In March of this year, it dawned on health professionals and government ministers alike that the coronavirus pandemic sweeping across Europe had real potential to overwhelm the NHS. By 16 June the ambitious RECOVERY trial (based at the University of Oxford) announced that dexamethasone, a common steroid, could reduce mortality in people with Covid-19 respiratory complications by one-third. But in a world where clinical trials usually take years to conduct, how was a potential treatment discovered so quickly?
Writing for Nature, Nicole Mather, an executive board member at NHS DigiTrials, explained how the RECOVERY trial was conducted so rapidly, and how this may be broadly applied in the future to accelerate subsequent clinical trials. She said: “The RECOVERY trial had five key features which distinguished it from a standard approach.”
The first of these features is a flexible protocol which lays out the study’s design, data and regulatory requirements in just 20 short pages. The second is the rapid granting of ethical and regulatory approval. Usually, this process can take 30-60 days; the RECOVERY trial did it in nine. The third is the simple recruitment procedure, requiring patients to fill out a consent form of just two pages, and clinicians filling out a one-page bedside form. Fourthly, the RECOVERY trial utilised the NHS DigiTrial services (set up in 2019 for planning large clinical trials) to collect and process data rapidly. Finally, the results of these analyses were quickly made public, being published within a month.
So how can these features be applied to future studies to accelerate their undertaking and completion?
Streamlining the bureaucracy surrounding such trials seems a critical place to start. “We’ve gone so far towards managing risk that we’ve created layers of bureaucracy that absorb time and money, and, paradoxically, increase the risk that beneficial treatments are not tested”, Mather said. Thus, in the future, it would be beneficial to cut down the length of clinical protocol forms, patient information forms and ethical consent forms, all of which can run into thousands of words.
The RECOVERY trial also benefited from the work of HNS health-data systems, such as the NHS DigiTrial system. Further investment into such NHS data systems will speed up data collection and analysis, as only minimal bedside data need be collected, which can then be integrated with routine NHS information on treatment, diagnosis and survival.
Finally, Mather emphasised the importance of trust and transparency in a successful clinical trial. Working with institutions in which the public have confidence, such as charities or non-government organisations, will help in nurturing trust in the use of health data for research and development of care. As well as this, transparency is vital to help garner trust but also to ensure that results are clearly understood and confidently acted upon. RECOVERY was successful in “ [balancing] rapid sharing and expert review”, she said. While the clinical protocol and core documents are all available on a public website, key results of the study were made rapidly available through public announcements before journal publication. This clear communication is vital, as, within hours of this announcement, NHS hospitals were aided to adopt dexamethasone in treating Covid-19 patients.
It seems clear that a more straightforward and pared-down approach to clinical trials can greatly accelerate the rate of completion and treatment discovery, without sacrificing peer review or bypassing regulatory processes. Now all that remains to do is to apply the lessons learned from the successes of RECOVERY to future clinical trials.