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.

BACKGROUND: CORE (Clarity and Openness in Reporting: E3-based) Reference (released May 2016 by the European Medical Writers Association [EMWA] and the American Medical Writers Association [AMWA]) is a complete and authoritative open-access user's guide to support the authoring of clinical study reports (CSRs) for current industry-standard-design interventional studies. CORE Reference is a content guidance resource and is not a CSR Template.TransCelerate Biopharma Inc., an alliance of biopharmaceutical companies, released a CSR Template in November 2018 and recognised CORE Reference as one of two principal sources used in its development. METHODS: The regulatory medical writing and statistical professionals who developed CORE Reference conducted a critical review of the TransCelerate CSR Template. We summarise our major findings and recommendations in this communication. We also re-examined and edited the Version 1 CORE Reference Terminology Table that we first published in 2016, and we present this as Version 2 in this communication. RESULTS: Our major critical review findings indicate that opportunities remain to refine the CSR Template structure and instructional text, enhance content clarity, add web links to referenced guidance documents, improve transparency to support the broad readership of CSRs, and develop supporting resources.The CORE Reference 'Terminology Table' Version 2 includes estimand as a defined term and an adaptation of the original 'worked study example' to incorporate the recently evolved concept of 'estimands'. CONCLUSIONS: As TransCelerate's CSR Template represents an important milestone in authoring CSRs, we offer CSR authors advice and recommendations on its use, similarities, and differences with CORE Reference and advise them to consider shared interpretations between the two. REGISTRATION: CORE Reference is registered with the EQUATOR Network. The TransCelerate CSR Template is not registered with any external organisation to the knowledge of the authors of this paper.

Preapproval Access and Right-to-Try Initiatives: What Are We Willing to Give Up?

There is a growing concern within the US Food and Drug Administration (FDA) and the pharmaceutical/biotechnology communities about state-based initiatives to provide access to drugs that are in the early stages of development. These legislative bills allow a patient to circumvent the protections afforded by regulated procedures as embodied in FDA regulation and guidance. Over the course of more than 80 years, the latter have served to best ensure the safety and therapeutic efficacy of new medicines and have evolved into an effective set of protections of human privacy, dignity, and fairness. To undermine these longstanding principles may have consequences which we, as society, must be prepared to address. This article examines the dynamic tensions that exist between the perceived best interests of the individual patient, the patient community, legislators, regulators, physicians, and the society at large. Decisions have consequences and, too often, these fail to be considered in the process of choosing the pathway that, in a context fraught with uncertainty, best meets a desperate need.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. REGISTRATION: CORE Reference was registered with http://www.equator-network.org on 23 March 2015.

Mythbusting Medical Writing: Goodbye, Ghosts! Hello, Help!

To meet ethical and scientific obligations, authors should submit timely, high-quality manuscripts. Authors, however, can encounter ethical (e.g., authorship designation) and practical (e.g., time and resource limitations) challenges during manuscript preparation. Could professional medical writers-not ghostwriters-help authors address these challenges? This essay summarizes evidence countering three myths that may have hindered authors from considering the use of professional medical writers. Authors with sufficient time, writing expertise, and reporting guideline knowledge may meet their obligations without writing assistance. Unfortunately, not all authors are in this position. Decisions about writing support should be based on evidence, not myths.

Time to finger point or fix? An invitation to join ongoing efforts to promote ethical authorship and other good publication practices.

In this commentary, we present evidence that unethical authorship (eg, guest and ghost authoring) and other publication practices are not restricted to the pharmaceutical industry; they also occur in academia. Such practices are not an industry problem--they are a research problem. To enhance trust in industry-sponsored research, companies have made rapid and far-reaching changes to their publication guidelines, policies, and procedures. Professional medical writers have adopted, and continue to implement, these changes. Although evidence indicates that industry practices are improving, there is certainly more to do, both in industry and academia. We invite readers to join ongoing efforts to promote ethical publication practices.

What should be done to tackle ghostwriting in the medical literature?

BACKGROUND TO THE DEBATE: Ghostwriting occurs when someone makes substantial contributions to a manuscript without attribution or disclosure. It is considered bad publication practice in the medical sciences, and some argue it is scientific misconduct. At its extreme, medical ghostwriting involves pharmaceutical companies hiring professional writers to produce papers promoting their products but hiding those contributions and instead naming academic physicians or scientists as the authors. To improve transparency, many editors' associations and journals allow professional medical writers to contribute to the writing of papers without being listed as authors provided their role is acknowledged. This debate examines how best to tackle ghostwriting in the medical literature from the perspectives of a researcher, an editor, and the professional medical writer.

International Society for Medical Publication Professionals (ISMPP) position statement: the role of the professional medical writer.

The International Society for Medical Publication Professionals (ISMPP) is an independent, nonprofit professional association with members from the pharmaceutical, medical device, and biotechnology industries; publication planning and medical communications companies; academia; and medical journal staffs, including editors and publishers. ISMPP's mission is to support the educational needs of medical publication professionals by providing a forum to facilitate awareness and development of best practices in publication planning and implementation, and fostering consensus policies related to medical publishing. This position statement reflects our concern about the current climate of mistrust regarding the use of professional medical writers in the preparation of manuscripts. We acknowledge the skills and training of medical writing professionals and support their role in working with research teams to develop clear and concise manuscripts in a timely fashion. Further, we support complete and transparent disclosure of the role of the medical writer and the source of funding for the writing initiative in order to build awareness of, and trust in, the appropriate use of medical writing professionals. ISMPP endorses use of the contributorship model, which offers detailed information on the roles of all who participated in planning, conducting, developing, and publishing medical research. Further, we propose that this model be integrated into the standard operating procedures of the diverse organizations that comprise our membership because the responsibility for authorship disclosure is shared by sponsors, authors, study investigators, and medical writers. Finally, we commend the many organizations that have worked to increase recognition and understanding of the legitimate role of the medical writer, and are eager to work in concert with them to ensure the rigorous maintenance of all ethical standards for reporting the results of medical research.

The involvement of professional medical writers in medical publications: results of a Delphi study.

OBJECTIVE: Using a Delphi Consultation process, a group of medical writers established by the European Medical Writers Association (EMWA) set out to determine the current thinking on the problems of ghostwriting in medical publications and what should be done about them. In this context, ghostwriting is where a professional medical writer prepares a manuscript on behalf of a named author, but the writer is not listed as an author. METHODS: A 4-round Delphi consultation process was conducted via email to generate statements about the main issues in ghostwriting. Participants rated their agreement with the statements on a scale of 0-10. RESULTS AND CONCLUSIONS: Members of the task force strongly believed that professional medical writers can improve the quality of scientific papers, but that fact is often not recognised outside the medical writing profession. At least in part, this is because of a perception that ghostwritten papers may have been inappropriately influenced by pharmaceutical companies. One theme that emerged strongly from the discussions was transparency. Members thought it very important that the existence of a ghostwriter should always be made clear to the reader. Another strong theme was the importance of defining in detail what practices relating to ghostwriting are ethical, and what practices are not. This definition of ethical ghostwriting should be widely known, and unethical ghostwriting should be strongly condemned. Use of the term 'ghostwriting' itself was questioned. Members of the task force felt that use of a more neutral term should be encouraged. The task force suggested various activities for ensuring that above the objectives could be met, including discussions with other interested parties, such as journal editors and pharmaceutical companies, educating medical writers about ethical practices, further research into ghostwriting, and developing guidelines for ethical medical writing.