Table 2.

ACE checklist for the main report

Section/ Topic	Item No	Standard CONSORT 2010 checklist item	Extension for adaptive design randomised trials	Page No
Title and abstract	1a	Identification as a randomised trial in the title
	1b	Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) [136, 137]	Structured summary of trial design, methods, results, and conclusions (for specific guidance see ACE for abstracts, Table 3)
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
	3b«a		Type of adaptive design used, with details of the pre-planned trial adaptations and the statistical information informing the adaptations
	3c«3bb	Important changes to methods after trial commencement (such as eligibility criteria), with reasons	Important changes to the design or methods after trial commencement (such as eligibility criteria) outside the scope of the pre-planned adaptive design features, with reasons
Participants	4a	Eligibility criteria for participants
	4b	Settings and locations where the data were collected
Interventions	5	The interventions for each group with sufficient details to allow replication, including how and when they were actually administered
Outcomes	6ab	Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed	Completely define pre-specified primary and secondary outcome measures, including how and when they were assessed. Any other outcome measures used to inform pre-planned adaptations should be described with the rationale
	6bb	Any changes to trial outcomes after the trial commenced, with reasons	Any unplanned changes to trial outcomes after the trial commenced, with reasons
Sample size and operating characteristics	7ab	How sample size was determined	How sample size and operating characteristics were determined
	7bc	When applicable, explanation of any interim analyses and stopping guidelines	Pre-planned interim decision-making criteria to guide the trial adaptation process; whether decision-making criteria were binding or non-binding; pre-planned and actual timing and frequency of interim data looks to inform trial adaptations
Randomisation
Sequence generation	8a	Method used to generate the random allocation sequence
	8bb	Type of randomisation; details of any restriction (such as blocking and block size)	Type of randomisation; details of any restriction (such as blocking and block size); any changes to the allocation rule after trial adaptation decisions; any pre-planned allocation rule or algorithm to update randomisation with timing and frequency of updates
Allocation concealment mechanism	9	Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), 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
	11ca		Measures to safeguard the confidentiality of interim information and minimise potential operational bias during the trial
Statistical methods	12ab	Statistical methods used to compare groups for primary and secondary outcomes	Statistical methods used to compare groups for primary and secondary outcomes, and any other outcomes used to make pre-planned adaptations
	12b«a		For the implemented adaptive design features, statistical methods used to estimate treatment effects for key endpoints and to make inferences
	12c«12b	Methods for additional analyses, such as subgroup analyses and adjusted analyses
Results
Participant flow (a diagram is strongly recommended)	13ab	For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome	For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome and any other outcomes used to inform pre-planned adaptations, if applicable
	13b	For each group, losses and exclusions after randomisation, together with reasons
Recruitment and adaptations	14ab	Dates defining the periods of recruitment and follow-up	Dates defining the periods of recruitment and follow-up, for each group
	14bd	Why the trial ended or was stopped	See expanded E&E text for clarification
	14ca		Specify what trial adaptation decisions were made in light of the pre-planned decision-making criteria and observed accrued data
Baseline data	15a«15d	A table showing baseline demographic and clinical characteristics for each group	See expanded E&E text for clarification
	15ba		Summary of data to enable the assessment of similarity in the trial population between interim stages
Numbers analysed	16d	For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups	See expanded E&E text for clarification
Outcomes and estimation	17ad	For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval)	See expanded E&E text for clarification
	17b	For binary outcomes, presentation of both absolute and relative effect sizes is recommended
	17ca		Report interim results used to inform interim decision-making
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) [138]
Discussion
Limitations	20d	Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses	See expanded E&E text for clarification
Generalisability	21d	Generalisability (external validity, applicability) of the trial findings	See expanded E&E text for clarification
Interpretation	22	Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence
Other information
Registration	23	Registration number and name of trial registry
Protocol	24a«24	Where the full trial protocol can be accessed
SAP and other relevant trial documents	24ba		Where the full statistical analysis plan and other relevant trial documents can be accessed
Funding	25	Sources of funding and other support (such as supply of drugs), role of funders

“X« Y” means original CONSORT 2010 item Y has been renumbered to X;

“X«” means item reordering resulted in new item X replacing the number of the original CONSORT 2010″ item X”;

ACE Adaptive designs CONSORT Extension, E&E explanation and elaboration, SAP statistical analysis plan

^aNew items that should only be applied in reference to ACE;

^bModified items that require reference to both CONSORT 2010 and ACE;

^cReplacement (modified) item that only requires reference to ACE;

^dItem wording remains unchanged in reference to CONSORT 2010 but we expanded the ACE explanatory text to clarify additional considerations for certain adaptive designs. These unchanged items require reference to CONSORT 2010 except for item 14b