ICH M11 Protocol Template (CeSHarP), Section by Section
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ICH M11 is the harmonised standard for the structure and content of a clinical trial protocol. Its full name is the Clinical electronic Structured Harmonised Protocol, shortened to CeSHarP. Before M11, ICH had no standard format for a protocol. Each sponsor used its own, which made protocols hard to search, review and compare.
M11 is three documents, not one. They are a guideline, a protocol template and a technical specification. The template says where each piece of content goes. The technical specification says how each piece is defined as data, so that protocols can be exchanged electronically.
Status and dates
| Date | Event |
|---|---|
| 27 September 2022 | ICH Assembly endorses the draft at Step 2 and releases it for consultation |
| 3 February 2025 | Updated Step 2 draft of the technical specification, for a second consultation |
| 19 November 2025 | ICH Assembly adopts the guideline, template and technical specification at Step 4 |
| 11 December 2025 | EMA's CHMP adopts the guideline. EMA published it on 15 December 2025. |
| 5 May 2026 | ICH publishes its overview of the three documents |
| 21 and 22 May 2026 | FDA issues the final guidance (listed 21 May, Federal Register notice 22 May, 91 FR 30310, docket FDA-2022-D-3054) |
| 11 June 2026 | EMA's date for the guideline to come into effect |
| 4 November 2026 | Health Canada notice: phase 1 (document-based) starts now. Phase 2 (structured data) has no date. |
FDA's guidance finalizes its December 2022 draft and its June 2025 draft of the technical specification. It covers CDER and CBER. Like all FDA guidance, it is nonbinding. EMA's guideline page states no mandate and no transition period.
Health Canada has published the most specific plan. Its notice of 4 November 2026 sets two phases. Phase 1, effective on publication, covers protocols that follow the M11 structure and content in PDF or DOCX. Phase 2 covers submission in structured formats such as JSON or XML. Health Canada will introduce Phase 2 only after it publishes technical specifications, guidance and timelines, and it gives no date.
Japan. PMDA has posted the Step 4 documents, with training modules. I found no Japanese implementation notice or date.
I found no implementation notice from NMPA, MHRA or Swissmedic. ICH keeps a per-region implementation tracker on its site, but it loads through scripts and I could not read it. Check it before you plan a filing for a specific region.
FDA has tested the exchange. In a research collaboration run on FDA's precisionFDA platform, sponsors prepared M11 protocols as DOCX and PDF and as machine-readable FHIR JSON, and exchanged them with FDA. The M11 rapporteur, an FDA CBER official, presented the pilot in October 2024, speaking for himself and not for FDA. It was a pilot, not a submission requirement.
Scope
The template and specification apply to interventional clinical trials of medicinal products, in all phases and therapeutic areas. ICH defines "trial intervention" to include pharmaceuticals, biologics, vaccines, drug-device combinations developed as a drug, and cell or gene therapy products where applicable.
The guideline limits itself. It does not specify how to develop or maintain a protocol. It does not replace other guidelines that set protocol content. It gives no advice on designing a good trial. It sets common instructions for placing content that other guidelines already require, plus the technical attributes needed to exchange it.
Observational studies are outside the template's scope.
The three documents
The guideline. A short document that states the purpose and design principles. The template's principles are: build common core content, serve the needs of stakeholders, define content for electronic exchange, design for content reuse, and keep flexibility. The specification's principles include promoting structured common core content and enabling an open, nonproprietary exchange standard.
The template. A protocol skeleton with headings, instructional text and field markers. Section 0 explains conventions and is deleted from the final protocol.
The technical specification. A table that lists every heading and data element in the template with attributes: term, data type, whether it is a heading, data or value, a definition code, user guidance, conformance (for example required or optional), cardinality, its place in the table of contents, permitted values and business rules.
Template conventions
The template marks the kind of text each part is. Authors must know the markers, because they decide what stays in the final protocol.
| Marker | Meaning |
|---|---|
| Black text | Universal text. Appears in all protocols. |
| Black text in {braces} | Conditional universal text. Appears if it applies to the trial, sometimes as a choice between options. |
| Blue text | Optional text or optional heading. May be changed, deleted or replaced. |
| [Square brackets], grey shading | Controlled terminology. A field with pre-defined valid values, which becomes a pick list in the electronic form. |
| <Chevrons>, grey shading | Insertion point. Replace with trial content. |
| Red text | Instructional text. Remove before finalising. |
Heading rules are strict at the top. Level 1 headings cannot be deleted, modified or added. Level 2 headings in black cannot be deleted or modified. If a heading does not apply, keep it and enter "Not applicable". New level 2 headings go at the end of the parent section so the standard numbering holds.
To finalise, delete Section 0, update the table of contents, remove unused optional text and instructional text, restyle remaining optional text, and remove the brackets once you have made your selections.
The template also fixes some vocabulary. It says "clinical trials" in place of "clinical studies", "participant" in place of subject or patient, and "trial intervention" for any prespecified therapeutic, prophylactic or diagnostic agent. "Masking" is allowed as an alternative to "blinding".
The sections
The template puts the information an investigator needs to run the trial first: synopsis, schema and schedule of activities. Reference detail sits in appendices, which carry the same weight as the main body.
| Section | Content | Points to check |
|---|---|---|
| Title page | Confidentiality statement, full title, acronym, sponsor protocol identifier, version and date, amendment identifier and scope, product codes and names, trial phase, short title, sponsor, regulatory and registry identifiers, sponsor approval, signatory, medical expert contact | Element order is preserved. The short title should work as a registry brief title. Identifiers include EU CT, FDA IND, IDE, jRCT, NCT, NMPA IND and WHO/UTN numbers. |
| Amendment details | Statement of amendment history, current amendment table and reasons | Include approximate enrollment at the time of sponsor approval |
| 1 Protocol summary | 1.1 synopsis (1.1.1 objectives and estimands in plain language, 1.1.2 overall design table), 1.2 trial schema, 1.3 schedule of activities | The SoA lists every procedure per visit and all participant contact, with allowed windows |
| 2 Introduction | 2.1 purpose of trial, 2.2 assessment of risks and benefits (risk summary and mitigation, benefit summary, overall assessment) | Do not restate objectives or the investigator's brochure |
| 3 Trial objectives and associated estimands | Primary, secondary and exploratory objectives, each with its estimand | Align with ICH E9(R1) |
| 4 Trial design | 4.1 description and stakeholder input, 4.2 rationale (estimands, intervention model, control type, duration, adaptive design, interim analysis, other), 4.3 stopping rules, 4.4 start and end of trial, 4.5 access after the trial | Each rationale subsection is separate |
| 5 Trial population | Description and rationale, inclusion, exclusion, contraception, lifestyle restrictions, screen failure and rescreening | |
| 6 Trial intervention and concomitant therapy | 6.1 to 6.10: description, dose rationale, administration, dose modification, overdose, preparation and storage, assignment, randomisation and blinding, adherence, non-investigational intervention, concomitant therapy | |
| 7 Discontinuation and withdrawal | Permanent and temporary discontinuation, rechallenge, withdrawal from the trial, loss to follow-up | |
| 8 Trial assessments and procedures | Screening and baseline, efficacy, safety, pharmacokinetics, biomarkers, immunogenicity, resource use and health economics | |
| 9 Adverse events and related safety | Definitions, collection and reporting, adverse events of special interest, disease-related events, pregnancy, special safety situations | |
| 10 Statistical considerations | General considerations, analysis sets, baseline, primary, secondary and exploratory analyses, safety, interim analyses, multiplicity, sample size | Primary analysis covers the method, handling of data for the estimand, and missing data |
| 11 Trial oversight and other general considerations | 11.1 regulatory and ethical, 11.2 oversight, 11.3 informed consent, 11.4 committees, 11.5 insurance, 11.6 risk-based quality management, 11.7 data governance, 11.8 data protection, 11.9 source records, 11.10 protocol deviations, 11.11 early site closure, 11.12 data dissemination | |
| 12 Appendix: supporting details | 12.1 clinical laboratory tests, 12.2 country and region-specific differences, 12.3 prior protocol amendments | Prior amendments in reverse chronological order |
| 13, 14 Appendices | Glossary and abbreviations, references |
The overall design table
Section 1.1.2 is a table of fields that become structured data. The fields include the intervention and its model, the control type and description, the intervention assignment method, stratification, drug-device combination indicator, population type, population diagnosis or condition (MedDRA preferred terms), minimum and maximum age, site distribution and geographic scope, master protocol, adaptive design, number of arms, trial blind schema and blinded roles, number of participants, planned duration, and committees. Most take a value from a fixed list.
The technical specification and structured protocols
A structured protocol keeps content as defined data elements as well as narrative. "Trial phase", for example, is a field with valid values. It is not a phrase buried in a paragraph. Software can then read the protocol, check it and reuse it in downstream systems, such as registries, trial management and data capture.
The specification defines each element with:
- Attributes. Each element has a data type, conformance rule, cardinality (how many times it can occur) and a place in the protocol hierarchy.
- Definition codes. Each concept gets a code in the NCI Thesaurus. The M11 terminology is published as NCI subset C217023.
- Object identifiers. Each code list has an ICH OID, published on the ICH electronic standards page. The ICH overview gives the trial phase code list as an example: C217045, OID 2.16.840.1.113883.3.989.2.3.1.18.
The guideline says the aim is to enable an open, nonproprietary data model and exchange message standard. M11 does not itself define a file format.
Controlled terminology
ICH and CDISC signed an agreement for governing M11 controlled terminology. The terminologies are curated and maintained through a unified process, reviewed publicly, and published for free after CDISC's public review. Pick lists in the template, such as trial phase, intervention model, control type and blinded roles, draw on these code lists. Population diagnosis uses MedDRA preferred terms.
M11 and ICH E6(R3)
ICH E6(R3) Annex 1 lists, in Appendix B, the topics a protocol should generally include. M11 does not add topics. It fixes where they sit. The mapping below is my own reading, not an official crosswalk.
| E6(R3) Appendix B topic | M11 location |
|---|---|
| B.1 General information | Title page |
| B.2 Background information | 2 Introduction, 6.1 |
| B.3 Objectives and purpose | 3 Objectives and estimands |
| B.4 Trial design | 1.2, 1.3, 4, 6.6, 6.7 |
| B.5 Selection of participants | 5 |
| B.6 Discontinuation and withdrawal | 7 |
| B.7 Treatment and interventions | 6 |
| B.8 Assessment of efficacy | 8.3 |
| B.9 Assessment of safety | 8.4, 9 |
| B.10 Statistical considerations | 10 |
| B.11 Direct access to source records | 11.9 |
| B.12 Quality control and assurance | 11.6, 11.10 |
| B.13 Ethics | 11.1, 11.3 |
| B.14 Data handling and record keeping | 11.7, 11.9 |
| B.15 Financing and insurance | 11.5 |
| B.16 Publication policy | 11.12 |
Two parts of M11 reflect the E6(R3) quality-by-design approach. Section 11.6 asks for the critical-to-quality factors, associated risks and mitigation, or a pointer to where they are maintained as the trial learns from emerging data. Section 11.10 asks for plans to detect, review and report deviations. See protocol deviation. Section 11.9 on source records connects to the trial master file and to electronic record expectations in 21 CFR Part 11.
The template also tells authors to use ICH E9(R1) when writing objectives and estimands, and ICH E9 for the statistical section.
CDISC USDM and digital data flow
The Unified Study Definitions Model (USDM) is CDISC's logical model for a study's design, built within the Digital Data Flow initiative with TransCelerate. It is the model most often linked with M11. CDISC released USDM version 4.0 on 3 June 2025, with continued alignment to the M11 template. CDISC also publishes conformance rules for USDM. Example protocols in the USDM come with JSON files.
The relationship in short: M11 defines what a protocol contains and how each element is coded. USDM is one way to hold that content as data. A tool can render a digital protocol into the M11 template, or read a protocol document into the USDM. I found no regulator statement that USDM files are required or accepted for submission. Health Canada's Phase 2 names JSON or XML and does not name USDM.
Amendments
M11 gives amendments their own structure. The title page carries the amendment identifier and scope (global, or limited to a country, region or site). An amendment details page states whether the protocol has been amended, shows the approximate enrollment when the sponsor approved it, and records primary and secondary reasons. A summary of changes for the current amendment sits before the table of contents. Section 12.3 lists prior amendments, newest first.
Author checklist
Use this to check a draft against the template.
- Section 0 and all red instructional text are deleted.
- Title page elements are in template order, with every identifier available at finalisation.
- No level 1 or level 2 heading is deleted, reworded or added. Unused headings read "Not applicable".
- The synopsis states objectives and estimands in plain language.
- Every field in the overall design table has a value from its list.
- The schedule of activities covers every visit, contact and procedure, with windows.
- Each primary and secondary objective has an estimand, and section 10 handles data and missing data for each primary estimand.
- Section 11.6 names critical-to-quality factors, or says where they are kept.
- Section 11.10 states how deviations are detected and reported.
- Country-specific differences go in 12.2, or in a stated addendum.
- Prior amendments are listed newest first in 12.3.
- Terminology uses "participant", "trial intervention" and "clinical trial" as the template does.
Limits of M11
It does not set the content standard for observational studies, define a file format, tell a sponsor how to design a trial, or change what E6(R3), E8(R1) or E9(R1) require. It does not check a protocol for you. A heading-by-heading comparison against the template is a good use of software. The judgment about whether the content is right stays with the team.
Frequently asked questions
What is ICH M11?
The ICH guideline, with a protocol template and a technical specification, that standardises the structure and content of clinical trial protocols and defines them as data for electronic exchange. Its full name is the Clinical electronic Structured Harmonised Protocol (CeSHarP).
When was ICH M11 finalised?
The ICH Assembly adopted it at Step 4 on 19 November 2025. EMA's CHMP adopted it on 11 December 2025, with an effective date of 11 June 2026. FDA issued the final guidance in May 2026.
Is the M11 template mandatory?
FDA's guidance is nonbinding, and EMA's page states no mandate. Health Canada's notice of 4 November 2026 asks for M11-structured protocols in PDF or DOCX now and defers structured data (JSON or XML) to a later phase with no date. I found no regulator date for mandatory structured submission.
What trials does M11 cover?
Interventional clinical trials of medicinal products in all phases and therapeutic areas, including biologics, vaccines, drug-device combinations developed as a drug, and cell and gene therapy products where applicable.
What is the M11 technical specification?
The document that defines each template heading and data element with attributes such as data type, conformance, cardinality, definition code and permitted values, so protocol content can be exchanged electronically.
How does M11 relate to ICH E6(R3)?
E6(R3) Appendix B lists what a protocol should generally include. M11 sets where each topic goes. M11 section 11.6 also reflects E6(R3)'s focus on critical-to-quality factors.
How does M11 relate to CDISC USDM?
USDM is CDISC's model for holding study design as data. Version 4.0 (June 2025) was aligned with M11. M11 does not require it.
What is controlled terminology in M11?
Fixed lists of valid values for fields such as trial phase and control type. CDISC and ICH maintain them under a joint agreement, and they are published in the NCI Thesaurus.