Rules for Clinical Trials in a Pandemic
A study out of Britain shows how to learn more, faster about promising coronavirus treatments.
A new study finds that adding a simple steroid to the treatment of severe Covid-19 cases can significantly reduce deaths. That’s another milestone in the battle against the virus. It shows a path for reducing Covid deaths faster through medical innovation and for keeping the health-care system from being overwhelmed as the epidemic spreads.
The U.S., unlike Europe and Asia, seems to have decided not to crush the virus but try to reduce its spread to a controllable level. The 30,000 cases diagnosed each day probably represent no more than 20% of the total infections. It’s a lot of virus, but mostly manageable, for now. It won’t stay that way.
Death rates are down, partly because older Americans are protecting themselves. More new infections are among younger people less likely to have bad outcomes. But come fall it will be hard to keep infection rates down and isolate older Americans and those with serious health risks. Covid spread will collide with seasonal flu.
The novel coronavirus won’t simply disappear. By virtue of its biological features, we can expect it to infect about 60% of a population before receding—still a long way off. Effective vaccines would stop it, but until that happens, the best bet is for most Americans to heed practical measures to reduce risk for themselves and close contacts, while physicians use innovative methods to mitigate severe cases and shorten hospitals stays.
Which brings us to the new study on the steroid. The preliminary report from a British trial called Recovery is that dexamethasone can reduce death rates by a third among Covid patients requiring mechanical ventilation and 20% in those needing oxygen. The finding came from one of the world’s largest continuing randomized, controlled trials for coronavirus treatments. Conducted in hospitals across the U.K., Recovery enrolled more than 11,000 patients randomized to receive usual care or one of six possibly effective treatments. It’s continuing to enroll more patients and test more treatments at a much faster pace than smaller trials.
Recovery, an acronym for Randomised Evaluation of Covid-19 Therapy, is a model for learning faster about what works. It’s a practical trial that assigns patients to different treatments at random, with data collection limited to the most important measures of disease severity and outcomes, making participation easier. The protocols of trials in the U.S. are more elaborate, which means less enrollment and results take longer.
Public-health authorities in the U.S. aren’t supporting the Recovery model, viewing it as insufficiently rigorous because it didn’t collect information on all of the variables that could influence outcomes. But complex studies are often impractical in the setting of an epidemic, where clinicians are hard pressed to carve out time from crisis medical care to track and record hundreds of required variables. The British approach makes it manageable to learn what works in many more hospitals.
The Food and Drug Administration recently took steps to expand the use of real-world evidence—derived from electronic data on the treatments and outcomes of the rising number of Covid patients—to help assess other drugs such as blood thinners and plasma derived from recovered patients. But without randomized trials, it’s hard to determine what works. Thousands of hospitalized patients received hydroxychloroquine before randomized trials revealed that it didn’t help. Thousands have received convalescent plasma. While this seems to help, no one is sure.
In the 1980s, straightforward trials enrolling large numbers of acutely ill heart-attack patients helped drive down heart-attack deaths. It’s now even easier to capture this kind of data electronically. More-detailed randomized studies like those in the National Institutes of Health trial network are also necessary, especially for new drugs, and can complement expanded practical studies.
Some existing U.S. clinical trial networks have tools that other hospitals could adopt to participate. Health-care payers like Medicare should pay a little more for evidence collection when they do; it’s more efficient than continuing to pay for treatments like hydroxychloroquine without knowing whether they work. The same larger networks could also expand the evidence available on new drugs such as the antiviral remdesivir—whether the length or timing of treatment matters, for example.
The U.S. appears consigned to high Covid case levels and health-care systems that will continue to be under threat. We owe it to all of the patients who will be hospitalized to use this unfortunate reality to help providers make the best treatment decisions possible.