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CORE Reference for ICH E3 Clinical Study Report Authoring: Evolving with the Times

July 13, 2017 | Ilana Dew, PhD, Senior Clinical Research Scientist | Medical Writing Services

You may be a seasoned regulatory medical writer who has authored dozens of Clinical Study Reports (CSRs) and can recite the contents of the 1995 International Council for Harmonisation (ICH) E3 Guideline on the structure and content of CSRs with your eyes closed.

Or, you may be new to the profession. You’ve seen our blog series on getting started in the field, you have accepted a position in regulatory medical writing, and came here looking for some direction on how to interpret the ICH E3 recommendations and put together your first CSR.

Whether you fall into the former description, the latter, or anywhere in between, there’s something new that you are going to want to see.

It’s the Clarity and Openness in Reporting: E3-based (CORE) Reference user manual, created to guide authors toward best practices for creating CSRs with new clinical trial transparency and disclosure regulations in mind.

Let’s deconstruct that last part: best practices for creating CSRs with new clinical trial transparency and disclosure regulations.

Some background: two unmet needs – consistency and transparency

For over 20 years, the ICH E3 guideline has undoubtedly been the primary resource for medical writers and other regulatory professionals for how to prepare CSRs. Also widely used is the supplementary ICH E3 Questions & Answers document issued in 2012, which offers some clarification on the original ICH E3 intentions.

Those of us familiar with ICH E3 are well aware that some aspects of the guideline are ambiguous. And intentionally so, as it allows for flexibility to customize the reporting of data to the needs of an individual study or program. While this ambiguity may have been intentional and even critical, a consequence of this ambiguity has been a lack of consistency in clinical trial data reporting across authors and sponsors over time.

As regulatory medical writers, we have long needed something to move us toward greater consistency and clarity in reporting. Clear and consistent reporting of data benefits the regulatory review process and, ultimately, benefits patients.

Separate from a drive toward increased consistency in reporting, there has been a strong push toward increased transparency in clinical trial data reporting.

It’s pretty easy to list the ways that the modern drug development environment has changed since 1995 when ICH E3 was conceptualized.

With globalization, the conversion to electronic data capture and review, and platforms such as clinicaltrials.gov in which clinical trial data are shared, the need for responsible data reporting has become paramount.


Image courtesy of cooldesign at FreeDigitalPhotos.net

One of the most noteworthy steps within this global push toward clinical trial transparency and disclosure was the European Medicines Agency (EMA)’s issuing of Policy 0070, Publication of Clinical Data for Medicinal Products for Human Use, which came into effect in 2015. This recent policy mandates that all clinical trial data submitted to the EMA in a marketing authorization application, including CSRs for individual studies, must be publicly disclosed.

What does “public disclosure” mean for how we author CSRs?

  • The primary concern is patient privacy and the protection of personal data as a fundamental right of clinical trial subjects.
  • A second concern is protecting the privacy of proprietary interests or commercially confidential information.

Make way for the CORE Reference user manual

The CORE Reference is an open-access 100+ page user manual intended to guide medical writers and other regulatory professionals through the ICH E3 guidelines and support CSR authoring.

The CORE Reference was developed by regulatory medical writers and statistical professionals, with contributing expertise from stakeholders from Health Canada, Drug Information Association (DIA) Medical Writing Community’s CORE Review Task Force, a patient advocate, and an academic and Principal Investigator representative.

CORE gets its name from the following principles:

  • Clarity
  • Openness
  • Reporting: E3-based

The CORE Reference presents suggestions and best practices for creating ICH-compliant CSRs, suggesting content based on the vast experience of its developers.

Meeting two needs in a single report

The CORE Reference steers authors toward the development of a single report that satisfies needs of both:

(1) a CSR’s primary use, as a technical document for scientific and regulatory review; and

(2) its secondary use, as a document for public disclosure with sensitive information redacted.

The authors of the CORE Reference developed an incredibly thorough resource that includes the following features:

  • Insight into key terminology choices. Have you ever debated whether to use subject vs patient, or trial vs study? Investigational product, study medication, study treatment, or study drug? The CORE Reference includes background on each of these choices that may guide you toward the most appropriate selection for an individual report.
  • An ICH E3 mapping tool, which maps the CORE Reference’s suggested headings to ICH E3. Note that all CORE Reference suggested headings match ICH E3 for Level 1.
  • An annotated ICH E3 CSR with detailed and thoughtful commentary, including suggestions for text or sections that will likely require redaction prior to public disclosure.
  • A compilation of helpful resources for CSR-related reporting.

What makes the CORE Reference user manual particularly useful is that it facilitates proactive compliance with new clinical trial disclosure regulations and, moreover, offers anonymization techniques that can be built into initial authoring practices, in turn minimizing time-consuming, costly, and complex redaction efforts on the back end.

Those of us who chose regulatory medical writing as a profession probably knew from the earliest stages of our careers that the ability to adapt flexibly to changing needs or priorities – be they regulatory or project-based – is a key skill for success. With this need in mind, the CORE Reference is a fantastic tool to help evolve CSR authoring strategies to meet modern needs.

Of course, it is always advisable to consult with your team before using the CORE Reference user manual to determine whether it is the preferred approach for your project.

Further Resources

For more on the CORE Reference user manual, I recommend reading the CORE launch publication:

Hamilton S, Bernstein AB, Blakey G, Fagan V, Farrow T, Jordan D, Seiler W, Shannon A, Gertel A, and for the Budapest Working Group. Developing the Clarity and Openness in Reporting: E3-based (CORE) Reference user manual for creation of clinical study reports in the era of clinical trials transparency. Res Integr Peer Rev. 2016;1(4).

For more on the EMA’s decision toward public disclosure, I recommend reading:

Eichler H-G, Abadie E, Breckenridge A, Leufkens H, Rasi G. Open Clinical Trial Data for All? A View from Regulators. PLoS Med. 2012;9(4): e1001202.

Need Help?

IMPACT is a CRO whose team has expertise in medical writing, regulatory operations, regulatory affairs, early phase clinical trial management, and drug development consulting. We have years of experience authoring CSRs, and are prepared to evolve alongside changing regulations and their drive toward responsible reporting.

If you’d like to learn more about IMPACT and the services we provide, or if you need help writing CSRs, don’t hesitate to contact us! We’d also love it if you follow us on LinkedIn and Twitter.

Category: Medical Writing Services
Keywords: Clinical Study Report; CORE Reference; Clinical trial transparency; Clinical trial disclosure; EMA Publication Policy 0070; ICH E3; CSR

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