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Pink Sheet – Operation Warp Speed Had Trouble Enrolling Patients In COVID-19 Therapeutic Research

Pink Sheet – Operation Warp Speed Had Trouble Enrolling Patients In COVID-19 Therapeutic Research

Executive Summary

US FDA Acting Commissioner Woodcock says there is ‘a long list’ of lessons learned in the OWS therapeutics group, noting trial bureaucracy and the lack of resources and support for community centers.

While Operation Warp Speed advanced several COVID-19 vaccine candidates, it faced numerous hurdles on the therapeutics side, including the ability to enroll patients in clinical trials.

“We had tens of thousands of people dying and we couldn’t enroll patients because we were relying on networks that had been stood up before and we just had a limited number of sites and we had a lot of … competition for patients,” US Food and Drug Administration Acting Commissioner Janet Woodcock, who headed the OWS therapeutics group, said.

Woodcock offered a glimpse of what went on behind the scenes of Operation Warp Speed at a 9 April webinar on modernizing eligibility criteria for clinical trials sponsored by the American Society of Clinical Oncology and Friends of Cancer Research. OWS was established by the Trump Administration to accelerate development of COVID-19 vaccines and therapeutics.

Woodcock said the community hospitals affiliated with the networks could not enroll patients because they hadn’t received training and did not have research or study personnel.

“So, we have to think of ways that you can enable that because it’s not like community care is totally opposed to participation. It’s just they aren’t resourced and supported, they don’t get trained and so you don’t have those opportunities,” Woodcock said.

‘Too Much Trial Bureaucracy’

Moderator Edward Kim, physician-in-chief at City of Hope Orange County, a cancer center in California, asked what lessons had been learned from COVID-19 that can be implemented. Woodcock cited changes in the informed consent process, remote, no-touch visits through telemedicine, and use of electronic health records.

“If we can move to those innovations we’re going to help those practitioners out in the community participate because there will be fewer forms,” she said.  But “we were really impeded and we still are by too much trial bureaucracy and unnecessary repetition of all kinds of things.”

Woodcock noted the lack of central coordination and duplication in therapeutic studies during a Milken Institute webinar last month. (Also see “Early ‘Scattershot’ Approach To COVID-19 Therapeutic Research Generated Little Actionable Data” – Pink Sheet, 1 Apr, 2021.)

At the ASCO/FOCR event she said she and others in the OWS therapeutics group are putting together the lessons they learned. “It’s going to be a long list,” she stated.

Real-World Evidence And Master Protocols

National Cancer Institute Director Norman Sharpless, who participated in the discussion with Woodcock, noted one lesson had been how the use of real-world evidence can inform clinical practice. (See sidebar).

Woodcock cited FDA’s experience with the COVID-19 Evidence Accelerator, a joint project of the Reagan-Udall Foundation and the Friends of Cancer Research, to see how real world evidence performs on different critical questions and treatments.

She said another lesson is that most of the trials that have provided data in the pandemic have been master protocols. She noted that one great advantage of the protocols is that they can be run seamlessly without repeatedly standing trials up and shutting them down. Woodcock cited her involvement in RECOVERY, REMAP-CAP, I-SPY COVID and the ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trials, the latter of which was launched by the National Institutes of Health.

“The only beef I have about those is the reach into the community I think wasn’t what it should have been,” she said. “But in fact, that’s an innovation that I think has come of age.”

Asked what the most urgent goal for clinical trials is in the next year, Woodcock said the most urgent thing to do is to figure out how to integrate research into clinical practice and start working on that.

“We’re going to reach diverse participants best by engaging the practitioners that they usually see, the people taking care of them in the community. And if we’ve contracted the research enterprise away from the clinical care enterprise, we have to put it back into clinical care,” she said. “This is a real inflection point right now because we have seen both the impact of COVID, a pandemic, on our population and also in the trials that have been done and not done in the United States.”

Going ‘A Little Bit Further’ in Clinical Trial Eligibility

The webinar noted the recommendations made by ASCO and FOCR to broaden eligibility criteria in cancer clinical trials with the goal of making them more accessible to patients. (See sidebar for related story.) Sharpless said exclusion of patients based on brain metastases, HIV status, and renal insufficiency is bad for patients and for research progress.

Woodcock agreed, adding “we need to go a little bit further.” She suggested including patients with serious morbidities in the evaluation of a drug’s safety.

“We can run forms of trials that have people with renal failure or people with other serious kinds of morbidities. They don’t have to count in the major efficacy, but they will contribute to safety and they will tell us information about people we’re going to treat in the real world,” she said. This would “open scientifically the main trial as much as possible for those who will contribute to the evaluation and then do safety studies in other populations who are undoubtedly going to need that drug” if it turns out to be safe and effective.…