Developing the Clarity and Openness in Reporting: E3-based (CORE) Reference user manual for creation of clinical study reports in the era of clinical trial transparency

Samina Hamilton, Aaron B. Bernstein, Graham Blakey, Vivien Fagan, Tracy Farrow, Debbie Jordan, Walther Seiler, Anna Shannon, Art Gertel, for the Budapest Working Group

Interventional clinical studies conducted in the regulated drug research environment are reported using International Council for Harmonisation (ICH) regulatory guidance documents: ICH E3 on the structure and content of clinical study reports (CSRs) published in 1995 and ICH E3 supplementary Questions & Answers (Q & A) published in 2012.Since the ICH guidance documents were published, there has been heightened awareness of the importance of disclosure of clinical study results. The use of the CSR as a key source document to fulfil emerging obligations has resulted in a re-examination of how ICH guidelines are applied in CSR preparation. The dynamic regulatory and modern drug development environments create emerging reporting challenges. Regulatory medical writing and statistical professionals developed Clarity and Openness in Reporting: E3-based (CORE) Reference over a 2-year period. Stakeholders contributing expertise included a global industry association, regulatory agency, patient advocate, academic and Principal Investigator representatives. CORE Reference should help authors navigate relevant guidelines as they create CSR content relevant for today's studies. It offers practical suggestions for developing CSRs that will require minimum redaction and modification prior to public disclosure.CORE Reference comprises a Preface, followed by the actual resource. The Preface clarifies intended use and underlying principles that inform resource utility. The Preface lists references contributing to development of the resource, which broadly fall into 'regulatory' and 'public disclosure' categories. The resource includes ICH E3 guidance text, ICH E3 Q & A 2012-derived guidance text and CORE Reference text, distinguished from one another through the use of shading. Rationale comments are used throughout for clarification purposes.A separate mapping tool comparing ICH E3 sectional structure and CORE Reference sectional structure is also provided.Together, CORE Reference and the mapping tool constitute the user manual. This publication is intended to enhance the use, understanding and dissemination of CORE Reference.The CORE Reference user manual and the associated website (http://www.core-reference.org) should improve the reporting of interventional clinical studies.Periodic updates of CORE Reference are planned to maintain its relevance. CORE Reference was registered with http://www.equator-network.org on 23 March 2015.