# 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*.

<!--
Guidance: How to use this template
- Write the protocol before the first participant is enrolled and register
  the trial before enrolment. The registered record and protocol must agree.
- The "Item" references (for example "item 11") point to SPIRIT 2025
  checklist numbers so you can complete the checklist as you write.
- Fill sections 4.4 (outcomes) and 4.7 (sample size) early: they drive
  almost every other decision in the protocol.
- Every later change is a numbered amendment with ethics approval; never
  edit an approved version silently.
- Keep identifying participant data out of the protocol. Follow local
  privacy law (for example HIPAA or GDPR) and institutional policy.
-->

## Document control

<!-- Guidance: The protocol is a controlled document. Every approved version gets a number and date that appear on every page in the final format. -->

| 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| Status | [Draft / In review / Approved / Superseded] |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

<!-- Guidance: List every version, including amendments. Substantial amendments need ethics (and often regulatory) approval before implementation. -->

| 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 |

## Contents

<!-- Guidance: Keep in sync with the headings below. -->

1. [Administrative information](#1-administrative-information)
2. [Open science](#2-open-science)
3. [Introduction](#3-introduction)
4. [Methods: patient and public involvement, trial design, participants, interventions and outcomes](#4-methods-patient-and-public-involvement-trial-design-participants-interventions-and-outcomes)
5. [Methods: assignment of interventions](#5-methods-assignment-of-interventions)
6. [Methods: data collection, management and analysis](#6-methods-data-collection-management-and-analysis)
7. [Methods: monitoring](#7-methods-monitoring)
8. [Ethics](#8-ethics)
9. [Appendices](#9-appendices)

## 1. Administrative information

<!-- Guidance: Everything a reviewer needs to identify the trial and the people responsible for it. -->

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)

<!-- Guidance: Name the contributors and the sponsor, say what authority the sponsor and funders have over design, conduct, analysis and reporting, and describe each committee and group overseeing the trial. -->

| 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

<!-- Guidance: New in SPIRIT 2025: a section grouping registration, access to the protocol and statistical analysis plan, data sharing, funding and conflicts of interest, and dissemination. Plan these before enrolment, not after publication. -->

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)

<!-- Guidance: Say what will be shared, where, when and how to request it. Make sure the consent form (appendix A) permits the sharing you describe. -->

| 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

<!-- Guidance: Justify the trial. Cite a systematic review covering both benefits and harms of each intervention and explain why the comparator is appropriate. -->

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

<!-- Guidance: Define how patients and the public are involved, the design, who is eligible, what they receive, what is measured and when, and how many are needed. -->

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

### 4.1 Patient and public involvement (item 11)

<!-- Guidance: New in SPIRIT 2025. Describe who is or will be involved (patients, carers, members of the public), at which stages (design, conduct, reporting) and how their input is used. If there is none, say so and why. -->

| 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)

<!-- Guidance: Criteria must be checkable at screening. Include criteria for sites and for those delivering interventions where relevant. -->

**Participants: inclusion criteria**

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

**Participants: exclusion criteria**

1. [Known hypersensitivity to the investigational product]
2. [Pregnancy or breastfeeding]
3. [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)

<!-- Guidance: Describe each arm so it can be replicated: how, when and by whom it is given. Include criteria for discontinuing or modifying the allocated intervention, adherence strategies and permitted or prohibited concomitant care. -->

| 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)

<!-- Guidance: For each outcome give the measurement variable, the analysis metric (change from baseline, final value, time to event), the aggregation method (mean, proportion) and the time point. -->

| 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)

<!-- Guidance: SPIRIT 2025 gives harms more emphasis. Define harms and say how they will be assessed: systematically (structured questions or tests at set times) and non-systematically (spontaneous reports). Reporting routes to the sponsor and regulator belong here too. -->

| 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)

<!-- Guidance: The schedule table is the single most-used page of a protocol at sites. Mark each assessment with X at each visit, give visit windows, and include run-in and washout periods. SPIRIT 2025 provides an official figure template. -->

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)

<!-- Guidance: Show the calculation, the assumptions and their sources. Include allowance for attrition and any adjustment for clustering or interim analyses. -->

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)

<!-- Guidance: Describe how you will reach the target. Unrealistic recruitment plans are the most common cause of failed trials. -->

| 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

<!-- Guidance: Allocation concealment protects against selection bias; it is separate from blinding. Keep details such as block size in a separate document unavailable to enrolling staff. -->

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)

<!-- Guidance: Name who is blinded, how, and the circumstances and procedure for unblinding during the trial. -->

| 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

<!-- Guidance: Describe how data quality is assured from collection to analysis, including how participants are retained. -->

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)

<!-- Guidance: Summarise here and point to the statistical analysis plan, which must be finalised before unblinding. -->

| 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

<!-- Guidance: Describe who watches the accumulating data and how trial conduct is checked. -->

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

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

<!-- Guidance: Describe the composition and independence of the data monitoring committee (DMC), its role and reporting structure, competing interests and charter. If there is no DMC, justify why. Explain interim analyses, stopping guidelines and who decides on termination. -->

| 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

<!-- Guidance: Cover approvals, amendments, consent, confidentiality and care for participants. -->

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)

<!-- Guidance: Say who obtains consent or assent and how, including authorised proxies. Cover additional consent for data and biological specimens used in ancillary studies. -->

[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

<!-- Guidance: Attach materials that ethics committees and sites need. -->

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.