The ICH E3 guideline

This branch covers the clinical study report as the ICH E3 guideline lays it out. Its parts divide by the report’s sixteen sections, in E3’s order from the title page to the appendices, after two parts on the guideline as a whole: how those sections and its annexes fit together, and how far its headings bind the writer. Each section’s part also covers how CORE Reference changes that section, where it does. Where a report’s requirements come from, what the CORE Reference manual is, the TransCelerate common template and the revision of E3 and E6 are left to the branch’s neighbours.

• How ICH E3’s sections and annexes fit together — the sixteen sections in order, the latitude to change their sequence, grouping or numbering, and what each of the eight annexes shows.
• Reading ICH E3 as guidance rather than a template — E3 as a framework for the report, the dispute over reading its headings as a template, how medical writers obtained the 2012 questions and answers that settled it, and the new sections and appendices they allow for material E3 does not address.
• 1. Title page — the fourteen items that identify the study, its treatment, who is responsible for it and which of its reports this is.
• 2. Synopsis — the brief summary of the whole study that Section 2 asks for, the fields of the Annex I example, what makes a synopsis work, and how CORE Reference changes it.
• 3. Table of contents — locating the report’s sections and displays and its supporting material, and what serves as locating information besides a page number.
• 4. Abbreviations and terms — listing the abbreviations, and defining the specialised terms and measurement units, so that their meanings stay recoverable.
• 5. Ethics — independent ethics review, the ethical conduct of the study, and patient information and consent.
• 6. Investigators and study administrative structure — the study’s administrative structure, the investigators and other important participants listed in Appendix 16.1.4, and the signatures in Appendix 16.1.5.
• 7. Introduction — the study’s place in the development programme, its critical features, the guidance and regulatory discussions behind the protocol, and an example introduction.
• 8. Study objectives — the study’s overall purpose, how objectives tie to endpoints and to the rest of the report, primary, secondary and exploratory objectives, the subjects an objective can address, and what makes an objective clear.
• 9. Investigational plan — the design and its rationale, the population, treatments, variables, data quality assurance, statistical plans and sample size, changes after the study began, and CORE Reference’s changes to the section.
• 10. Study participants — the disposition of patients, protocol deviations, the listings of the participants concerned, and the sections CORE Reference moves into Section 10.
• 11. Efficacy evaluation — the data sets analysed, baseline characteristics, treatment compliance, efficacy results and individual participant data, the section under CORE Reference, and its order in a phase I oncology report.
• 12. Safety evaluation — extent of exposure, adverse events, deaths and serious and other significant events with their narratives, laboratory, vital-sign and other safety observations, safety conclusions, and how CORE Reference and an anticancer study adapt the section.
• 13. Discussion and overall conclusions — whether discussion and conclusions are merged, the relationship of risks and benefit, new and unexpected findings, the results in the light of other existing data, implications for individuals, at-risk groups and future studies, whether the discussion belongs in the report or the integrated summaries, and the shape of the conclusions.
• 14. Tables, figures and graphs — which displays stay in the text and which move to Section 14, what the section contains, and how every display identifies the patients it was generated from.
• 15. Reference list — which literature belongs in the list, the appendices that hold copies of the important publications, and the two accepted citation standards.
• 16. Appendices — the four appendix groups, what belongs in the appendices and what goes to other repositories, departures from E3’s appendix numbering, and finalising and compiling them.