FDA is using real-world data to better understand and answer questions about potential COVID-19 therapies, and remdesivir is the next therapy in the spotlight. Through its real-world evidence public-private partnership, the COVID-19 Evidence Accelerator, the agency and its partners assessed hydroxychloroquine, and the partnership soon will apply a similar set of questions and analyses to remdesivir, which has become the standard of care for COVID-19.
Remdesivir is currently available as a coronavirus therapy under an emergency use authorization from FDA. The drug’s manufacturer, Gilead, filed for full approval with FDA on Aug. 10.
The COVID-19 Evidence Accelerator, an initiative spearheaded by the Reagan-Udall Foundation and Friends of Cancer Research, has two focus arms: the Diagnostics Evidence Accelerator and the Therapeutics Evidence Accelerator.
Launched in April, the accelerator comprises health data aggregation and analytics experts from academia, government and private-sector organizations who gather and analyze real-world data, and attempt to rapidly answer key research and data questions about COVID-19 treatments and response.
The accelerator features parallel analysis workgroups — multiple teams of experts and organizations answering the same questions in parallel under a master protocol.
The parallel analysis project started with one key question: “How can real-world data improve our initial understanding of safety and effectiveness of therapies used for COVID-19?” From there, several other key questions were identified. The list of questions continues to grow, FDA Principal Deputy Commissioner Amy Abernethy said during DIA’s COVID-19 Evidence Accelerator webinar on Tuesday (Aug. 11).
“First of all we need to understand the epidemiology of COVID-19. We need to know predictors of patients at risk for the development of severe disease. We need to understand general outcomes such as mortality. That’s just the starting point. There are a number of critical questions that end up on our prioritized research list,” she added.
Other priority research topics include: treatment pattern studies; treatment impact studies, including safety and potential effect of treatments; understanding real-world performance of diagnostics; thinking about specific vulnerable populations and subpopulations like pregnant women; and thinking about how to plan for the future.
During DIA’s webinar on Tuesday, officials leading the partnership described their initial analytical work on anti-malarial hydroxychloroquine, which is FDA-approved to treat lupus and prevent malaria. The Evidence Accelerator will apply the same questions to remdesivir, Susan Winckler, CEO of the Reagan-Udall Foundation, said.
FDA granted an EUA to hydroxychloroquine for use against COVID-19 in March, after the drug was widely touted by President Donald Trump and others in the administration as a potentially game-changing coronavirus treatment.
After months of scrutiny and criticism from experts and lawmakers, the agency revoked the EUA when clinical trial data revealed the drug had little to no effect against the disease. FDA had also noted multiple times that there were reports of serious cardiac-related adverse effects associated with use of hydroxychloroquine, and warned that patients should not use the drug in outpatient settings.
In their first set of questions for the first stages of the accelerator, parallel analysis teams started out analyzing data on hospital patients with COVID-19 who were treated with hydroxychloroquine, with or without azithromycin, or who received neither drug, Jeff Allen, president and CEO of Friends of Cancer Research, explained. They also looked at the natural history of the disease.
The groups first characterized the COVID-19 patient population at baseline. Then they looked at patients who received hydroxychloroquine, including at what point in the trajectory of their illness they began receiving treatment, which patients were receiving the therapy combinations versus the individual drugs, and the different doses that were delivered.
Teams then characterized the safety signals that were observed with different interventions, especially among different subpopulations.
Finally, the groups compared observations about some of the long-term effects of different drugs.
Overall, the Evidence Accelerator teams saw that treatment regimens with hydroxychloroquine show no evidence of benefit, Allen said. But it was unclear whether the drug resulted in detrimental health outcomes.
“This is a subject for ongoing work. These analyses are still being conducted by our data partners, but we’re really grateful for not only them contributing their data to this important initiative, but most importantly, contributing their expertise,” Allen said.
The Evidence Accelerator will next assess remdesivir in hospitalized patients, and will expand its research into the natural history of coagulopathy, which will be part of the third set of questions posed to the parallel analysis teams.
Throughout its analysis of hydroxychloroquine, the Evidence Accelerator was able to identify some challenges and hopes to learn from that in its next analysis.
For instance, there were challenges with identifying outcomes, like mechanical ventilation, which is inconsistently coded in electronic health records. EHR data also is oftentimes not structured, according to Carla Rodriguez-Watson, scientific director of the Reagan-Udall Foundation’s Innovation in Medical Evidence Development and Surveillance.
Also, in the early days of the pandemic, there weren’t set diagnosis codes and many people weren’t getting tested. So, coding algorithms to identify those patients were challenging, Rodriguez-Watson added.
It was also challenging to identify COVID-19 medications, as not all of them are standard drugs specifically for COVID-19, Rodriguez-Watson said. That could also pose a problem for drugs like remdesivir that have been used in clinical trials.