ICH E3, “Structure and Content of Clinical Study Reports,” is the International Council for Harmonisation guideline that defines a single, harmonised outline for the Clinical Study Report (CSR) — the integrated document that reports the methods and results of one clinical trial to a regulatory authority. It reached ICH Step 4 (final guideline) on 30 November 1995 and has not been substantively revised since; the FDA, EMA, and Japan’s PMDA all accept a CSR built to this structure, which is the point of the guideline: one core report, rather than a separate version negotiated with each regulator. ICH E3 sets out 16 numbered sections plus a four-part appendix structure, and specifies that the report must be integrated — clinical and statistical description, tables, and analyses combined into a single document, not a clinical narrative bolted onto a separate statistical report.
This page works through that structure section by section: the 16-part body, the appendices in section 16, the synopsis length rule, and how the finished CSR is positioned inside a Common Technical Document (CTD) submission. Last verified 2026-08-16 against the ICH Step 4 guideline text (database.ich.org/sites/default/files/E3_Guideline.pdf).
The ICH E3 16-Section CSR Template
Every ICH E3-compliant CSR follows the same numbered outline. The guideline is explicit that this is a required structure, not a suggested one — sponsors preparing a report for regulatory submission are expected to use these section numbers and headings directly.
| Section | Title | What it covers |
|---|---|---|
| 1 | Title Page | Study title, protocol/compound identifiers, sponsor, phase, dates, GCP compliance statement. |
| 2 | Synopsis | A standalone summary of the study, usually limited to about 3 pages (see below). |
| 3 | Table of Contents | Contents listing for the individual report, including tables, figures, and appendices. |
| 4 | List of Abbreviations and Definition of Terms | Every abbreviation and defined term used in the report. |
| 5 | Ethics | IEC/IRB approval, ethical conduct of the study, and patient information and consent (5.1-5.3). |
| 6 | Investigators and Study Administrative Structure | Sites, investigators, sponsor personnel, and other parties involved in running the study. |
| 7 | Introduction | Background and rationale for the study. |
| 8 | Study Objectives | The primary and secondary objectives the study was designed to answer. |
| 9 | Investigational Plan | The largest section: overall design (9.1), control group rationale (9.2), population selection and inclusion/exclusion criteria (9.3), treatments and blinding (9.4), efficacy/safety variables (9.5), data quality assurance (9.6), statistical methods and sample size (9.7), and any changes to the planned conduct or analyses (9.8). |
| 10 | Study Patients | Disposition of patients (10.1) and protocol deviations (10.2). |
| 11 | Efficacy Evaluation | Analysis data sets, baseline characteristics, compliance, efficacy results, and statistical/analytical issues (subgroups, dropouts, multiplicity, multicentre pooling). |
| 12 | Safety Evaluation | Extent of exposure, adverse event summaries and analysis, deaths/serious/other significant adverse events with narratives, clinical laboratory evaluation, vital signs, and overall safety conclusions. |
| 13 | Discussion and Overall Conclusions | The sponsor’s integrated interpretation of the efficacy and safety findings. |
| 14 | Tables, Figures and Graphs Referred to but Not Included in the Text | Demographic, efficacy, and safety data displays that support the text without being embedded in it. |
| 15 | Reference List | Publications and other references cited in the report. |
| 16 | Appendices | Study information, patient data listings, case report forms, and (for the US) individual patient data listings — see the next section. |
The Synopsis (Section 2): the 3-Page Rule
ICH E3 states that the synopsis “should be written to include numerical data, not just a description,” and that it is usually limited to about 3 pages. In practice the synopsis is what gets read most: it is often reproduced separately as a standalone summary for internal review, health-authority correspondence, and (in redacted form) public disclosure. ICH E3’s Annex I gives a worked example of an acceptable synopsis layout, covering the same ground as the full report — objectives, methodology, number of patients, diagnosis and criteria for inclusion, test product/dose/mode of administration, duration of treatment, criteria for evaluation, statistical methods, and a results/conclusion summary — compressed into a few pages of prose and tables.
CSR Appendices (Section 16): the 16.1-16.4 Structure
Section 16 is where ICH E3 diverges from a conventional document outline: most of its content is not written prose but a checklist of documents to attach or reference, organised into four groups.
| Appendix | Category | Representative contents |
|---|---|---|
| 16.1 | Study Information | Protocol and amendments; sample case report form; list of IECs/IRBs and consent forms; investigator list with brief CVs; investigator/sponsor signatures; batch listings; randomisation scheme and codes; audit certificates; statistical methods documentation; inter-laboratory standardisation methods; publications based on the study; other referenced publications. |
| 16.2 | Patient Data Listings | Discontinued patients; protocol deviations; patients excluded from the efficacy analysis; demographic data; compliance/drug-concentration data; individual efficacy response data; adverse event listings by patient; individual laboratory measurement listings (where a regulatory authority requires them). |
| 16.3 | Case Report Forms | CRFs for deaths, other serious adverse events, and withdrawals for adverse events; other CRFs submitted at a reviewer’s request. |
| 16.4 | Individual Patient Data Listings | US archival listings — a full patient-level data archive specific to US submissions. |
Because most of Section 16 is source documentation rather than narrative, sponsors typically assemble it in parallel with the main report body rather than at the end — the protocol, CRFs, randomisation codes, and audit certificates already exist as trial records, and Section 16’s job is to organise and reference them consistently, not create them from scratch.
Why “Integrated” Is the Operative Word
ICH E3’s introduction is explicit that the CSR it describes is an integrated full report: “the clinical and statistical description, presentations, and analyses are integrated into a single report.” The guideline goes on to specifically warn that this integrated report “should not be derived by simply joining a separate clinical and statistical report.” That distinction matters in practice — a CSR assembled by appending a biostatistics output package to a medical-writing narrative, rather than genuinely integrating the two into one analysis-and-interpretation flow, does not meet the guideline as written, even if every required section number is technically present.
Where the CSR Fits in a Regulatory Submission
A CSR built to the ICH E3 structure is not a standalone deliverable — it is the clinical-efficacy-and-safety component of a marketing application. In the ICH M4 Common Technical Document (CTD) format used to structure submissions such as an NDA, BLA, or Marketing Authorisation Application, individual study CSRs are filed within Module 5 (Clinical Study Reports), alongside the protocol, sample CRFs, and other Module 5 study-report documentation, while the sponsor’s cross-study synthesis of the same data appears separately in Module 2’s clinical summaries and Module 5’s tabular listing of all studies. A trial’s CSR is therefore written once, to the ICH E3 outline, and then referenced by that same structure across every region where the sponsor files.
CSR Transparency and Public Disclosure
Two regulatory transparency regimes govern what happens to a CSR after submission, and both use the ICH E3-structured document as their starting point:
- EMA Policy 0070 (“Publication of clinical data for medicinal products for human use”) requires proactive publication of clinical reports, including CSRs, submitted with centralised EU marketing authorisation applications, once a regulatory decision has been reached. Implementation began in the mid-2010s, was paused, and relaunched in September 2023 with expanded scope covering new active-substance applications, including negative opinions and withdrawn applications.
- Health Canada’s Public Release of Clinical Information (PRCI) guidance requires sponsors to make clinical information from drug and device submissions — including CSRs — publicly available, subject to redaction of confidential business and personal information. EMA and Health Canada run a joint work-sharing arrangement to reduce duplicated redaction effort on jointly reviewed applications.
In both regimes, the CSR that gets published is a redacted version of the same ICH E3-structured document filed with the regulator — not a separate public-facing summary. This is a distinct disclosure channel from a study results record on a public trial registry (see CASRAI’s Clinical Study Report (CSR) dictionary entry for how the two relate).
How CSR Structure Relates to Other ICH Guidelines
ICH E3 does not stand alone; several other guidelines determine what goes into the sections it defines:
- ICH E6(R3) (Good Clinical Practice) governs how the trial generating the CSR’s underlying data must have been conducted — a CSR reports on a study, but E6 is what makes that study’s data trustworthy in the first place. See also CASRAI’s ICH E6 vs. ICH E8 comparison and the guide to sponsor oversight of delegated CRO functions under ICH E6(R3).
- ICH E17 governs the design of a multi-regional trial whose pooled results are meant to support the same CSR across several regions at once — relevant to how Section 9 (Investigational Plan) is written when a study spans multiple regulatory jurisdictions.
- ICH E20 covers adaptive trial designs, which add reporting complexity to CSR Sections 9 and 11 (interim analyses, design changes) beyond a traditional fixed-design study.
- ICH E11A governs pediatric extrapolation, which affects how a CSR’s Section 8 (objectives) and Section 11 (efficacy evaluation) are framed when a study relies partly on extrapolated adult data.
Frequently Asked Questions
What is the ICH E3 structure for a Clinical Study Report?
It is a fixed 16-section outline — from the title page and synopsis through the investigational plan, efficacy and safety evaluations, discussion and conclusions, and a four-part appendix (Section 16) — defined by the ICH E3 guideline, “Structure and Content of Clinical Study Reports,” so that a single core report can be accepted by regulatory authorities across ICH regions.
Is there an official CSR template file?
ICH does not publish a fill-in-the-blank template document; it publishes the E3 guideline text itself, which functions as the template by specifying every required section number, heading, and (via Annexes I-VIII) worked examples of a synopsis, signature page, study-design schematic, and patient-disposition table. Sponsors, CROs, and medical-writing groups build their own document templates from this structure; the section numbers and headings are what must match, not a specific file format.
What appendices are required in a CSR?
Section 16 groups appendices into four categories: 16.1 Study Information (protocol, sample CRF, IEC/IRB and consent documentation, investigator CVs, randomisation codes, audit certificates, statistical methods documentation, related publications), 16.2 Patient Data Listings, 16.3 Case Report Forms, and 16.4 Individual Patient Data Listings (US archival listings). Not every item within 16.1-16.3 is required for every submission; several are qualified with “if available” or “when required by regulatory authorities” in the guideline text, so the exact appendix set is negotiated with the receiving regulator.
How long should the CSR synopsis be?
ICH E3 describes the synopsis as “usually limited to about 3 pages.” It is meant to stand alone as a numerical, results-oriented summary of the full report, not a restatement of the introduction.
Does every clinical trial need a full ICH E3 CSR?
Every trial intended to support a regulatory submission is expected to be reported using the ICH E3 structure, but the guideline itself notes that some of its detail is written with pivotal, controlled efficacy trials in mind; sponsors and regulators may agree on an abbreviated report for smaller or non-pivotal studies while keeping the same section numbering for consistency.
