Clinical trials impacted by the COVID-19 pandemic: Adaptive designs to the rescue?

Cornelia Ursula Kunz; Silke Jörgens; Frank Bretz; Nigel Stallard; Kelly Van Lancker; Dong Xi; Sarah Zohar; Christoph Gerlinger; Tim Friede

arXiv · 2005.13979

Clinical trials impacted by the COVID-19 pandemic: Adaptive designs to the rescue?

Cornelia Ursula Kunz·Silke Jörgens·Frank Bretz·Nigel Stallard·Kelly Van Lancker·Dong Xi·Sarah Zohar·Christoph Gerlinger·Tim Friede

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Abstract

Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for the ongoing clinical trials in non-COVID-19 conditions. Motivated by four currently ongoing clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs. Guidance is provided on (i) where blinded adaptations can help; (ii) how to achieve type I error rate control, if required; (iii) how to deal with potential treatment effect heterogeneity; (iv) how to utilize early readouts; and (v) how to utilize Bayesian techniques. In more detail approaches to resizing a trial affected by the pandemic are developed including considerations to stop a trial early, the use of group-sequential designs or sample size adjustment. All methods considered are implemented in a freely available R shiny app. Furthermore, regulatory and operational issues including the role of data monitoring committees are discussed.

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Cornelia Ursula Kunz, Silke Jörgens, Frank Bretz, Nigel Stallard, Kelly Van Lancker, Dong Xi, Sarah Zohar, Christoph Gerlinger, Tim Friede. 2020-05-28. Clinical trials impacted by the COVID-19 pandemic: Adaptive designs to the rescue?. https://arxiv.org/abs/2005.13979

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