Table 2.

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist: recommended items are addressed in this clinical trial’s protocol and related documents.

Section or item, item no.			Description	Page no. where addressed
Administrative information
	Title
		1	Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym	1
	Trial registration
		2a	Trial identifier and registry name; if not yet registered, name of intended registry (ie, ClinicalTrials.gov, ID: NCT03366740)	2
		2b	All items from the World Health Organization Trial Registration Data Set	N/Aa
	Protocol version
		3	Date and version identifier	4
	Funding
		4	Sources and types of financial, material, and other support	20
	Roles and responsibilities
		5a	Names, affiliations, and roles of protocol contributors	1
		5b	Name and contact information for the trial sponsor (ie, the icddr,bb)	N/A
		5c	Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities	5
		5d	Composition, roles, and responsibilities of the coordinating center, steering committee, end-point adjudication committee, data-management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data-monitoring committee) (ie, Institutional Review Board and the icddr,b)	4, 5
Introduction
	Background and rationale
		6a	Description of research question and justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention	3, 4
		6b	Explanation for choice of comparators	3, 4
	Objectives
		7	Specific objectives or hypotheses	18
	Trial design
		8	Description of trial design, including type of trial (eg, parallel group, crossover, factorial, or single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, and exploratory)	13, 14
Methods: participants, interventions, and outcomes
	Study setting
		9	Description of study settings (eg, community clinic and academic hospital) and list of countries where data will be collected; reference to where list of study sites can be obtained	12
	Eligibility criteria
		10	Inclusion and exclusion criteria for participants; if applicable, eligibility criteria for study centers and individuals who will perform the interventions (eg, surgeons and psychotherapists)	13
	Interventions
		11a	Interventions for each group with sufficient detail to allow for replication, including how and when they will be administered	13, 14
		11b	Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, and improving or worsening disease)	17
		11c	Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return and laboratory tests)	N/A
		11d	Relevant concomitant care and interventions that are permitted or prohibited during the trial	17, 18
	Outcomes
		12	Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, and time to event), method of aggregation (eg, median and proportion), and time point for each outcome; explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended	18
	Participant timeline
		13	Time schedule of enrollment; interventions, including any run-ins and washouts; assessments; and visits for participants—a schematic diagram is highly recommended (see Table 1)	5, 6
	Sample size
		14	Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations	19
	Recruitment
		15	Strategies for achieving adequate participant enrollment to reach target sample size	N/A
Methods: assignment of interventions (for controlled trials)
	Allocation: sequence generation
		16a	Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification; to reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enroll participants or assign interventions (ie, block randomization)	18
	Allocation: concealment mechanism
		16b	Mechanism of implementing the allocation sequence (eg, central telephone and sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned	18
	Allocation: implementation
		16c	Study members who will generate the allocation sequence, will enroll participants, and will assign participants to interventions (ie, allocation sequence: senior scientist not related to the study; enrollment and assignment: principal investigator and study physician)	18
	Allocation: blinding (masking)
		17a	Study members who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, and data analysts), and how (ie, open-labeled trial)	18
		17b	If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s allocated intervention during the trial	N/A
Methods: data collection, management, and analysis
	Data collection methods
		18a	Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements and training of assessors) and a description of study instruments (eg, questionnaires and laboratory tests), along with their reliability and validity, if known; reference to where data collection forms can be found, if not in the protocol	15, 16
		18b	Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols	N/A
	Data management
		19	Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry and range checks for data values); reference to where details of data-management procedures can be found, if not in the protocol	19
	Statistical methods
		20a	Statistical methods for analyzing primary and secondary outcomes; reference to where other details of the statistical analysis plan can be found, if not in the protocol	19
		20b	Methods for any additional analyses (eg, subgroup and adjusted analyses)	19
		20c	Definition of analysis population relating to protocol nonadherence (eg, as randomized analysis), and any statistical methods to handle missing data (eg, multiple imputation)	N/A
Methods: monitoring
	Data monitoring
		21a	Composition of data-monitoring committee, summary of its role and reporting structure, statement of whether it is independent from the sponsor and competing interests, and reference to where further details about its charter can be found, if not in the protocol; alternatively, an explanation of why a data-monitoring committee is not needed	5
		21b	Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial—no interim analyses in this trial	N/A
	Harms
		22	Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct	5
	Auditing
		23	Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor	4
Ethics and dissemination
	Research ethics approval
		24	Plans for seeking research ethics committee (REC) and institutional review board (IRB) approval	4
	Protocol amendments
		25	Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, and analyses) to relevant parties (eg, investigators, RECs, IRBs, trial participants, trial registries, journals, and regulators)	5
	Consent or assent
		26a	Study members who will obtain informed consent or assent from potential trial participants or authorized surrogates, and how (see Item 32) (ie, principal investigator and his or her representative)	N/A
		26b	Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable	N/A
	Confidentiality
		27	How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial	4
	Declaration of interests
		28	Financial and other competing interests for principal investigators for the overall trial and each study site	20
	Access to data
		29	Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators	4
	Ancillary and posttrial care
		30	Provisions, if any, for ancillary and posttrial care and for compensation to those who suffer harm from trial participation	N/A
	Dissemination policy
		31a	Plans for investigators and sponsor to communicate trial results to participants, health care professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, and other data-sharing arrangements), including any publication restrictions	4
		31b	Authorship eligibility guidelines and any intended use of professional writers	N/A
		31c	Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code	N/A
Appendices
	Informed consent materials
		32	Model consent form and other related documentation given to participants and authorized surrogates (see Multimedia Appendix 1)	N/A
	Biological specimens
		33	Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable (see Table 1)	5, 6

^aN/A: not applicable.

^bicddr,b: International Centre for Diarrhoeal Disease Research, Bangladesh.