Too Many Poorly Designed Trials Led to the Lag in Covid Therapeutics: FDA
(Thursday, March 4, 2021)
In the last 12 months, more than two thousand Phase 2 and 3 clinical trials were launched worldwide to evaluate various therapeutics for COVID-19, containing 2895 individual treatment arms aiming to recruit more than 500,000 patients. However, an FDA analysis showed that only 5% of these trials were randomized and adequately powered, accounting for about 26% of the total patient enrollment in Covid therapeutic clinical trials, meaning 3 out of 4 patients enrolled in clinical trials which would not be expected to yield actionable information by the FDA. This wasteful use of available resources likely led to the overall delay in getting a reasonable therapeutic to the patients. To date, there is only one drug, remdesivir, approved by FDA for treating Covid-19, which is limited to clinical setting and is modestly effective. In the months of March and April 2020 alone about 1000 clinical trials were launched worldwide to evaluate Covid therapeutics. But these were not all for unique products. There was a great duplication of effort with multiple small trials studying similar interventions in similar populations. By July it was becoming clear that too many trials were hurting the efforts to find a therapeutic, rather than helping. The onset of the pandemic created urgency among the regulators and governments worldwide to develop products to prevent, treat and diagnose the disease leading to a huge influx of public and private money into these efforts. For many developers, it presented an opportunity; jumping in the hunt for Covid therapeutics could not only be the way to test ideas that otherwise would be shunned, but also lead to new money. Afterall, it did work for vaccine developers like Moderna and Novavax. However, unlike vaccines, Covid therapeutics ended up becoming a lesson for future rather than an example of what could work in an emergency. The FDA and other regulators had to hence deal with an onslaught of new competing clinical trial applications and the Agency was left with the hard job of allowing many of these trials to proceed despite knowing the limitations of these trials. Many trials were submitted as Phase 2 and Proof-of-concept (POC) studies which have a lower threshold for clearance to proceed. Under the law, FDA cannot reject a proposed clinical trial without a robust rationale for rejection. This analysis sheds a cruel light on the regulatory limitations for developing much needed therapeutics for deadly diseases, something we have seen with cancer and neurological disease therapeutics as well where over-crowing of the field with poorly designed trials and duplicative efforts delays new drug approvals. The FDA assesses that it needs two tools to avoid that: First, a robust screening mechanism to select promising well-justified products over others, and second, allowing trials that would lead to actionable information over exploratory ones. However, it is not easy to implement. Without major regulatory overhaul, it is not obvious how FDA can do that when a given trial meets the threshold for approval but is duplicative of others. FDA is not allowed to pick winners among competing products, and for good reasons. And with the pandemic rapidly coming under control, the pressure for creating a Covid therapeutic will likely fade, meaning the push to make tough regulatory changes may not exist. The FDA article points fingers at the system’s limitations, but solutions are not easy.

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AUTHOR               

 Dr. Mukesh Kumar
​ Founder & CEO, FDAMap

 Email: mkumar@fdamap.com
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