Clinical Trials Impacted by the COVID-19 Pandemic: Adaptive Designs to the Rescue?. (1st October 2020)

• Record Type: Journal Article
• Authors: Kunz, Cornelia Ursula; Jörgens, Silke; Bretz, Frank; Stallard, Nigel; Van Lancker, Kelly; Xi, Dong; Zohar, Sarah; Gerlinger, Christoph; Friede, Tim
• Is Part Of: Statistics in biopharmaceutical research. Volume 12:Number 4(2020)
• Page Start: 461
• Page End: 477
• Publication Date: 2020-10-01
• Subjects: Design changes -- Heterogeneity -- Interim analysis -- SARS-CoV-2; Pharmacy -- Statistical methods -- Periodicals; Pharmaceutical biotechnology -- Statistical methods -- Periodicals; Biopharmaceutics -- Periodicals; Biometry -- Periodicals; Pharmacy -- Statistical methods; Periodicals; 615.190727
• DOI: 10.1080/19466315.2020.1799857
• Languages: English
• ISSNs: 1946-6315

Abstract

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 ongoing clinical trials in non-COVID-19 conditions. Motivated by four current 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 use early read-outs; and (v) how to use 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.