How ICH E3’s sections and annexes fit together

ICH E3 lays out a clinical study report in sixteen sections, from those that identify the report to its appendices, and closes with eight annexes, most of them labelled as examples.

The sections in order

A clinical study report tells the story of one clinical study: why it matters, how it works, who takes part, and what the evidence shows. ¹

Each of the first twelve sections answers one question about the study or its report: ²

Section	The question it answers
1. Title page	Which study and report is this?
2. Synopsis	What does the whole study show?
3. Table of contents	Where is each part of the evidence?
4. List of abbreviations and definition of terms	What do the words, letters, and units mean?
5. Ethics	How are participants’ rights and welfare protected?
6. Investigators and study administrative structure	Who carries out the study and takes responsibility?
7. Introduction	Why does this study belong in the development programme?
8. Study objectives	What does the study aim to find out?
9. Investigational plan	How does the study investigate those questions?
10. Study patients	What happens to the people who enter the study?
11. Efficacy evaluation	What evidence addresses the intended benefits?
12. Safety evaluation	What unwanted effects and other safety findings appear?

^{3, 2}

Sections 1–4 identify the report and help the reader navigate it, and the synopsis comes near the beginning because it gives readers an overview of the whole report. ² Sections 5–6 establish ethical oversight and responsibility, sections 7–9 connect the reason for the study to its objectives and methods, and sections 10–12 follow its conduct and findings. ² Sections 13–16 close the report with the discussion and overall conclusions, the tables, figures and graphs referred to but not included in the text, the reference list and the appendices. ^{3, 4}

Changing the order and numbering

ICH E3 recommends that each report consider every topic it describes unless the topic is clearly not relevant, and it allows the sequence and grouping of the topics to change where another arrangement is more logical for a particular study. ^{5, 6}

ICH E3 numbers its sections from 1 to 16, but the sections of an actual report need not carry the same numbers. ⁴ One view holds that the first six headings should not be numbered and that the numbering should logically start with 1. Introduction: ⁴

Title page	3. Investigational plan
Synopsis	4. Study patients
Table of contents	5. Efficacy evaluation
Glossary and abbreviations	6. Safety evaluation
Ethics	7. Discussion/conclusions
Administrative structure	8. Tables/figures not in text
1. Introduction	9. References
2. Study objectives	10. Appendices

⁴

The annexes

ICH E3 closes with eight annexes, most of them labelled as examples. ³

Annex	What it shows
I	Synopsis (example)
II	Signatures of the principal or coordinating investigators or of the sponsor’s responsible medical officer (example)
IIIa, IIIb	Study design and schedule of assessments (examples)
IVa, IVb	Disposition of patients (examples)
V	Listing of patients who discontinued therapy (example)
VI	Listing of patients and observations excluded from efficacy analysis
VII	Number of patients excluded from efficacy analysis (example)
VIII	Guidance for the statistical and analytical issues of Section 11.4.2 and for Appendix 16.1.9, the documentation of statistical methods

³

ICH E3’s entry for Appendix 16.1.8, audit certificates (if available), refers to Annexes IVa and IVb. ³