The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has finalized the ICH GCP Guidelines ICH E6(R3). The ICH reflection paper states the “goal [of this guidance] is to provide updated guidance that is both appropriate and flexible enough to address the increasing diversity of clinical trial designs and data sources that are being employed to support regulatory and other health policy decisions”. Based on previous experience (e.g., ICH E8(R1), ICH E6(R2)), it is expected that key stakeholders of clinical trials will face challenges in operationalizing some of the requirements in the guidelines.
To address these challenges, this initiative is developing solutions that aid in understanding difficult to operationalize aspects of the guidelines. The approach is to deliver solutions developed through collaboration and stakeholder engagement across six focus areas of ICH E6(R3) outlined below. Of the six areas, TransCelerate is partnering with the Association of Clinical Research Organizations (ACRO) to co-develop solutions within two focus areas: risk management and data governance.
Navigating ICH E6(R3): Tools & Resources for Understanding Changes and Supporting Adoption (Webinar)
This webinar, held on March 4th, 2025, discusses TransCelerate’s new tools and resources for understanding the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6(R3) revision and its implementation. These tools are designed to help the industry adopt the latest good clinical practice (GCP) guidance, focusing on key areas of change including data governance, risk-based quality management, stakeholder collaboration, risk proportionality, and more. See presentation content here.
Trial Design
Focus Area Overview and Objective
TransCelerate has created a “Trial Design Toolkit” aimed at facilitating the industry’s implementation of ‘quality by design’ in the early stages of clinical trial design. This toolkit addresses the updates from ICH E6(R2) to E6(R3), guided by the principles of ICH E8(R1). It includes a variety of resources, such as a detailed comparison between ICH E6(R2) and E6(R3) with an emphasis on trial design, a visual starter kit for trial design that incorporates insights from both guidelines, a methodology for critical analysis, and a collection of case studies and practical examples related to trial design.
This toolkit may act as an aid when reviewing essential factors and procedures to be considered in the planning and ongoing oversight of a clinical trial’s lifecycle. Moreover, it underscores ICH’s call for a systematic approach to critical thinking and its integration at both the commencement and conclusion of a trial.
Trial Design Use Case Scenarios when Considering New GCP Guidelines
This case study and use case scenario deliverable consists of three sections, which are 1) use cases related to proactive trial design, 2) use cases related to reactive trial design, and 3) a critical thinking exercise. The objective of this deliverable is to demonstrate ICH E6(R3) concepts in trial design and encourage thoughtful consideration and planning to design fit-for-purpose clinical trials that are scientifically sound for their intended purpose.
Risk Proportionality
Focus Area Overview and Objective
TransCelerate has created this framework to support the understanding of a risk-based and proportionate approach to a clinical trial. Adopting a proportionate, risk-based approach in clinical trials, as encouraged by ICH E6(R3), offers several key benefits. By tailoring the level of oversight and resources to the specific risks of the trial, efforts may be focused where they are most needed, reducing unnecessary burdens. A proportionate approach helps maintain high standards of participant safety and data integrity by identifying and managing critical-to-quality factors throughout the trial. Moreover, it allows for more adaptable and innovative trial designs, accommodating diverse types of trials, including decentralized and pragmatic trials.
Deliverables
Risk Proportionality Framework
An interactive PowerPoint that provides examples of critical to quality factors and potential elements of a proportionate, risk-based approach as outlined in ICH E6(R3). This framework will support industry in understanding a risk-based and proportionate approach in the conduct of a clinical trial encouraged by ICH.
Risk Management
Focus Area Overview and Objective
TransCelerate has been working with ACRO to co-develop a “Risk Management Toolkit”, which is designed to facilitate the industry’s comprehension and application of changes in risk management, particularly with the transition from ICH E6(R2) to E6(R3). It will provide a suite of resources, including delivered solutions, such as a comparison of ICH E6(R2) and E6(R3) and control strategy considerations, and forthcoming deliverables, such as an anticipated quality management solution. The toolkit will serve as a guide to identify opportunities and challenges, highlight critical changes, and integrate risk management within the framework of ICH E8(R1) principles, such as quality by design and fit-for-purpose. TransCelerate’s work with ACRO supports the industry’s ongoing commitment to the core principles of Good Clinical Practice (GCP) by evolving existing tools and solutions, addressing known areas of improvement, and offering in-depth information for thoughtful consideration during the adoption of ICH E6(R3).
Deliverables
Acceptable Ranges for Clinical Trials: Insights from ICH E6(R3) (Co-developed with ACRO)
A considerations tool, co-developed by TransCelerate and ACRO, to support a company’s internal development and implementation of acceptable ranges under the ICH E6(R3) guideline. The tool dives into the introduction of acceptable ranges and comparison to E6(R2), implementation, and potential use case.
Key Risk Management Changes in Good Clinical Practice [ICH E6(R3)] – Infographic (Co-developed with ACRO)
An infographic that highlights key changes to the risk management elements within Good Clinical Practice Version 2 and 3. Co-developed with ACRO, this infographic aims to allow industry to easily identify the impact to their process and how to react for efficient ICH E6(R3) implementation. Based on Version 3 (draft dated 19 May 2023).
Control Strategies and Good Clinical Practice (ICH E6(R3)) (Co-developed with ACRO)
A considerations tool, co-developed with ACRO, to support the implementation of control strategies under ICH E6(R3) guideline. Application of ICH E6(R3), specifically control strategies in clinical trials, ensure protection of the rights, safety, and well-being of participants and enhance the reliability of study results. Based on Version 3 (draft dated 19 May 2023).
Data Governance
Focus Area Overview and Objective
Data governance is a new section in the ICH E6 guidelines. This section provides guidance for investigators and sponsors on managing data integrity, traceability, and security. It seeks to improve accurate reporting, verification, and interpretation of clinical trial information, complementing the responsibilities outlined in sections 2 and 3, as well as ICH E8(R1), ICH E9, and ICH E9(R1).
To support this new section and uphold ICH principles, TransCelerate and the Association of Clinical Research Organizations (“ACRO”) have co-developed adoption tools, frameworks and templates designed to support GCP stakeholders with compliance, data quality, and decision-making as well as designing fit for purpose systems and processes that meet the evolving clinical research landscape.
Deliverables
Data Governance Framework (Co-developed with ACRO)
The Data Governance framework provides a sample definition of data governance and introduces and connects the other TransCelerate/ACRO data governance solutions to help GCP stakeholders develop a data governance framework.
Data Flow Template (Co-developed with ACRO)
A template to help companies map out relevant data flows between various data collection tools (e.g., EDC, ePRO, eCOA, Central labs) and involved stakeholders (e.g., sponsor, CRO, third-party vendors) in a study. The objective of the tool is to increase clarity and coordination among all parties involved.
Safeguarding Blinding Considerations Tool (Co-developed with ACRO)
The objective of this tool is to explain the concept of safeguarding blinding in clinical research. The document covers topics such as what blinded data is, why data is blinded, the importance of maintaining blinding, who may be unblinded, and the steps to take in case of unblinding.
Technology Framework (Co-developed with ACRO)
This framework explains the computerized systems (CS) requirements outlined in ICH E6(R3). It covers potential procedures for using CS, training, security, validation, periodic reviews, system failure, technical support, and user management. It also includes TransCelerate and ACRO’s proposed definitions and outlines the potential roles and responsibilities of those involved in the process.
Data Matrix Template (Co-developed with ACRO)
A template that can help companies outline their study data provenance and collection methods, data transformation, review techniques and frequency (including references to functional plans where reviews are fully described), and data analysis. It helps facilitate the application of ICH E6(R3) requirements for data governance by providing a template to help stakeholders develop clear and structured approaches to managing study data.
Data Lifecycle Framework
Coming soon.
Monitoring
Focus Area Overview and Objective
TransCelerate has created a set of solutions that aims to support the industry in implementing monitoring strategies that are proportionate to the risk of the clinical trial. These solutions reflect both ICH E8(R1) and ICH E6(R3) guidance approaches that monitoring is a key quality control activity and should not be seen as a one size fits all trial approach.
Deliverables
The monitoring toolkit reflects the following principles of ICH E8(R1) and ICH E6(R3) guidance, 1) the extent and nature of trial monitoring should be tailored to the specific trial design and objectives and the need to ensure participants’ safety and data reliability, and 2) the monitoring strategy should be customized to include a broad range of activities and technology. The document aids sponsors in developing a monitoring strategy that is both flexible and responsive to changes identified through continuous risk reassessments.
Template for Documenting Monitoring Approach
The ‘Template for Documenting Monitoring Approach’ provides a customizable template for documenting the monitoring approaches that a company defines for a trial, based on a risk-based approach. This template will support the development of monitoring strategies based on the ICH principles.
Investigators
Focus Area Overview and Objective
ICH E6(R3) Annex I Section II focuses on the responsibilities and expectations of Investigators in clinical trials. Annex I Section II emphasizes the critical role of Investigators in ensuring the integrity, safety, and ethical conduct of clinical trials. TransCelerate developed a tool to provide support to sponsors, sites, and other interested parties to understand the changes in responsibilities outlined in ICH E6(R3), compared to ICH E6(R2).
Deliverables
GCP Summary of Changes Relating to Investigational Sites
A Microsoft Excel-based tool that provides a summary of changes comparing updates to investigator roles and responsibilities from Good Clinical Practice Version 2 to 3. The document allows interested parties to explore changes to different topics relating to investigators as well as understanding if section changes are new or updated guidance.