Impact of the ICH E6(R3) Guideline on Medical Writing

Introduction

The third revision of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 guideline or ICH E6(R3), a cornerstone of clinical research quality, became effective on 23 July 2025 in the European Union. This revision emphasizes modernized clinical research resulting from innovations in trial design, technology, and operations, and allows for greater flexibility in trial design and conduct adapted to the specific needs of the trial (rather than a one-size-fits-all approach to clinical trials). It highlights the importance of thoughtfulness in the design and execution of the clinical trial (eg, quality by design and critical-to-quality factors) to guarantee participant safety and data reliability and to reduce burden on all parties involved.

Background

The revised guideline has undergone substantial changes in structure and content. The restructured format with core Good Clinical Practice (GCP) principles and 2 annexes (one for interventional clinical trials and one for non-traditional interventional clinical trials) aims to provide more clarity and better readability and allows to make future updates easier. Additional annexes may be developed to respond to the needs of interested parties and to address emerging innovations in trial design and conduct. Content-wise, an entirely new section on data governance was included and all existing sections were revised to account for the new trends and technological advancements in clinical research.

ICH E6(R3) emphasizes quality by design and risk-based quality management through identifying the factors (data and processes) critical to ensuring trial quality, assessing potential risks, and implementing proportionate control measures. Other key changes include a focus on patient-centricity, greater transparency, modernized data management practices, and integration of technology. Understanding the shifts introduced by ICH E6(R3) is essential to maintaining compliance and scientific integrity. For medical writers, these changes carry practical implications. Their role in developing clinical trial documentation—ranging from Protocols to Informed Consent Forms—requires compliance with the revised GCP standard.

Implications for Medical Writing

Medical writers have an important role in the development of the protocol and several other trial-related documents. They work together with other stakeholders involved in clinical research to produce clinical trial documents that are not only scientifically accurate but also meet regulatory expectations. These documents are used for the proper conduct (from planning to reporting) of the clinical trial to ensure participant safety and to generate reliable results. The revised ICH E6 guideline impacts medical writers, as key contributors to clinical trial documents, in many ways.

Some important implications for medical writing are listed below:

Interpreting GCP principles into clear, actionable content across trial documents (eg, to include all required elements as indicated in the guideline into the Informed Consent Form, to pre-specify data to be collected and the method of data collection in the Protocol).

Collaborating closely and proactively with other stakeholders at the sponsor level (such as clinicians, regulatory specialists, statisticians, data managers) to produce documents that reflect trial-specific risks and mitigations; are clear, consistent, and complete; and avoid unnecessary complexity.

Ensuring traceability (eg, how data are managed, analyzed, and reported) and documentation of important decisions made. Justifications or explanations should be clearly described within the trial documents (eg, provision of the rationale for the exclusion of any participant or particular data point from an analysis set in the Clinical Study Report).

Protecting the privacy and confidentiality of personal information of the trial participants by using proactive authoring techniques in clinical trial documents.

Obtaining the perspectives of interested parties, such as patients and their communities, patient advocacy groups and healthcare professionals to improve operational feasibility and further reduce unnecessary complexity.

Ensuring transparency with the timely trial registration in publicly accessible and recognized databases and the public posting of trial results. Communicating trial results to participants should be considered.

It is therefore important to review and update the internal documentation related to working practices for medical writing, including, but not limited to, the following:

Internal document templates: to accommodate the new content requirements as stipulated in the guideline. For example, the integration of language for remote monitoring processes within protocol templates.

Style guides: to promote the use of clear, concise, and consistent language and to reflect the terminology or definitions used in the Glossary section of the guideline. For example, ensure use of ‘participant’ instead of ‘subjects’ in all documents.

Standard Operating Procedures (SOPs) and quality management systems: to integrate the new requirements and expectations from the guideline, and to reflect changes in roles and responsibilities. Examples are SOPs for authoring and review, version control, and disclosure processes.

Work instructions or job aids: to provide specific, actionable guidance aligned with the updated procedural expectations, to adapt to new tools or workflows adopted in line with the guideline. For example, risk documentation and creation of quality control checklists for trial documents.

Training materials (or creating new ones): to educate staff on the implications of the guideline, and to promote awareness of updated regulatory language and expectations. Examples may include training in risk-based quality management and ethics.

Medical writing metrics (eg, key performance and key risk indicators): to proactively identify and manage risks to trial process quality, to include quality- and risk-related indicators in tracking documentation planning and performance, and to identify areas needing targeted training or process improvement. For example, management of a risk register.

To remain aligned with ICH E6(R3), medical writers can engage in targeted training on GCP principles outlined in the new guideline. It is also important to thoroughly understand the concepts of quality by design (which emphasizes planning for quality from the outset) and adaptive clinical trials (which allow for modifications during the trial based on accumulating data from the trial). Staying informed and up-to-date on evolutions in clinical research is essential for ensuring that individuals involved in clinical trials (such as those in medical writing) are qualified through education, training, and experience.

Conclusion

The ICH GCP E6(R3) guideline introduces significant changes for medical writers, especially in how clinical trial documentation is structured and developed. The transition to ICH E6(R3) signifies a fundamental shift in mindset from a reactive, compliance-focused approach to a proactive, risk-based, quality-driven approach. It demands greater strategic and analytical thinking from medical writers. Successful implementation of current GCP guidance requires revising documentation (such as document templates) and training materials and adapting approaches to writing with closer collaboration and broader stakeholder engagement.

If you would like to learn more about the ICH E6(R3) guideline and its impact on medical writing, please refer to our Emtex Academy training ‘ICH GCP E6(R3)’ that will be available shortly.