Integrating pragmatism and rigor - impact of the pandemic on a randomized controlled trial of a complex intervention

The objectives here were to present a model of transparent reporting and pragmatic RCT design adaptation, and to promote discussion regarding best practices for overcoming the challenge of detecting intervention-specific changes in pain within the context of variable psychosocial factors due to the pandemic. Methods included an ongoing randomized, double-blind, placebo-controlled trial is examining the effect of pain education combined with exercise on pain in patients with chronic Achilles tendinopathy. We hypothesized that a biopsychosocial approach to patient education would reduce movement-evoked pain more than standard care (biomedical education and exercise). Since March 2020, challenges have included a temporary halt of in-person human subjects research, adapting virtual screening procedures to maintain confidentiality and safety, need to obtain telehealth license in multiple states, inability to use specialized laboratory equipment to evaluate secondary outcomes, and gradual resumption of in-person visits with PPE. As COVID-19 prevented the trial from proceeding as planned, we adapted our design to both exploit new opportunities and maintain high standards of transparency and rigor. We maintained study enrollment by modifying screening, evaluation, and treatment to accommodate virtual participation with consistent content. We adjusted our aims to include an a priori hypothesis that differential effects of a biopsychosocial versus biomedical approach on pain may be magnified during a pandemic. Additionally, strategies developed to adapt to an altered research-environment may be useful tools for future RCTs to facilitate participant recruitment and retention. We logged changes in a time-stamped manner on Open Science Framework; full disclosure will be ensured in final reports at Clinicaltrials.gov and publications. Adaptive designs are at risk of low confidence unless full transparency is integrated into research processes. Our own efforts to integrate changes to research design and conduct, with contemporary standards of transparency and rigor, provide opportunities for future research practice during and post-COVID. Funding for this study was provided by the National Institute of Arthritis Musculoskeletal and Skin Disease (NIAMS) research grant R00 AR071517 and by the Collaborative Research Grant from the International Association for the Study of Pain (IASP). Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002537. These funding sources had no role in study design, collection, analysis/interpretation of data, or decision on submission for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.