Platform trials during the COVID-19 pandemic – Challenges in identification and maintenance in the Cochrane COVID-19 Study Register (CCSR)
2CADTH Canadian Agency for Drugs and Technologies in Health (present affiliation); Cochrane Central Executive Team (sponsor), Canada
3Institute of General Practice, Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
4Cochrane Publishing & Technology Directorate, Cochrane, London, UK
During the COVID-19 pandemic, platform trials (PTs) such as RECOVERY and REMAP-CAP played an essential role in the rapid identification of effective treatments. These trials allowed trial arms to be added for new interventions during the course of the study, as the context of the pandemic changed. Clinical trials registers are an important source of information for the identification of studies on new drugs (Knelangen 2018). However, the initial registry entry of PTs does not list all interventions added during later stages.
Objectives: Within the scope of multiple COVID-19 Cochrane reviews, we aimed to identify and track potentially relevant PTs. Here, we focus on the methods and particular challenges.
Methods: In November 2020, we began a monthly search with a peer-reviewed search strategy for PTs in the Cochrane COVID-19 Study Register (CCSR). Two authors independently screened the results. In the CCSR, the identified PT records were maintained and tagged with the study type “Adaptive/Platform.” They were systematically monitored for information on added or dropped intervention arms, interim results, and trial status via their dedicated websites, twitter, or email alert or in the clinical trials registries. Information on available arms or missed trial study acronyms that were not presented in the initial trials register entries were added to the study record in the CCSR.
Results: Owing to the changing design of these trials, the search strategy required several revisions. The lack of study descriptors required us to conduct additional searches with study acronyms in ClinicalTrials.gov and the International Clinical Trials Registry Platform to identify multiple records. Furthermore, some trials have registry entries in more than one trials register. The number of PTs increased from inception to almost 75 (February 2023). Press releases emerged as an important source for updates on the results of the trials.
Conclusions: PTs became an important source to conduct, plan, and update multiple COVID-19 Cochrane reviews, including future Long-COVID reviews. Because of their continuous adaptation, PTs come with new challenges related to incomplete trials register records and identification of their results.
Patient, public and/or healthcare consumer involvement: In the CCSR, authors can easily identify PTs and newly linked references because of its study-based nature.