Clinical Trial Protocol Template (SPIRIT 2025)

Randomised trial protocol following the 34 SPIRIT 2025 items: open science, PPI, interventions, harms, timeline, monitoring

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Anleitung: Use before enrolment to write the protocol submitted to ethics and the registry. Fill the outcomes, harms and sample size sections first because they drive the rest, then the open science and dissemination plans. The main pitfall is a data sharing plan that the consent form does not permit.

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Clinical Trial Protocol: [Full trial title]

Protocol template for a randomised clinical trial. The sections follow the topics and order of the SPIRIT 2025 Statement (administrative information, open science, introduction, methods, ethics), which replaced SPIRIT 2013 and has 34 checklist items plus a participant timeline figure. Topics are written in original words for this collection; use the template with the official SPIRIT 2025 checklist from consort-spirit.org and with your regulator's and sponsor's requirements (for example ICH E6 Good Clinical Practice). This is a document format, not clinical, regulatory or statistical advice. Replace every [bracketed] value and every row marked Example.

Document control

Field	Value
Document ID	[PROT-ACRONYM-001]
Trial acronym	[ACRONYM]
Protocol version	[1.0]
Version date	YYYY-MM-DD
Status	[Draft / In review / Approved / Superseded]
Owner	[@chief-investigator]
Approvers	[@sponsor-representative], [@trial-statistician]
Ethics reference	[REC / IRB reference]
Regulatory reference	[Clinical trial authorisation number or "not applicable"]
Reporting guideline	SPIRIT 2025 [plus extensions used]
Last updated	YYYY-MM-DD
Classification	[Confidential]

Approvals

Role	Name	Signature reference	Date
Chief investigator	[@name]	[Reference]	YYYY-MM-DD
Sponsor representative	[@name]	[Reference]	YYYY-MM-DD
Trial statistician	[@name]	[Reference]	YYYY-MM-DD
Principal investigator (each site)	[@name]	[Reference]	YYYY-MM-DD

Revision history

Version	Date	Author	Change summary	Amendment type
0.1	YYYY-MM-DD	[@name]	First draft for sponsor review	Not applicable
1.0	YYYY-MM-DD	[@name]	Approved for submission to ethics committee	Not applicable
2.0	YYYY-MM-DD	[@name]	Example: Added two sites; extended recruitment by 6 months	Substantial

Administrative information
Open science
Introduction
Methods: patient and public involvement, trial design, participants, interventions and outcomes
Methods: assignment of interventions
Methods: data collection, management and analysis
Methods: monitoring
Ethics
Appendices

1. Administrative information

This section identifies the trial, the protocol version and the people and committees responsible for it.

1.1 Title and structured summary (items 1a, 1b)

Title: [Descriptive title stating the design, population and interventions, identifying the document as a protocol, for example "A multicentre, double-blind, placebo-controlled randomised trial of [intervention] for [condition] in adults: study protocol"].

Structured summary: A short summary of the trial design and methods that includes the items of the WHO Trial Registration Data Set.

Item	Value
Primary registry and number	[Registry, number]
Sponsor	[Organisation]
Health condition	[Condition]
Interventions	[Intervention and comparator]
Key eligibility	[Main inclusion and exclusion criteria]
Study type and design	[Randomised, parallel, 1:1, double-blind]
Target sample size	[190]
Primary outcome	[Outcome and time point]
Date of first enrolment	YYYY-MM-DD (planned)

1.2 Protocol version (item 2)

Version [1.0], dated [YYYY-MM-DD], identifier [PROT-ACRONYM-001]. See the revision history above.

1.3 Roles and responsibilities (items 3a to 3d)

Role or committee	Members or organisation	Responsibilities
Protocol contributors	[Names, affiliations, roles]	[Who wrote which parts]
Sponsor	[Organisation, contact name, email]	[Overall responsibility, insurance]
Role of sponsor and funders	[Statement]	Example: No role in design, analysis or reporting; no right to veto publication
Coordinating centre	[Clinical trials unit]	[Day-to-day management]
Trial steering committee	[Independent chair and members]	[Oversight; decides on continuation]
Endpoint adjudication committee	[Members or "not applicable"]	[Blinded review of primary events]
Data management team	[Team]	[Database, coding, cleaning]
Data monitoring committee	[Members]	See section 7.1

2. Open science

These items make the trial and its materials findable and its funding and interests transparent.

2.1 Trial registration (item 4)

Item	Value
Registry	[ClinicalTrials.gov / ISRCTN / EU CTIS / national registry]
Registration number and URL	[Number, link]
Date of registration	YYYY-MM-DD
If not yet registered	[Name of intended registry]

2.2 Protocol and statistical analysis plan (item 5)

The protocol will be available at [journal / registry / repository link]. The statistical analysis plan (SAP) will be finalised before unblinding and published at [link] by [YYYY-MM-DD].

2.3 Data sharing (item 6)

Material	Plan	Where	When	Access conditions
De-identified individual participant data	Example: Shared	[Repository]	6 months after primary publication	Approved proposal and data use agreement
Data dictionary	[Shared / not shared]	[Repository]	[When]	[Conditions]
Statistical code	Example: Shared	[Code repository]	At publication	Open licence
Other materials (case report forms, intervention manual)	[Plan]	[Where]	[When]	[Conditions]

2.4 Funding and conflicts of interest (items 7a, 7b)

Item	Detail
Sources of funding	[Funder, grant number]
Other support	[Supply of drugs or devices]
Conflicts of interest	[Financial and other interests of principal investigators and steering committee members]

2.5 Dissemination policy (item 8)

Audience	Plan
Participants	Example: Plain-language summary mailed within 12 months of trial completion
Trial registry	[Results posted within the registry's required time frame]
Healthcare professionals	[Journal publication regardless of result; conference presentation]
Public and other groups	[Patient charity newsletter, press release]
Authorship	[Criteria, for example ICMJE; no professional writers]

3. Introduction

The introduction explains why this trial is needed now.

3.1 Background and rationale (item 9a)

[Summarise the condition, current care and the evidence gap, including published and unpublished studies on the benefits and harms of each intervention. Cite the relevant systematic review or explain why none exists.]

3.2 Choice of comparator (item 9b)

[Explain why the comparator (placebo, usual care, active treatment) is appropriate and ethical.]

3.3 Objectives (item 10)

ID	Objective	Hypothesis
OBJ-01	Example: Determine whether [intervention] reduces [primary outcome] at 12 weeks compared with placebo	Superiority, minimal important difference 5 points
OBJ-02	[Secondary benefit objective]	[Hypothesis]
OBJ-03	Compare the frequency of [specified harms] between arms	Descriptive

4. Methods: patient and public involvement, trial design, participants, interventions and outcomes

This section covers involvement, design, population, interventions, outcomes, timeline, sample size and recruitment.

4.1 Patient and public involvement (item 11)

Stage	Who	Activity	Influence on the protocol
Design	Example: 6 people with [condition] in a lived-experience panel	Two workshops on outcomes and visit burden	Patient-reported primary outcome; visits reduced from 6 to 4
Conduct	[Who]	[Review of participant information, steering committee membership]	[Influence]
Reporting	[Who]	[Co-writing the plain-language summary]	[Influence]

4.2 Trial design (item 12)

[Type of trial (parallel, crossover, factorial, cluster), allocation ratio and framework (superiority, equivalence, non-inferiority, exploratory). For example: multicentre, randomised, double-blind, placebo-controlled, parallel-group superiority trial, 1:1 allocation.]

4.3 Trial setting (item 13)

[Settings (community clinics, academic hospitals) and locations (countries, number of sites). Give the list of sites in appendix E or say where it can be obtained.]

4.4 Eligibility criteria (items 14a, 14b)

Participants: inclusion criteria

[Age 18 years or older]
[Diagnosis of [condition] confirmed by [method]]
[Severity above threshold]
[Able and willing to give written informed consent]

Participants: exclusion criteria

[Known hypersensitivity to the investigational product]
[Pregnancy or breastfeeding]
[Participation in another interventional trial within 30 days]

Sites and intervention providers (if applicable): [for example sites must see at least 20 eligible patients a year; therapists need two years' experience and completion of the trial training course].

4.5 Intervention and comparator (items 15a to 15d)

Element	Intervention arm	Comparator arm
Description (15a)	[Product, dose, route, frequency, duration, who administers]	[Placebo or comparator details]
Additional materials (15a)	[Intervention manual, link]	[Link]
Discontinuation or modification (15b)	Example: Halve dose for grade 2 toxicity; stop for grade 3 or above or on participant request	[Same rules]
Adherence strategies and monitoring (15c)	[Pill counts at each visit, diary, reminder messages]	[Same]
Concomitant care permitted (15d)	[List]	[List]
Concomitant care prohibited (15d)	[List]	[List]

4.6 Outcomes (item 16)

ID	Outcome	Variable	Metric	Aggregation	Time point
OUT-P1	Example: Symptom severity (primary)	[Validated scale score, 0-50]	Change from baseline	Mean	Week 12
OUT-S1	Response	Score reduction of at least 50%	Final value	Proportion	Week 12
OUT-S2	[Quality of life]	[Instrument]	[Metric]	[Aggregation]	[Weeks 4, 12, 26]

4.7 Harms (item 17)

Aspect	Approach
Definitions	Example: Adverse events coded with MedDRA [version]; graded with [CTCAE version]
Systematic assessment	[Structured symptom checklist at every visit; laboratory tests at weeks 4 and 12]
Non-systematic assessment	[Spontaneous reports by participants at any time]
Serious adverse events	Example: Reported to the sponsor within 24 hours of site awareness
Suspected unexpected serious adverse reactions	[Sponsor to regulator and ethics committee within the regulatory time frame]

4.8 Participant timeline (item 18)

The schedule of enrolment, interventions and assessments is shown below (X = performed).

Procedure	Screening (day -14 to -1)	Baseline (day 0)	Week 4 (+/- 3 days)	Week 12 (+/- 7 days)	Week 26 (+/- 14 days)
Eligibility screen	X
Informed consent	X
Randomisation		X
Medical history	X
Physical examination	X	X		X
[Primary outcome measure]		X	X	X	X
[Blood tests]	X		X	X
Study drug dispensed		X	X
Adherence check			X	X
Harms assessment		X	X	X	X
Concomitant medication review	X	X	X	X	X

4.9 Sample size (item 19)

For a two-arm comparison of means with equal allocation:

n_{\text{per arm}} = \frac{2\,\sigma^{2}\,\left(z_{1-\alpha/2} + z_{1-\beta}\right)^{2}}{\Delta^{2}}, \qquad n_{\text{adjusted}} = \frac{n_{\text{per arm}}}{1 - d}

where $d$ is the expected drop-out proportion. Example: $\sigma = 10$ , $\Delta = 5$ , two-sided $\alpha = 0.05$ , power 90% gives 85 per arm; with $d = 0.10$ , the target is 95 per arm (190 in total).

Assumption	Value	Source
Standard deviation	[10]	[Pilot data / published trial]
Minimal important difference	[5]	[Reference]
Alpha / power	[0.05 / 90%]	[Rationale]
Drop-out	[10%]	[Reference]

4.10 Recruitment (item 20)

Item	Plan
Sources	[Clinic lists, referrals, registries, advertising approved by ethics]
Expected rate	Example: 4 participants per site per month across 8 sites
Recruitment period	[18 months]
Feasibility evidence	[Audit of eligible patients in prior year]
Contingency	[Additional sites if below 70% of target at month 6]

5. Methods: assignment of interventions

This section describes how participants are allocated and how bias is prevented.

5.1 Sequence generation (items 21a, 21b)

[Who generates the sequence and how (for example an independent statistician using computer-generated random numbers), the type of randomisation (simple or restricted) and stratification factors. Details of any blocking are held in a separate restricted document.]

5.2 Allocation concealment mechanism (item 22)

[Mechanism, for example a central 24-hour web randomisation service, with steps that keep the sequence hidden until assignment.]

5.3 Implementation (item 23)

Task	Responsible	Access to sequence?
Generates the sequence	[Independent statistician]	Yes
Enrols participants	[Site investigators]	No
Assigns interventions	[Randomisation system]	System only

5.4 Blinding (items 24a to 24c)

Group	Blinded	Method
Participants	[Yes / No]	[Matching placebo]
Care providers	[Yes / No]	[Method]
Outcome assessors	[Yes / No]	[Method]
Data analysts	[Yes / No]	[Coded arms]

Unblinding: Example: The site investigator may unblind a single participant through the randomisation system when knowledge of allocation is needed for clinical care. Each unblinding is logged and reported to the trial manager within 24 hours.

6. Methods: data collection, management and analysis

This section covers data collection, data management and the planned analyses.

6.1 Data collection methods (items 25a, 25b)

Data	Instrument	Collected by	Quality measures
[Primary outcome]	[Validated scale, reference]	[Trained blinded assessor]	Example: Assessor certification, 10% double scoring
[Laboratory values]	[Central laboratory]	[Site nurse]	[Accredited laboratory]
[Harms]	[eCRF form]	[Investigator]	[Source verification]

Retention (item 25b): [Plans to promote complete follow-up, for example visit reminders and travel reimbursement, and the outcome data to be collected from participants who discontinue or deviate from the intervention.]

6.2 Data management (item 26)

[Describe data entry (for example a validated electronic data capture system), coding, security and storage, double entry or range checks, query handling and database lock procedure. Refer to the data management plan and say where it can be obtained.]

6.3 Statistical methods (items 27a to 27d)

Item	Method
Comparison of outcomes, including harms (27a)	Example: Linear mixed model, adjusted for baseline score and stratification factors; harms summarised with risk differences
Analysis populations (27b)	[All randomised participants in allocated arm; per-protocol as sensitivity]
Missing data (27c)	[Multiple imputation; sensitivity analyses under missing not at random]
Additional analyses (27d)	[Prespecified subgroups with interaction tests; sensitivity analyses]

7. Methods: monitoring

This section covers the data monitoring committee, interim analyses and trial monitoring.

7.1 Data monitoring committee (items 28a, 28b)

Item	Detail
DMC composition	[Independent clinician chair, second clinician, statistician]
Independence from sponsor and funder	[Statement; competing interests declared]
Role and reporting structure	[Reports recommendations to the trial steering committee]
Charter	[Reference and where it can be obtained]
Interim analyses	Example: One efficacy and safety review after 50% of participants complete week 12, Haybittle-Peto boundary
Access to interim results	[DMC and unblinded statistician only]
Final decision to terminate	[Trial steering committee on DMC recommendation, with sponsor]

7.2 Trial monitoring (item 29)

[Frequency and procedures for monitoring trial conduct, for example a risk-based monitoring plan with central statistical monitoring monthly, on-site visits at each site after the first 3 participants and then annually, and 100% source data verification of consent and primary outcome. If there is no monitoring, explain why.]

8. Ethics

This section covers ethical approval, amendments, consent, confidentiality and post-trial care.

8.1 Research ethics approval (item 30)

[Plans for seeking approval from research ethics committees or institutional review boards, with references when obtained.]

8.2 Protocol amendments (item 31)

[How important protocol modifications will be communicated to investigators, ethics committees, regulators, participants, registries and journals.]

8.3 Consent or assent (items 32a, 32b)

[Who obtains informed consent or assent from potential participants or authorised proxies, and how; arrangements for participants who lack capacity; additional consent provisions for use of participant data and biological specimens in ancillary studies.]

8.4 Confidentiality (item 33)

[How personal information about potential and enrolled participants will be collected, shared and maintained to protect confidentiality before, during and after the trial, in line with applicable privacy law.]

8.5 Ancillary and post-trial care (item 34)

[Provisions for ancillary and post-trial care and for compensation of those harmed by participation.]

9. Appendices

Supporting documents that accompany the protocol:

Appendix	Content
A	Informed consent form and participant information sheet (version and date)
B	Biological specimens: collection, laboratory evaluation and storage plan
C	Completed SPIRIT 2025 checklist with page references
D	Case report forms
E	List of sites
F	Glossary: [AE adverse event, DMC data monitoring committee, eCRF electronic case report form, PPI patient and public involvement, SAE serious adverse event]

Standard and licence note

Based on the SPIRIT 2025 Statement: Chan A-W, Boutron I, Hopewell S, Moher D, Schulz KF, et al., SPIRIT 2025 statement: updated guideline for protocols of randomised trials, BMJ 2025;389:e081477 (https://doi.org/10.1136/bmj-2024-081477) and parallel publications, with the checklist at https://www.consort-spirit.org. The SPIRIT 2025 statement and checklist are published open access under the Creative Commons Attribution licence (CC BY 4.0, https://creativecommons.org/licenses/by/4.0/). This template follows the order of its 34 items (including the new open science section and the patient and public involvement item), paraphrased in original text, and reproduces no checklist wording; use the official checklist and its explanation and elaboration for the normative items. SPIRIT 2025 replaces SPIRIT 2013. This is a document format, not clinical, statistical or regulatory advice; follow local privacy law and your institution's documentation policy. Template licence: MIT.