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How real-world evidence will help FDA develop a vaccine.
The numbers associated with the coronavirus disease 2019 (COVID-19) keep rising: in the United States alone, daily cases topped 70,000 for the first time this week, and the number of deaths exceeds 130,000. Although treatments such as Gilead’s remedesivir are helping patients recover, shortages of the drug are now problem. More treatments are needed, and what is needed most of all is a vaccine.
Several large vaccine trials are launching this month—these are giant studies, with 30,000 volunteers each. But clinical trials won’t offer all the data that scientists will examine in their quest to tame the pandemic. FDA officials, and specifically Amy Abernethy, MD, the agency’s principal deputy commissioner, have said that regulators will also use real world evidence—data from health records, registries, and insurance claims—to glean insights that can help design studies or set research priorities.
FDA has been gearing up to use real-world evidence, or RWE, for some time. In December 2018, the agency issued its framework for a series of guidance documents to speed the use of such data in the approval process.
COVID-19 adds urgency for the use RWE, said Nancy Dreyer, PhD, MPH, chief scientific officer and senior vice president, Real World Solutions, IQVIA. It’s a health crisis on a global scale, and every hour patient records are being collected that could be analyzed to offer a picture of the pandemic.
In an interview with Managed Healthcare Executive®, Dreyer discussed how RWE might be used, what questions it might answer, and even how it might be collected in the time of COVID-19.
The first difference that Dreyer noted between clinical trials and RWE is that clinical trials typically measure finer data points using surrogate markers. By contrast, she said, “In real world data, we tend to look at much bigger, cruder outcomes: are you dead or alive? Did you get admitted to the hospital? Are you on a respirator? So, the opportunities for real-world evidence in COVID are to get those clinically meaningful end points, which don’t always match your trials.”
RWE could offer researchers opportunities to create a common external control arm—which would allow all the competing vaccine candidates to compare their product against the same control. That might be challenging to convince competitors to do, Dreyer explained, “but I think it’s one of the biggest opportunities we can’t miss—particularly for vaccines,” although a common external control arm could be useful for treatments, too.
With treatments, RWE offers opportunities to examine long-term follow-up, including important quality of life questions. Remedesivir and dexamethasone might get a patient out of the hospital, but what happens next?
“You saved my life, doc, thank you,” Dreyer said. “Can I still think? Can I still have my life back as it was beforehand? It’s going to be real-world evidence that’s will give you the key to that.”
A critical use of RWE will be in post-marketing studies for vaccines, when the product is used among a more diverse population. Inevitably some patients will have reactions that were not seen in the clinical trials, Dreyer said, “because we always do.”
How RWE is gathered at this stage will be critical, she explained. Bringing everyone in for an appointment at 6 months isn’t practical. “We’re talking about millions of people,” she said.
But having a light touch method to reach people, perhaps through a text, to ask if how they are doing or if they have been hospitalized, will be important. Should all patients be asked the same follow-up questions regardless of what type of vaccine they receive? Dreyer agreed this would help.
In looking ahead, Dreyer said there will be three distinct populations with COVID-19 who should be studied: (1) patients who have been hospitalized, for whom there is an abundance of data, (2) patients in the ambulatory setting, who she said “have barely been studied,” and (3) the “silently sick at home,” which Dreyer said is a population that IQVIA is beginning to examine and collect data on.
It’s essential to have data on all three groups, Dreyer explained, especially for managed care, because fairly soon physicians will be asked to evaluate these patients and make decisions based on evidence whether they can return to work, “and there's very little information on that.”
What has COVID-19 changed about data collection? For Dreyer, it has shown that some data that is important to evaluate does not show up in the traditional measurement methods, such as a blood test. Patient-reported symptoms are very important in COVID-19. Technology has been a game-changer, too, as changes made with safety in mind could forever change clinical trials.
“Parts of the technology make it [possible] to do these decentralized virtual trials, that allow us to use in-home technologies, whether it's your pulse oximeter, or an EKG on a smartphone,” Dreyer said.“So, we'll be able to do a lot more without requiring people first to come into the health system. And then many of these tests will be able to be done without the intervention of the healthcare provider, so they can go on with their business, but be informed by these data.”