Abstract
Global health pandemics, such as coronavirus disease 2019 (COVID-19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent in-vitro and in-silico work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment. In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs. Well conducted, adaptive platform trials utilising a multi-arm multi-stage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial. The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for each further wave of COVID-19, and enable preparedness for future global health pandemics.
Highlights
Global health pandemics, such as coronavirus disease 2019 (COVID19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations
In response to the positive and helpful comments from both reviewers - further detail has been provided on international collaborative efforts supporting adaptive platform trials using multi-arm multistage (MAMS) protocols, as well as greater detail on discussion of points relating to design, conduct, analysis and reporting of MAMS platform trials in a pandemic setting
There is an urgent need for reliable evidence in pandemic settings, as illustrated by the COVID-19 pandemic
Summary
Any reports and responses or comments on the article can be found at the end of the article. In the context of a fast-moving infectious disease pandemic, it is likely that usual or standard care will change based on interim analysis of comparison arms (and reporting) from the current trial, or from emerging data and findings of other research studies. A key challenge to overcome for greater delivery and use of this design is to ensure collaboration between individuals and organisations with experience in delivering such trials In this respect, there are recent commendable international collaborative efforts to combine expertise and experience from across academia and industry, including the European union patient-centric clinical trial platforms (EU-PEARL) consortium and the clinical trials transformation initiative (CTTI). The WHO is commendably supporting global efforts for evaluation of multiple vaccines in a SOLIDARITY vaccine trial protocol[45]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
