Patient-Focused Drug Development, Complex Trial Design May Not Get More Funding In PDUFA VII" - Pink Sheet, 4 Mar, 2021.)