CONSORT extension for the reporting of randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE): checklist with explanation and elaboration

Randomised controlled trials are increasingly conducted as embedded, nested, or using cohorts or routinely collected data, including registries, electronic health records, and administrative databases, to assess if participants are eligible for the trial and to facilitate recruitment, to deliver an embedded intervention, to collect trial outcome data, or a combination of these purposes. This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE). The extension was developed to look at the unique characteristics of trials conducted with these types of data with the goal of improving reporting quality in the long term by setting standards early in the process of uptake of these trial designs. The extension was developed with a sequential approach, including a Delphi survey, a consensus meeting, and piloting of the checklist. The checklist was informed by the CONSORT 2010 statement and two reporting guidelines for observational studies, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the REporting of studies Conducted using Observational Routinely collected Data (RECORD) statement. The extension includes eight items modified from the CONSORT 2010 statement and five new items. Reporting items with explanations and examples are provided, including key aspects of trials conducted using cohorts or routinely collected data that require specific reporting considerations.


Introduction
Background and objectives 2a Scientific background and explanation of rationale 2b Specific objectives or hypotheses

Methods
Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio, that a cohort or routinely collected database(s) was used to conduct the trial (such as electronic health record, registry) and how the data were used within the trial (such as identification of eligible trial participants, trial outcomes) 3b Important changes to methods after trial commencement (such as eligibility criteria), with reasons Cohort or routinely collected database

ROUTINE-1
Name, if applicable, and description of the cohort or routinely collected database(s) used to conduct the trial, including information on the setting (such as primary care), locations, and dates, (such as periods of recruitment, follow-up, and data collection) ROUTINE-2 Eligibility criteria for participants in the cohort or routinely collected database(s)

ROUTINE-3
State whether the study included person-level, institutional-level, or other data linkage across two or more databases and, if so, linkage techniques and methods used to evaluate completeness and accuracy of linkage Trial participants 4a Eligibility criteria for trial participants, including information on how to access the list of codes and algorithms used to identify eligible participants, information on accuracy and completeness of data used to ascertain eligibility, and methods used to validate accuracy and completeness (e.g., monitoring, adjudication), if applicable 4b Settings and locations where the data were collected ROUTINE-4 Describe whether and how consent was obtained The interventions for each group with sufficient details to allow replication, including how and when they were actually administered Outcomes 6a Completely defined pre-specified primary and secondary outcome measures, including how and when they were ascertained and the cohort or routinely collected database(s) used to ascertain each outcome

ROUTINE-5
Information on how to access the list of codes and algorithms used to define or derive the outcomes from the cohort or routinely collected database(s) used to conduct the trial, information on accuracy and completeness of outcome variables, and methods used to validate accuracy and completeness (e.g., monitoring, adjudication), if applicable 6b Any changes to trial outcomes after the trial commenced, with reasons Sample size 7a How sample size was determined 7b When applicable, explanation of any interim analyses and stopping guidelines Randomisation: Sequence generation 8a Method used to generate the random allocation sequence 8b Type of randomisation; details of any restriction (such as blocking and block size) Allocation concealment mechanism 9 Mechanism used to implement the random allocation sequence (such as embedding an automated randomiser within the cohort or routinely collected database(s)), describing any steps taken to conceal the sequence until interventions were assigned Implementation 10 Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how 11b If relevant, description of the similarity of interventions Statistical methods 12a Statistical methods used to compare groups for primary and secondary outcomes 12b

Results
Participant flow (a diagram is strongly recommended) 13a For each group, the number of participants in the cohort or routinely collected database(s) used to conduct the trial and the numbers screened for eligibility, randomly assigned, offered and accepted interventions (e.g., cohort multiple RCTs), received intended treatment, and analysed for the primary outcome 13b For each group, losses and exclusions after randomisation, together with reasons For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) 17b For binary outcomes, presentation of both absolute and relative effect sizes is recommended

Ancillary analyses 18
Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory

Harms 19
All important harms or unintended effects in each group (for specific guidance see CONSORT for harms)

Discussion
Limitations 20 Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses Generalisability 21 Generalisability (external validity, applicability) of the trial findings Interpretation 22 Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence, including the implications of using data that were not collected to answer the trial research questions