SPIRIT 2025 Updated the Reporting Guideline for Randomised Trial Protocols

SPIRIT, which stands for Standard Protocol Items: Recommendations for Interventional Trials, is a reporting guideline that sets out the minimum content a clinical trial protocol should include. The original SPIRIT statement was published in 2013. The updated SPIRIT 2025 statement focuses specifically on protocols of randomised trials and was published on 28 April 2025.

The statement was published simultaneously in several journals. The BMJ version carries the publication date of 28 April 2025, PLOS Medicine lists the same date, and JAMA published the statement online and later in its issue of 5 August 2025, where PubMed classifies it as a practice guideline. A version also appeared in Nature Medicine. This multi-journal approach is intended to make the guideline widely available to researchers, editors and reviewers.

The core output is an evidence-based checklist of 34 minimum items to address in a trial protocol, together with a diagram illustrating the schedule of enrolment, interventions and assessments.

The update followed a structured consensus process. According to the published statement, 317 people took part in a three-round Delphi survey, and 30 experts attended a subsequent consensus meeting. The group also integrated key items from other relevant reporting guidelines so that protocol authors do not need to consult several separate documents for common topics.

The process led to the addition of two new protocol items, revisions to five items and the deletion or merger of five items. Alongside the changes to individual items, the structure of the checklist was revised to include a new section on open science.

The published statement highlights four main changes. First, a new open science section groups together items relating to the transparency of the trial and its outputs. Second, the guideline gives additional emphasis to the assessment of harms. Third, it places more emphasis on the description of interventions and comparators. Fourth, it introduces a new item asking how patients and the public will be involved in the design, conduct and reporting of the trial.

The emphasis on harms and on interventions and comparators is relevant to ethics committees and regulators as well as to journals, since a protocol that specifies these elements clearly is easier to assess. The patient and public involvement item reflects wider expectations from funders and research organisations that trials should be informed by the people they are intended to benefit.

The full published statement and checklist should be consulted for the exact wording and numbering of each item, as summaries do not always reflect the final text. For organisations that maintain protocol templates, the practical effect of these changes is that sections previously scattered across a protocol, or omitted, now need a defined place, and that harms and comparator descriptions may need more detail than templates written for SPIRIT 2013 provide.

Protocol authors should update their templates to follow the SPIRIT 2025 checklist, including the new open science section and the patient and public involvement item. Sponsors with in-house protocol templates aligned with SPIRIT 2013 or with ICH guidance should map the new and revised items and decide where they will be addressed. Many journals that publish protocols and many funders refer to SPIRIT, so alignment with the 2025 version is likely to be expected for new submissions.

Medical writers can use the checklist as a quality control tool before a protocol is submitted to an ethics committee, regulator or journal. Completing the checklist, with page references, is a practical way to show reviewers that the protocol addresses the minimum content expected internationally. SPIRIT 2025 is a reporting guideline, not a regulatory requirement, and national rules on protocol content continue to apply.

Teams writing protocols for regulated medicinal product trials will also need to reconcile SPIRIT 2025 with regulatory expectations on protocol content, such as those in ICH guidance and national clinical trial legislation. In most cases the two are complementary: SPIRIT sets out what a protocol should report so that readers can understand and appraise the trial, while regulatory requirements govern what must be submitted for authorisation. Using a single template that satisfies both reduces duplication and the risk of inconsistency between versions submitted to different bodies.