Streamlining the Virus Fight

The success with dexamethasone was the first time that a drug had been shown to help reduce the risk of death from COVID-19 in a randomized controlled trial (RCT). World Health Organization Director-General Tedros Adhanom Ghebreyesus said it gave the world “a much-needed reason to celebrate.” Two former US Food and Drug Administration Commissioners, Scott Gottlieb (whose interview with the Brunswick Review you can read here) and Mark McClellan, wrote in an editorial in The Wall Street Journal that it showed “how to learn more, faster about promising coronavirus treatments.”

RCTs are the gold standard for testing medicines because they remove biases by randomising patients to received either a drug or a placebo. But they need large numbers to work and often it takes many months to recruit the thousands of patients needed, especially if studies are complicated and investigators are asked to assess multiple medical parameters.

The extraordinary circumstances of the pandemic called for extraordinary measures to streamline procedures and deliver results fast and RECOVERY proved an object lesson in how that could work. It is a notion that may well have resonance for policymakers and company executives looking back on their own handling of the crisis.

“I think what we have been able to demonstrate is that trials can be simple and simple trials can provide really important answers,” said Haynes. “It may be a bit counterintuitive, but I hope we have persuaded people that actually collecting 10 times less information on 10 times more people can sometimes be hundreds of times more informative.”

By keeping the trial protocol simple and not over-burdening doctors with demands for lots of data about each patient, the researchers made life easier for hospitals. That encouraged widespread participation and the trial ended up involving 176 hospital sites across Britain—essentially every acute care facility in the country. In all, it recruited more than 12,000 patients, or around one in six of all Britons admitted to hospital with COVID-19.

The centralized National Health Service certainly helped expedite the work and the National Institute for Health Research also provided vital support to facilitate a rapid nationwide takeoff. Other healthcare systems, by contrast, are far more fragmented—notably so in America. Nonetheless, Haynes and his colleagues believe that the lessons of RECOVERY could still be usefully applied in other countries if there is the right level of organization. In fact, the WHO is trying something similar at the international level with the SOLIDARITY trial, which is comparing a variety of treatment options to standard care.

As in many other fields, the story underscores the importance of learning from a crisis. In the case of medicine that means taking the opportunity to conduct scientifically rigorous experiments when offering treatments to patients that may or may not work.

But the streamlined approach to running clinical trials could also have implications for drug development outside COVID-19. Across many diseases drug trials have been getting increasingly expensive, complex and slow in recent years. The result has been a huge inflation in trial costs, with some studies now costing hundreds of millions of dollars. By contrast, the super-fast RECOVERY trial had a grant of just £2.1 million.

“There are lessons to be learned outside a pandemic situation. If you could reduce the cost of trials tenfold, then you could afford to test 10 times more drugs,” said Haynes.

At its peak, the Oxford trial was recruiting 400 to 500 hospital patients every day. The rate has since fallen back to single figures, which means that enrolling enough patients to get meaningful results from the other arms of the trial will take some time. The study is also evaluating the anti-inflammatory drug tocilizumab, the antibiotic azithromycin and convalescent plasma taken from people who have had COVID-19.

The relative lull in new infections over the summer has given Britain’s healthcare system time to recuperate. But Haynes and his colleagues are not resting on their laurels. Rather, they are preparing to ride any disease resurgence and to test more potential treatments, including experimental monoclonal antibodies therapies now being developed by several pharmaceutical companies.

“We haven’t switched anything off. If there is a second wave, we are ready to put our foot back on the accelerator and investigate further drugs and answer more questions.”

--

Ben Hirschler is a Senior Advisor based in Brunswick’s London office and a former global pharmaceuticals correspondent for Reuters.

Illustration by David Plunkert.