TY - JOUR
T1 - Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances
T2 - The CONSERVE 2021 Statement
AU - CONSERVE Group
AU - Orkin, Aaron M
AU - Gill, Peter J
AU - Ghersi, Davina
AU - Campbell, Lisa
AU - Sugarman, Jeremy
AU - Emsley, Richard
AU - Steg, Philippe Gabriel
AU - Weijer, Charles
AU - Simes, John
AU - Rombey, Tanja
AU - Williams, Hywel C
AU - Wittes, Janet
AU - Moher, David
AU - Richards, Dawn P
AU - Kasamon, Yvette
AU - Getz, Kenneth
AU - Hopewell, Sally
AU - Dickersin, Kay
AU - Wu, Taixiang
AU - Ayala, Ana Patricia
AU - Schulz, Kenneth F
AU - Calleja, Sabine
AU - Boutron, Isabelle
AU - Ross, Joseph S
AU - Golub, Robert M
AU - Khan, Karim M
AU - Mulrow, Cindy
AU - Siegfried, Nandi
AU - Heber, Joerg
AU - Lee, Naomi
AU - Kearney, Pamela Reed
AU - Wanyenze, Rhoda K
AU - Hróbjartsson, Asbjørn
AU - Williams, Rebecca
AU - Bhandari, Nita
AU - Jüni, Peter
AU - Chan, An-Wen
N1 - Funding Information:
grants from the Physicians’ Services Incorporated Foundation, the Canadian Institutes of Health Research (CIHR), and the Hospital for Sick Children and expenses to attend conferences and meetings reimbursed by the EBMLive Steering Committee and the CIHR Institute of Human Development, Child and Youth Health Institute Advisory Board. Dr Sugarman reported receipt of personal fees from Merck, IQVIA, Aspen Neurosciences, Biogen, and Portola Pharmaceuticals; in addition, he receives stock options not yet exercised from Aspen Neurosciences and nonfinancial support from Merck KGaA and IQVIA. Dr Steg reported receipt of grants and personal fees from Amarin, Bayer, Servier and Sanofi/Regeneron; personal fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Idorsia, Novartis, Novo Nordisk, Pfizer, Sanofi/Lexicon, and Myokardia; and personal fees and nonfinancial support from AstraZeneca. In addition, Dr Steg has a patent issued to Sanofi. Dr Weijer reported receipt of consulting income from Cardialen, Eli Lilly & Co, and RTI International. Dr Simes reported receipt of grants from the National Health and Medical Research Council of Australia, the Cancer Institute of New South Wales, Australia, Cancer Australia, Bayer, Roche, Pfizer, AstraZeneca, and Bristol Myers Squibb. Dr Wittes reported involvement in many studies that have been affected by COVID-19; the company for which she works, WCG Statistics Collaborative, has received consulting fees for those consultations. Dr Richards reported receipt of personal fees from Merck, Eli Lilly & Co, Novo Nordisk, and Innomar; consulting fees from Janssen and the CIHR Institute of Musculoskeletal Health and Arthritis; and being volunteer vice president of the Canadian Arthritis Patient Alliance, for which her efforts are supported via independent grants by pharmaceutical firms. Dr Ross reported receipt of grants from Johnson & Johnson, the FDA, the Agency for Healthcare Research and Quality, the Laura and John Arnold Foundation, the National Institutes of Health/ National Heart, Lung, and Blood Institute, and the Medical Devices Innovation Consortium and being a current US research and outreach editor at The BMJ. Dr Khan reported being scientific director of the CIHR Institute of Musculoskeletal Health and Arthritis. Dr Jüni reported serving as unpaid member of the steering group of trials funded by Appili Therapeutics, Astra Zeneca, Biotronik, Biosensors, St Jude Medical, and The Medicines Company; receiving research grants to his institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly & Co, and The Medicines Company; and receiving honoraria to his institution for participation in advisory boards and/or consulting from Amgen, Ava, and Fresenius; he has not received personal payments from any pharmaceutical company or device manufacturer. No other disclosures were reported.
Funding Information:
from the University of Toronto Department of Family and Community Medicine and the CIHR Postdoctoral Fellowship Program. Dr Emsley is supported by grant NIHR300051 from the National Institute of Health Research. Dr R. Williams’ work was supported by the Intramural Research Program of the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/20
Y1 - 2021/7/20
N2 - Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete.Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances.Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders.Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses.Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.
AB - Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete.Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances.Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders.Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses.Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.
UR - http://www.scopus.com/inward/record.url?scp=85108547061&partnerID=8YFLogxK
U2 - 10.1001/jama.2021.9941
DO - 10.1001/jama.2021.9941
M3 - Review article
C2 - 34152382
SN - 0098-7484
VL - 326
SP - 257
EP - 265
JO - JAMA
JF - JAMA
IS - 3
ER -