CORE Reference is a user manual for writing clinical study reports based on the ICH E3 guideline. The project was developed by the European Medical Writers Association and the American Medical Writers Association to make the structural requirements of ICH E3 more applicable in an era of increasing disclosure. A mapping tool assigns specific report content to the sections of ICH E3.
Relationship to the Clinical Study Report
A Clinical Study Report provides a comprehensive summary of a single clinical trial, combining clinical description, statistical presentation, and their evaluation. ICH E3 describes the structure and content of such reports for therapeutic, prophylactic, or diagnostic trials, focusing primarily on efficacy and safety. CORE Reference addresses the practical interpretation of this structure when a report is prepared simultaneously for regulatory purposes and subsequent publication.
The guide was developed between 2014 and 2016. Its foundation remains the 1995 ICH E3, including subsequent Questions and Answers. Consequently, CORE Reference does not address a study’s data collection, but rather the appropriate text and table architecture used to present audited clinical data within the study report.
Manual with Mapping Tool
The E3-based mapping tool links topics and statements to the relevant sections of a study report. It can assist medical writers in placing information where it technically belongs within the report, rather than addressing it multiple times or only in appendices. This applies to study objectives, protocol deviations, efficacy analyses, safety evaluations, and the relationship between text, tables, and listings.
CORE Reference takes the disclosure of clinical documents seriously as a practical context. A report must be reviewed prior to publication because personal data or commercially confidential information may be treated differently than the scientific content. The manual does not link this subsequent usability to a reduction of the Clinical Study Report, but rather to a clear and consistent presentation of ICH E3 information.
Distinction: A Guide, Not a Template
CORE Reference is explicitly not a template to be simply filled with data for every study. It provides no pre-formulated passages and no mandatory master file that would allow the technical assessment of a study report to be automated. Its function is that of a manual: it explains decisions regarding the placement and clarity of content in relation to the ICH E3 structure.
The existing entry ‘Clinical Study Report’ refers to the regulatory report document; CORE Reference is the tool for its creation. It is also distinct from CONSORT: CONSORT is aimed at scientific manuscripts for randomized trials, whereas CORE Reference is focused on a complete Clinical Study Report according to ICH E3. Medical writing is the activity, not the specific E3-based reference work.
Furthermore, the ICH E3 structure requires an integration of clinical and statistical perspectives. For example, a report cannot speak intelligibly about efficacy if it remains unclear which population was analyzed or how protocol violations were accounted for. CORE Reference assists in connecting such sections because its mapping leads from a single detail to the locations where it must be technically categorized within the report. This is particularly useful when different specialist authors are working on separate chapters.
The utility of the tool also lies in terminology. In a complete report, terms for analysis sets, endpoints, and evaluation time points must mean the same thing across text, tables, figures, and appendices. CORE Reference does not create this consistency automatically, but it makes the E3 sections visible where contradictions would be particularly consequential. It can thus prepare the way for targeted editorial and statistical quality control.
Relevance for clinical trials
Work on the Clinical Study Report only reliably begins once the protocol, data specifications, statistical analysis plan, table and listing plan, and safety information are aligned. With an E3 report, queries often arise when textual statements do not match the analysis populations or when important context is only found in an attachment. CORE mapping can assist during the outlining phase to specifically locate such information gaps.
Full-service CROs like Mediconomics support the use of CORE Reference by creating E3-based CSR outlines, mapping source documents to report chapters, and coordinating between medical writing, biostatistics, and pharmacovigilance. During quality control, tables, narratives, and section references can be checked against the report text. For the subsequent publication of clinical data, it also allows for early identification of which passages require a data protection or confidentiality review.
Frequently Asked Questions (FAQ)
Is CORE Reference a mandatory ICH guideline?
No. The underlying ICH E3 guideline is the regulatory reference framework. CORE Reference is a tool developed by professional associations for its practical application.
Can CORE Reference replace a Clinical Study Report?
No. It is not a report document, but a guide with a mapping tool for the creation of such a report.
Why is CORE Reference relevant for published CSRs?
The clear E3-based structure facilitates the review of a report before information is prepared for public disclosure.
Regulatory References
- ICH E3 “Structure and Content of Clinical Study Reports” — The basic structure for complete clinical study reports.
- ICH E3 Questions and Answers — Clarifies interpretation questions regarding the ICH E3 guideline.
- CORE Reference Mapping Tool — Maps report content to ICH E3 sections.
- EMA Policy 0070 — Regulates the publication of certain clinical data from centralized marketing authorization procedures.