Aug 22, 2020 Volume 396 Number 10250 p513-582
COVID-19 and readjusting clinical trials
Aaron van Dorn
The COVID-19 pandemic has disrupted clinical trials worldwide, with long-lasting effects on medical science. Aaron van Dorn reports.
The COVID-19 pandemic has created massive disruptions to clinical trial research across the world. As in other aspects of life, the virus has severely affected the ability to conduct trials in safe and effective ways. This is especially true when considering that trials often deal with vulnerable populations who are most at risk from exposure to COVID-19. Thousands of trials have been suspended or stopped because of the difficulties in continuing under lockdown conditions, even as those restrictions have begun to ease in parts of the world. At the same time, the pandemic has seen an unprecedented reorientation in clinical trials research towards COVID-19. Both of those aspects—the disruption and the fast, effective readjustment to address a new challenge—ensure that the effects of the COVID-19 pandemic will be felt in clinical trials research long after the initial effects have faded.
Clinical trials have long been a premier method of testing and validating new drugs and therapies. New drug approval is predicated on successful trials into the safety and efficacy of new treatments. Trials can involve hundreds of different sites around the world, all with different conditions and facing different effects and government regulations on what is permissible. Once you start looking at the number of people involved in a clinical trial, the scope of the problem begins to seem daunting. In addition to researchers who formulate the protocol for the trial and work to secure funding (either from governments, foundations, pharmaceutical or device manufacturers, or a combination of the above), clinical trials include clinical caregivers and nurses who work with patients at clinical trial sites, postgraduate researchers, postdoctoral fellows, research scientists, and others who work on the analysis of data generated by the trial, some of whom may or may not interact with patients, but all of whom are essential to the final result.
Trials that were stopped, in many cases, were stopped from enrolling new patients. Patients who were already enrolled mostly continued to receive treatment as institutions and researchers worked to make changes to how care was provisioned to deal with the reality of COVID-19. Fergus Sweeney, head of clinical studies and manufacturing at the European Medicines Agency, told The Lancet that one of the key parts of their guidance has been physical distancing to protect patients and clinic staff, but ensuring the safety of patients in testing and treatment is also important. “If people can’t come in to a clinic or their hospital at the usual, regular intervals, it may be that they need to be provided with a medication for a longer period of time, or indeed that medication is distributed to their home by a distributor”, Sweeney said. To that end, many trials have shifted from the distribution of drugs at the trial site to direct-to-patient courier services, whereby trial drugs are distributed and administered to patients in their homes, eliminating the need for at-risk patients to visit trial sites. Many in-person visits for checkups and other aspects of trials were shifted to teleconferencing services. In March, 2020 (and revised again in July), the US Food and Drug Administration (FDA) also issued guidance on protecting patient safety during the COVID-19 pandemic. The FDA guidelines called on researchers and trial sponsors to “determine that the protection of a participant’s safety, welfare, and rights is best served by continuing a study participant in the trial as per the protocol or by discontinuing the administration or use of the investigational product or even participation in the trial”. The guidance also calls on investigators and sponsors to coordinate with institutional review boards and ethics committees on potential changes to protocol as early as possible. But for many patients who have turned to clinical trials as a last resort for cardiovascular conditions, who have cancer, or other life-threatening conditions, the eventual resumption of non-COVID-19 trials could come too late.