One of the lasting effects of the COVID-19 pandemic is likely to be the accelerated acceptance of adaptive clinical trials.
Dr. Anthony Fauci endorsed adaptive trials when he announced the effectiveness of redelivering in treating COVID-19 patients.
“The data shows that remdesivir has a clear-cut, significant positive effect in diminishing the time to recover,” Fauci said in a White House briefing April 29.
The data came from a unique type of clinical trial launched in February and sponsored by the National Institute of Allergy and Infectious Diseases where Fauci is director. The Adaptive COVID-19 Treatment Trial (ACTT) is different from classical clinical trials in that researchers can make changes in dosing, patients and other parts of the study as the data accumulates.
That’s why, not quite two months into the study, Fauci was able to declare remdesivir effective in reducing recovery time for COVID-19 patients. Discussing the trial findings up to that point, Fauci said, “What [the trial] has proven is that a drug can block this virus.”
Adaptive clinical trial design is common in testing medical devices, but much less so in testing drugs and new therapies. Those tests are almost exclusively designed as randomized clinical trials (RCT) in which subjects are divided into at least two groups, with one receiving the new drug and a second a placebo. It’s a double-blind test meaning neither the patient nor the clinical researchers know who is getting what. Once underway, only in the rarest of situations can the process depart from the trial’s original design.
Though considered the gold standard for testing the efficacy and safety of new drugs, the RCT design has been criticized for its cost, duration and inflexibility. As long ago as 2004 the Food and Drug Administration announced a Critical Path Initiative to accelerate drug development. “Modernizing Clinical Trial Designs and Strategies” was one of the programs.
At the end of last year, the FDA issued an industry guidance for pharmaceutical and bioscience firms “on the appropriate use of adaptive designs for clinical trials.”
The guidance notes,
“Adaptive designs can provide a variety of advantages over non-adaptive designs. These advantages arise from the fundamental property of clinical trials with an adaptive design: they allow the trial to adjust to information that was not available when the trial began.
While the ACTT, first launched at the University of Nebraska Medical Center and now involving 68 sites, and other adaptive COVID-19 trials now underway are showing they can deliver results, adaptive trials are unlikely to any time soon – or ever — become the new standard for drug testing.
Dr. Adams Dudley, a drug safety expert at UC San Francisco, told the Los Angeles Times, it’s risky to allow companies with a financial stake in the outcome to change study rules during a trial. However, in a crisis like the current COVID-19 pandemic, Dudley said randomized clinical trials take too long.
Noted the Times, “With thousands of people dying every day of COVID-19, the deliberate pace of this gold standard research may not be the best way to end the crisis quickly.”