Commentary on Meyers et al: Ethically prioritizing trials in the COVID-19 era – practical considerations

Abstract

The devastation wrought by the SARS-CoV2 (COVID19) pandemic has created enormous urgency to conduct research on as many candidate tests, treatments and vaccines as possible as quickly as possible. As of 7 December 2020, there were 4,104 COVID-19 studies on ClinicalTrials.gov. Even as COVID-19 cases rise nationally, many studies preclude enrollment in other trials simultaneously and, at the local level, different trials can still end up competing for the same pool of patients. Moreover, research on COVID-19 can place demands on other institutional resources, such as laboratory and pharmacy capacity, limiting the ability to conduct research. The possibility of competing clinical trials has received some attention in the past. Patients with HIV infection, or with various cancers, can be eligible for multiple, mutually exclusive trials. Such competing studies raise practical and ethical challenges regarding how to allocate limited resources and whether patients must be informed of all trials for which they might qualify. But the plethora of COVID-19 trials and the push to carry them out quickly while adhering to social distancing and other requirements has raised the profile of these concerns and generated new challenges. Against this backdrop, Meyer et al. propose a novel three-tiered ethics framework for how health care institutions might prioritize COVID-19 clinical trials. In the first stage, a study is assessed for threshold criteria of social and scientific value, and similar studies are consolidated, if possible. At the second stage, institutions determine whether they can support all studies that pass the first stage based on availability of institutional resources; if not, prioritization and triage commence in a rather complex third stage. This third stage entails examining a number of ‘‘study specific criteria,’’ such as the relative likelihood and magnitude of each study’s potential benefits and its impact on resources, as well as ‘‘portfolio diversity criteria’’ that attempt to broaden COVID-19 research along various dimensions, including patients’ health statuses, disease stages, and socio-demographic diversity. What Meyer et al. propose is valuable, though institutional prioritization committees, like those at our institutions and many others around the country, will need additional guidance to apply this framework. Considerations of scientific merit, for instance, appear throughout the stages. In our experience, by the time studies reach the need for prioritization, their scientific merit may have already been assessed (i.e. having been reviewed by the Food and Drug Administration, National Institutes of Health, sponsors, and others), often by committees with greater expertise than an institutional prioritization committee. Moreover, prioritization decisions must be made quickly, and valuable time could be lost if these committees must again comprehensively review the science. While scientific merit is always part of the discussion, prioritization committees should rely on prior reviews so that they can focus squarely on prioritization itself. As a practical matter, we have found that the promise of an intervention or the robustness of scientific design are rarely sufficient to prioritize studies within an institution. The magnitude or likelihood of risks and benefits in a study is often uncertain, making it difficult to ascertain whether one study offers greater