The SPIRIT checklist specifies what a clinical trial protocol should contain, and the current version is SPIRIT 2025, which carries 34 items. Its name stands for Standard Protocol Items: Recommendations for Interventional Trials. It replaces SPIRIT 2013 and was developed alongside the CONSORT 2025 update, which is why the two now align item for item in most places.
A protocol is the only document in a trial's life that is written before anybody knows the answer, and that is exactly where its value sits. Every methodological protection a trial claims later, that the primary outcome was not chosen after seeing the data, that the analysis was not adjusted until it worked, that the subgroup finding was planned, rests on a dated document that said so in advance. SPIRIT is the list of things that document has to pin down.
What the protocol is protecting you from
It helps to be concrete about the failure the guideline prevents. A trial with three plausible outcome measures and no prespecified primary has, in effect, three chances to find an effect, and a reader has no way to know how many were looked at. A trial whose analysis adjusts for covariates chosen after unblinding has fitted the model to its own results. Neither of these requires bad faith; both happen through ordinary drift when nothing was written down.
Once results exist, no amount of careful writing can restore the distinction between confirmatory and exploratory. That is why the three hardest SPIRIT items are the three that cannot be repaired retrospectively: the primary outcome definition, the sample size justification, and the statistical analysis plan.
The 34 items by section
The items follow the structure of a protocol document. Described in our own words, they cover the following. The authoritative wording and official templates sit with the CONSORT and SPIRIT group and should be taken from there.
Administrative information. The title identifying the design and population, the trial registration number and registry with the data set, the protocol version and date, sources of funding, the roles and responsibilities of authors, sponsor and any committees, and the sponsor's role in design, analysis and the decision to publish.
Introduction. The background and rationale including a summary of relevant studies and the justification for the comparator, the specific objectives or hypotheses, and the trial design including allocation ratio and the framework, whether superiority, non-inferiority, equivalence or exploratory.
Methods, participants and interventions. The study setting and list of sites, eligibility criteria including criteria for sites and the individuals delivering the interventions, the interventions described in replicable detail, the circumstances under which they may be modified or discontinued, strategies for improving adherence and how it will be assessed, and any concomitant care permitted or prohibited.
Methods, outcomes and timeline. Completely defined primary and secondary outcomes including the measurement variable, the analysis metric, the aggregation method and the timing, with an explanation of clinical relevance; the participant timeline of enrolment, interventions and assessments; the sample size with all the assumptions behind it; and the recruitment strategy for reaching target numbers.
Methods, assignment. How the allocation sequence is generated including any stratification or blocking, the allocation concealment mechanism, who implements assignment, and who is blinded plus the circumstances under which unblinding is permitted.
Methods, data collection and management. The plans for assessing and collecting outcome and other data, plans to promote retention and complete follow-up including how data from participants who discontinue will be handled, data management including entry, coding and range checks, and confidentiality arrangements. Any plans for biological specimens are covered here too.
Methods, statistics and monitoring. The statistical methods for primary and secondary outcomes, methods for any additional analyses including subgroup and adjusted analyses, the definition of the analysis population and how missing data will be handled, the composition and role of any data monitoring committee, plans for interim analyses and stopping rules, plans for collecting and reporting harms, and the frequency and procedures for auditing.
Ethics and dissemination. Plans for seeking ethics approval, communicating protocol amendments, obtaining informed consent including for ancillary studies, declarations of interest, who has access to the final data set, provisions for ancillary and post-trial care, plans for dissemination to participants and the public including authorship and any reproducible research arrangements, and model consent materials.