CDER's Janet Woodcock: Pharma, regulators have lessons to learn from Covid-19
When pharmaceutical companies, health care leaders and regulators finally get a chance to debrief and pull lessons learned from the coronavirus pandemic, a chief takeaway may revolve around the many missed research opportunities. However, learnings from Covid-19 may one day lead to novel trial design and increased cooperation among these players promise a better path forward when speed and safety need equal consideration. This message was among many shared by a leading regulator in a 9 November audio interview with editors at the New England Journal of Medicine (NEJM).
Janet Woodcock, the longtime director of the FDA’s Center for Drug Evaluation and Research, stepped away from that role to participate in Operation Warp Speed (OWS), the government’s coronavirus treatment and therapeutics accelerator. In conversation with NEJM’s editor-in-chief, Eric Rubin, deputy editor Lindsey Baden, and executive managing editor Stephen Morrissey, Woodcock shared her unique perspective as a regulator-turned-drug developer during the pandemic.
The problem with an EUA
Though emergency use authorizations (EUAs) are appropriate when a novel disease like Covid-19 strikes – in the case when, said Woodcock, “our hands are empty” – the early deployment of a therapy or vaccine into the community means “that it can be difficult to continue to do the research you need to do,” she said.
Ideally, the deployment of each EUA should have been a research opportunity: “They should have randomized the first patient…We’d be in a better situation of understanding” more about which populations benefit and what the true effectiveness is of the therapies authorized to date, she said. The RECOVERY trial in the UK, an adaptive, real-world randomized trial that is yielding ongoing information about Covid-19 antivirals and therapeutics, is an achievable example of how to collect high-quality data during clinical care.
When is there enough evidence gathered from these sources to warrant the issuance of an EUA? “To your question, this is a classic dilemma for people with very serious illness, which is how much certainty do you want to have, versus the peril of a mortal illness,” noted Woodcock.
What trials are occurring worldwide are disaggregated and small, noted Woodcock, with the current estimation of OWS being that only about 5% of therapeutics trials will yield evidence high enough for publishable studies. OWS has attempted to overcome some of the heterogeneity and data quality issues by forming a “data lake” for big data analysis.
In regular International Coalition of Medicines Regulatory Authorities (ICMRA) calls involving regulators for up to 50 countries, Woodcock said, “I’ve presented the data on the worldwide trials and the lack of actionable trials, and I think everyone is on the same page about this and there will be an opportunity for … the medical ecosystem worldwide to come together and say, ‘We can do better.’ We can have a more coordinated and cohesive response.”
Going forward, hope for cooperation and innovation
Asked about the best way for stakeholders to be well positioned in terms of infrastructure and scientific approach the next time a rapidly spreading infection challenges the globe, Woodcock pointed to the promise of adjusting clinical trial design. “For a long time, I’ve been a proponent of master protocols and platform trials,” she said. “I think we need to have things like that set up and ready to go. They can certainly build really valuable information about standard of care during the pandemic,” she said. “And we also need some agreement amongst investigators.”
What’s more, though government needs to take the lead in moving trials along, it’s vital that pharmaceutical companies participate as well. Academic-led trials are ideal in that they are freer from potential conflicts of interest, but academic medical centers lack infrastructure to run large, well-designed trials at speed, said Woodcock. When researching a common illness like Covid-19 during a pandemic, there is the additional problem that “many of these patients are in the community, so they don’t have an opportunity to participate in trials,” she noted. The reach that pharmaceutical companies can achieve with contract research organizations can overcome some of these hurdles.
“I think the problem right now is academic trials are felt to be slow and clunky,” and often have data collection issues related to slow accrual and low numbers. Speaking somewhat tongue in cheek, Woodcock said she’s adopted a quote from epidemiologist Martin Landry and dubbed it “Landry’s Rule”: “The number of patients enrolled is inversely proportional to the number of professors.”
At OWS, said Woodcock, “We are leveraging the academic networks, but we’re trying to bring in a tremendous amount of infrastructure support,” though even with all the support OWS has afforded, there have still been problems with slow site activation and enrollment, she acknowledged.
Asked about her perspective now that she’s taken off her regulator hat and is seeing pharmaceutical development from the other side of the fence, Woodcock said, “I also appreciate from this side the pressure the companies are under to get things done, and get things out there, and how there’s constant pressure here that a lot of people don’t understand; they think we should just have these therapies out there.”
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.