Clinical Researcher—April 2025 (Volume 39, Issue 2)

RULES & REGULATIONS

Justin Scott Brathwaite, MBA; Naresh Poondla, PhD, MBA

 

 

 

The International Council for Harmonization (ICH) E6(R3) Good Clinical Practice (GCP) guideline was recently updated to enhance patient safety, optimize clinical trial efficiency, and improve data integrity within clinical research.{1,2} We believe these modifications will have a positive impact on how clinical trials are conducted by increasing participant involvement, while maintaining data integrity and compliance.

ICH E6(R3) promotes greater flexibility in trial design and execution by encouraging the adoption of adaptive and innovative methodologies that include decentralized elements, digital health technologies, and real-world data.{1} This is relevant because traditional clinical trials often place a significant burden on participants, requiring frequent site visits, extensive paperwork, and rigid schedules.

Therefore, it appears that ICH E6(R3) has moved toward more patient-centric strategies, which is a welcome development.{3} For instance, the guidelines mention the use of wearables and sensors as viable options for diversifying data sources in clinical trials.{1} This flexibility encourages research sites to adopt innovative methodologies, such as adaptive trial designs, real-world evidence collection, and remote monitoring.

Additionally, the new guideline promotes the incorporation of decentralized clinical trial (DCT) elements into study designs where applicable, allowing certain study activities to be conducted remotely. The integration of DCT elements into the guideline is important because DCTs have improved access to life-saving treatments for diverse patient populations by overcoming various logistical challenges.{4,5} We believe that the promotion of decentralized trials and digital health technologies aligns with our observations in recent years—that patients are more likely to participate in studies when trials meet their needs. By minimizing patient burden and enhancing engagement, the ICH E6(R3)’s guideline will improve retention rates and produce more reliable and generalized data.

Another essential element of ICH E6(R3) is risk-based quality management, which pushes sites to prioritize initiatives that have a real influence on data integrity and patient safety.{1} Quality management has frequently been compliance-driven, requiring a great deal of documentation and monitoring. By assessing potential risks and implementing suitable control measures, sites can streamline processes and eliminate unnecessary tasks. We believe this could lead to a more sustainable research environment, improved data quality, and a reduced likelihood of protocol deviations.

ICH E6(R3) also balances technological innovation with an increased emphasis on data governance and security by stressing the development of processes that account for data protection and integrity throughout the entire data life cycle. Examples include ensuring the confidentiality of participant data, managing computerized systems, safeguarding trial elements such as randomization and blinding, and supporting decision-making processes such as data finalization, unblinding, analysis allocation, and design changes.{1}

In response to these changes, clinical research sites must improve cybersecurity defenses, implement consistent data management procedures, and guarantee that employees receive enough training on digital compliance. We anticipate that sites may need to collaborate more closely with data management and information technology experts to meet these broader requirements.

Another important update in ICH E6(R3) is the clearer definition of roles and responsibilities within clinical trials. For instance, a clinical research manager at a nonprofit academic medical center may frequently interact with sponsors, contract research organizations, and investigators. The new guideline delineates these responsibilities more explicitly, ensuring better collaboration and accountability. This clarity is crucial in preventing misunderstandings, ensuring regulatory compliance, and optimizing trial efficiency. We speculate that sites may need to revise certain standard operating procedures (SOPs) to align with these definitions.

Overall, the implementation of ICH E6(R3) represents a positive step forward for clinical research sites. While adapting to these changes will require initial effort, the long-term benefits—enhanced trial efficiency, improved data quality, greater patient engagement, and stronger compliance—are well worth it. By leveraging the opportunities presented by ICH E6(R3), it is possible to contribute to more efficient, patient-friendly, and scientifically robust trials that ultimately benefit patients and the broader healthcare community.

References

1. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. 2025. ICH E6(R3) Good Clinical Practice: Step 4 Final Guideline. https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf
2. Bhatt A. 2023. The revamped Good Clinical Practice E6(R3) guideline: Profound changes in principles and practice! Perspectives in Clinical Research 14(4):167–71. https://doi.org/10.4103/picr.picr_184_23
3. Sharma N.S. 2015. Patient centric approach for clinical trials: Current trend and new opportunities. Perspectives in Clinical Research 6(3):134–8. https://doi.org/10.4103/2229-3485.159936
4. Girardin JL, Seixas AA. 2024. The value of decentralized clinical trials: Inclusion, accessibility, and innovation. Science 23:385(6711). doi: 10.1126/science.adq4994.
5. Brathwaite JS, Goldstein D, Dowgiallo E, Haroun L, Hogue KA, Arakaki T. 2024. Barriers to clinical trial enrollment: Focus on underrepresented populations. Clinical Researcher 38(2). https://acrpnet.org/2024/04/12/barriers-to-clinical-trial-enrollment-focus-on-underrepresented-populations

 
Justin Scott Brathwaite, MBA, is a Site Readiness and Regulatory Senior Startup Specialist with Fortrea, a contract research organization.

Naresh Poondla, PhD, MBA, is a Clinical Research Scientist at the Icahn School of Medicine at Mount Sinai.