A viewpoint in the Journal of the American Medical Association has offered potential solutions to modifying ongoing randomised clinical trials during the COVID-19 pandemic. It aims to “minimise disruption and preserve integrity”, while still ensuring participant health and safety.
Authors Mary M McDermott (deputy editor of JAMA, and Northwestern University, Chicago, USA) and Anne B Newman (University of Pittsburgh Graduate School of Public Health, Pittsburgh, USA) advise “creativity and persistence”. They point out: “Mitigation efforts interfere with all aspects of a successful clinical trial: efficient accrual and randomisation, intervention adherence and delivery, and outcome collection. Those most susceptible to severe consequences of coronavirus, older individuals and those with chronic disease, are commonly included in randomised trials designed to improve health in these vulnerable populations.”
They concede that, although one approach is to discontinue randomised trials that do not provide an immediate clear benefit to enrolled participants, the benefits are unknown until the trial is completed, and discontinuing ongoing trials wastes previously invested resources, as well as the time and effort of those who have already completed the trial.
“In contrast, sustaining ongoing trials could help millions of people realise substantial, durable health benefits that will be important once the coronavirus pandemic ends. Therefore, efforts and resources should be dedicated to support continuing randomised trials using creative and thoughtful methods and proactive planning. Adapting protocols to facilitate continued intervention adherence, outcome measurement, and some aspects of recruitment for trials already underway is likely to have the greatest benefit for the most people.”
Among the modifications they recommend are changes to how outcomes data are collected, and how interventions are delivered and monitored.
McDermott and Newman suggest prioritising outcomes, with the primary outcome given highest priority: “Outcomes that are exploratory or not prespecified are more appropriate to eliminate temporarily. Alternative methods for measuring primary outcomes that cannot be collected in-person should be prepared and protocols modified to facilitate collection of alternative self-reported or medical record data that can be adjudicated as a surrogate for the primary outcome.”
Those that can be collected remotely, such as self-administered outcomes or those collected by telephone or online, should be continued.
Safety and feasibility must be emphasised when considering the delivery of interventions, they say. Interventions that can be safely adhered to without leaving home should be continued, and it may be appropriate to continue some, such as medications, beyond the originally intended stop date. Others may need modification—for example, those that require participants to attend behavioural interventions requiring group visits or exercise sessions at a gym could be temporarily converted to a home-based session with remote monitoring.
The authors also urge consideration of how an intervention might interact with coronavirus infection, and whether a study drug should be continued if a participant becomes ill with symptoms of coronavirus. “Conceivably,” they point out, “some interventions could improve outcomes. For example, a trial testing efficacy of a therapy such as a statin might mitigate the cardiovascular consequences of an acute inflammatory state. If continuing the intervention becomes untenable, intention-to-treat methods are essential for understanding risks and protective factors for infection, illness, or recovery.”
However, McDermott and Newman finish, investigators should consider scaling back or placing selected studies on hold, if doing so does not substantially harm the trials, allowing research personnel to switch to work on urgent trials of interventions to address the coronavirus pandemic.