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

Abstract

BackgroundInterventional 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.MethodsRegulatory 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.ResultsCORE 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.ConclusionsThis 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.RegistrationCORE Reference was registered with http://www.equator-network.org on 23 March 2015.

Clinical study reports: A snapshot for aspiring medical writers

“…As per Article 37 of the EU CTR, sponsors who have had their MAAs approved are required to submit a full CSR to the CTIS within 30 days after the marketing authorisation approval. 9,16 Article 37(4) also requires the sponsor to submit a summary of the clinical trial results to the CTIS, irrespective of the outcome of the clinical trial, within one year from the end of the trial in adults (6 months for a clinical trial in the paediatric population), in all the EU languages in which the study was conducted. 9,17 Sponsors are required to provide a summary of results and a lay summary after the end of each clinical trial in the EU.…”

“…depending on the specific requirements of the regulatory authority to which it is being submitted. Medical writers use the ICH E3 template,3 the TransCelerate template,6 and the CORE (Clarity and Openness in Reporting: E3-based) Refer ence to create CSRs that are compliant with regulatory guidelines [7][8][9][10]. A CSR typically includes the following components: l Synopsis: A brief overview of the main findings and con clusions of the study l Introduction: Background in formation about the medicinal product being studied, including its intended use and the rationale for the study l Methods: The study design, objectives and endpoints, patient population, interventions, and outcomes; includes informa tion about the ethical con siderations and any statistical analyses that were performed l Results: The findings of the study, including both numeri cal data and descriptive infor mation; also includes tables, figures, and other visual aids to illustrate the results l Discussion:…”

Research Integrity and Peer Review—past highlights and future directions

“…Within the reporting section of the journal, initiatives that aim to increase the transparency and reproducibility of research have been published. These include research on standards of reporting [ 21 ] including how to correctly identify the most relevant reporting guidelines [ 22 ] and how to ensure they are up to date [ 23 ]. Of particular importance is the recognition that accurate reporting of sex and gender is key for research across multiple disciplines [ 24 , 25 ], and the guidelines have been endorsed by EQUATOR [ 26 ].…”

Critical review of the TransCelerate Template for clinical study reports (CSRs) and publication of Version 2 of the CORE Reference (Clarity and Openness in Reporting: E3-based) Terminology Table

“…Developed by the Budapest Working Group (BWG), comprising European Medical Writers Association (EMWA) and American Medical Writers Association (AMWA) members in a 2-year pro bono effort, CORE (Clarity and Openness in Reporting: E3-based) Reference [1] published in May 2016, and registered with the Equator Network [2], is a complete and authoritative openaccess user's guide to support the authoring of CSRs for interventional studies [3]. It is complete because it includes all the necessary guidance components for reporting complex modern-design clinical studies, whilst maximising both personal data protections and data utility.…”