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This JAMA Guide to Statistics and Methods discusses the CONSERVE guidelines, which address how to report extenuating circumstances that lead to a modification in trial design, conduct, or analysis.
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In the COVID-19 Dexamethasone (CoDEX) randomized clinical trial, which studied a sample of critically ill patients with COVID-19, the use of dexamethasone significantly increased the number of ventilator-free days and was not associated with an increased risk of adverse events.1 During the course of the study, data from the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial became available and demonstrated benefit with dexamethasone in a comparable patient population.2 Members of the CoDEX independent data and safety monitoring committee (DSMC) recommended stopping the CoDEX trial because they did not consider it ethical to continue the trial as originally designed.
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The unplanned termination of CoDEX shows how studies can be stopped as new external information becomes available. This information may be based on reporting of results from a different study, as occurred with CoDEX, or may be due to other extenuating circumstances outside the control of the study. With the early termination of the study, the CoDEX investigators encountered the challenge of conveying a significant amount of information about the conduct of the study as well as the evidence and rationale for the early termination. The CONSERVE guidelines serve as a guide to researchers to support thorough reporting in challenging circumstances.3
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WHAT ARE THE CONSERVE GUIDELINES?
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The CONSORT4 and SPIRIT5 guidelines have been widely used to standardize the process for reporting clinical trial results and trial designs, respectively. The CONSERVE guidelines extend the CONSORT and SPIRIT guidelines by addressing how to report extenuating circumstances that lead to a modification in trial design, conduct, or analysis.3 Many articles have focused on the methods for appropriately conducting and reporting interim analyses of trial data.6,7 In contrast, clear guidance has been lacking for reporting the circumstances and actions when modifications in a clinical trial are based on external events. The CONSERVE guidelines offer a structured process for using study data that have already been collected when conditions change, and they provide a mechanism for reporting the ensuing changes with rigor and transparency.
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The CONSERVE reporting guidelines3 are intended for trials that have undergone important modifications because of unexpected circumstances that are outside of the investigators’ control. Examples of external circumstances extend beyond COVID-19 and include natural disasters8 or pandemics that interrupt trials temporarily or stop them permanently, new knowledge about the safety profile of a drug or device, changes in standard care such that patients who were once eligible for a trial are no longer eligible, sponsor financial decisions, and availability of required resources.9 Important modifications are meaningful changes to the trial design or implementation. These modifications can involve the trial aims, available treatment groups, the risks and benefits to ...