gms | German Medical Science

23. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin e. V.

Deutsches Netzwerk Evidenzbasierte Medizin e. V.

01. - 03.09.2022, Lübeck

Development and uptake of the ‘CONSORT and SPIRIT Extension for RCTs reVised in Extenuating circumstances’ (CONSERVE) statement 2021 for the reporting of trial protocols and completed trials modified due to the COVID-19 pandemic and other extenuating circumstances

Meeting Abstract

  • Aaron Orkin - University of Toronto, Division of Emergency Medicine, Department of Family and Community Medicine, Toronto, Kanada; Dalla Lana School of Public Health, University of Toronto, Kanada
  • Peter Gill - University of Toronto, Hospital for Sick Children, Department of Paediatrics, Toronto, Kanada
  • Davina Gehrsi - National Health and Medical Research Council, Australien
  • Lisa Campbell - Clinical Trials Unit, Medicines and Healthcare Products Regulatory Agency, Großbritannien
  • Jeremy Sugarman - Johns Hopkins University, Berman Institute of Bioethics, USA
  • Richard Emsley - King's College London, Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology, and Neuroscience, London, Großbritannien
  • Philippe Gabriel Steg - Université de Paris, AP-HP, Paris, Frankreich
  • Charles Weijer - Western University, Departments of Medicine, Epidemiology and Biostatistics, and Philosophy, Kanada
  • John Simes - University of Sydney, National Health and Medical Research Council Clinical Trials Centre, Sydney, Australien
  • Tanja Rombey - Technische Universität Berlin, Department of Health Care Management, Berlin, Germany
  • Hywel Williams - University of Nottingham, Nottingham, Großbritannien; National Institute for Health Research, Großbritannien
  • Janet Wittes - WCG Statistics Collaborative, USA
  • David Moher - University of Ottawa, Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, School of Epidemiology and Public Health, Ottawa, Kanada
  • Dawn Richards - Clinical Trials Ontario, Kanada
  • Yvette Kasamon - Office of Oncologic Diseases, Center for Drug Evaluation and Research, US Food and Drug Administration, USA
  • Kenneth Getz - Tufts Center for the Study of Drug Development, USA
  • Sally Hopewell - University of Oxford, Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Oxford, Großbritannien
  • Kay Dickersin - Johns Hopkins Bloomberg School of Public Health, USA
  • Taixiang Wu - Sichuan University, Chinese Clinical Trial Registry, China
  • Ana Patricia Ayla - University of Toronto, Gerstein Science Information Centre, Toronto, Kanada
  • Kenneth Schulz - FHI 360, USA; University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, USA
  • Sabine Calleja - University of Toronto, Gerstein Science Information Centre, Toronto, Kanada
  • Isabelle Boutron - Université de Paris, Centre of Research in Epidemiology and Statistics, Paris, Frankreich
  • Joseph Ross - Yale School of Medicine, Department of Internal Medicine, USA; The BMJ, Großbritannien
  • Robert Golub - Deputy Editor JAMA, USA; Northwestern University Feinberg School of Medicine, Department of Medicine, USA
  • Karim Khan - Canadian Institutes of Health Research Institute of Musculoskeletal Health and Arthritis, Kanada
  • Cindy Mulrow - University of Texas, Health Science Center, USA
  • Nandi Siegfried - South African Medical Research Council, Alcohol, Tobacco, and Other Drugs Research Unit, Südafrika
  • Joerg Heber - Lawrence Berkeley National Laboratory, Berkeley, USA
  • Naomi Lee - The Lancet, Großbritannien
  • Pamela Reed Kearney - National Institutes of Health, Office of Extramural Research, Division of Human Subjects Research, USA
  • Rhoda Wanyenze - Makerere University, Department of Disease Control and Environmental Health, School of Public Health, Uganda
  • Asbjørn Hróbjartsson - University of Southern Denmark, Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, Dänemark
  • Rebecca Williams -, National Library of Medicine, National Institutes of Health, USA
  • Nita Bhandari - Society for Applied Studies, Centre for Health Research and Development, Indien
  • Peter Jüni - University of Toronto, Applied Health Research Centre, St Michael's Hospital, Toronto, Kanada
  • An-Wen Chan - University of Toronto, Women's College Research Institute, Department of Medicine, Toronto, Kanada

Evidenzbasierte Medizin für eine bedarfsgerechte Gesundheitsversorgung. 23. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin. Lübeck, 01.-03.09.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. Doc22ebmVS-9-04

doi: 10.3205/22ebm055, urn:nbn:de:0183-22ebm0557

Published: August 30, 2022

© 2022 Orkin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



Background/research question: Randomized controlled trials (RCTs) are the gold standard for assessing the effectiveness of interventions. Their conduct is strictly regulated to maintain ethical and research integrity. Nevertheless, extenuating circumstances, such as the COVID-19 pandemic or war, may result in unavoidable modifications to RCTs. Such modifications pose methodological, ethical, feasibility, and analytical challenges, and it is crucial they are transparently reported. Therefore, we developed a joint extension for the CONSORT and SPIRIT reporting guidelines for RCTs and RCT protocols: the CONSERVE 2021 statement [1].

Methods: CONSERVE was developed between June 2020 and February 2021 by an international panel of 37 researchers, patient representatives, ethicists, funders, regulators, and journal editors (the CONSERVE Group) following an a priori protocol [2]. An accelerated process consisting of three partially overlapping steps was applied: First, we performed a rapid review in MEDLINE, Embase, CINAHL, and gray literature sources from 2003 to March 2021. Second, using a modified Delphi process, we held virtual consensus-based panelist meetings followed by surveys sent out to the members. Last, we sent out a global survey to trial stakeholders from the wider network of the group. CONSERVE was published in July 2021 and its uptake (based on citing references) within the first year is currently being assessed.

Results: The rapid review retrieved 41,673 unique citations, of which 38 were deemed relevant and informed the panelist meetings and surveys. Consensus, defined as a stage when no panelist called for further revisions, was achieved following three panelist meetings. The global survey received responses from 198 individuals from 34 countries. A fourth consensus meeting was held to include results from the rapid review and global survey. The final CONSERVE statement consists of an implementation tool and two checklists (one for RCT protocols and one for completed RCTs), consisting of four sections each: extenuating circumstances, important modifications (including their impact and mitigating strategies), responsible parties, and interim data analyses.

Conclusion: CONSERVE aims to improve the transparency, quality, and completeness of reporting important modifications to RCTs and RCT protocols due to extenuating circumstances, such as the COVID-19 pandemic. To realize this aim, it is crucial that CONSERVE is widely disseminated and endorsed to increase its uptake by trial authors.

Competing interests: Dr Gill reported 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.


Orkin AM, Gill PJ, Ghersi D, Campbell L, Sugarman J, Emsley R, Steg PG, Weijer C, Simes J, Rombey T, Williams HC, Wittes J, Moher D, Richards DP, Kasamon Y, Getz K, Hopewell S, Dickersin K, Wu T, Ayala AP, Schulz KF, Calleja S, Boutron I, Ross JS, Golub RM, Khan KM, Mulrow C, Siegfried N, Heber J, Lee N, Kearney PR, Wanyenze RK, Hróbjartsson A, Williams R, Bhandari N, Jüni P, Chan AW; CONSERVE Group. Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement. JAMA. 2021 Jul 20;326(3):257-65. DOI: 10.1001/jama.2021.9941 External link
Orkin AM, Gill PJ, Jüni P, Ghersi A, Chan A-W. Development Protocol – CONSORT and SPIRIT Extension for RCTs reVised in Extenuating Circumstances. OSF. 2021. DOI: 10.17605/OSF.IO/MS8BZ External link