Guidelines for reporting trial protocols and completed trials modified due to the COVID-19 Pandemic and other extenuating circumstances: The CONSERVE 2021 Statement

Rigorous design and transparent reporting of randomized trials and trial protocols are key enablers of open science. Trials can face unavoidable modifications due to new safety or efficacy information, regulatory revisions, changes in the standard of care, and more. Modifications can prompt methodological, ethical, feasibility, and analytical challenges that threaten open science. The COVID pandemic disrupted thousands of trials involving millions of participants. Scientists had no guidance on how to interpret and report those disruptions. CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve the reporting of trials and trial protocols that undergo important modifications in response to extenuating circumstances. CONSERVE was developed using open science principles, led by a global panel of 37 trial investigators, methodologists, patient representatives, ethicists, funders, regulators, and journal editors. Our protocol was published on the Open Science Framework, involving a literature review, consensus-based panelist meetings using a modified Delphi process, and a global survey of trial stakeholders. The literature review yielded 38 relevant documents, but no generalizable guidance for reporting unanticipated modifications to trials and protocols. The panel used these findings to develop a consensus guideline. The global survey drew 198 respondents in 34 countries, of whom 90% understood the concept definitions and 85.4% could use the implementation tool. Feedback from survey respondents was used to finalize the guideline. CONSERVE was immediately publicly available in June 2021 through JAMA and the EQUATOR Network. CONSERVE offers tools and checklists to support transparent and rigorous reporting when trials and trial protocols face important modifications to the intended study. The panel is investigating the impacts of the CONSERVE 2021 Statement and the quality of trial reporting during the COVID pandemic.