From staff reports
A novel clinical trial developed by researchers at the University of Pittsburgh School of Medicine launched Thursday addresses how doctors should decide between quickly adopting new therapies, such as the anti-malarial drug hydroxychloroquine, and waiting until they are tested in longer clinical trials.
“The solution is to find an optimal tradeoff between doing something now, such as prescribing a drug off-label, or waiting until traditional clinical trials are complete,” Derek Angus, professor and chair of Pitt’s Department of Critical Care Medicine, said in a news release.
“We’ve developed a way to do that with an adaptive clinical trial model that relies on a type of artificial intelligence known as reinforcement learning to identify the best, evidence-backed therapy for COVID-19 much faster than using the traditional scientific approach.”
When COVID-19 began circulating, REMAP-CAP was rapidly adapted, as per its intent, to incorporate additional treatment regimens specifically targeting the SARS-CoV-2 virus, the release said.
The international team describes the REMAP-CAP platform in a manuscript published Thursday in the Annals of the American Thoracic Society (AnnalsATS).
REMAP (randomized, embedded, multi-factorial, adaptive platform) allows researchers to rapidly test multiple treatment approaches simultaneously at a lower cost and with fewer patients than traditional clinical trials, the release said.
The REMAP design, first described by Angus in 2015 in the Journal of the American Medical Association (JAMA), is a flexible version of what are called “adaptive platform trials,” the release said.
“Adaptive platform trials are rapidly being endorsed by the U.S. Food and Drug Administration, the Bill & Melinda Gates Foundation and others as a long-needed revolution in clinical trials,” Angus said.
“In a pandemic, doctors will not have the time to debate the pros and cons of every possible clinical trial,” Angus said.
“By building this one-stop solution at the point-of-care, we are rolling out an approach that can assure that every patient admitted with COVID-19, if they choose to, can be enrolled in the program.
“We must throw out old ways of thinking and fuse clinical care and clinical research into one extremely efficient system.”
If new drugs need to be tested, the release said, they are rolled into the platform as study amendments, rather than tested in separate free-standing trials.
Most participants will receive one, two or three of the experimental treatment options. This means that, at launch, only 12.5% of participants will be strictly assigned to the placebo arm of the trial and, within weeks, researchers expect that about 99% of patients will be receiving one or more active therapies specifically targeting COVID-19.
If one of the treatments shows early signs of better performance than the others, patients are automatically enrolled more often into that treatment option, the release said.
“This allows us to always rapidly identify which treatment works best, while keeping the number of patients needed to achieve statistical significance low,” Angus said. “It also means we get the best treatment to the most patients right out of the gate.”
The design and implementation of REMAP-CAP worldwide is supported by multiple governments and institutions, the release said.
