Clinical Researcher—February 2026 (Volume 40, Issue 1)
GOOD CLINICAL PRACTICE
Henry Galio
With the September 2025 release of final guidance from the U.S. Food and Drug Administration (FDA) in support of the International Council for Harmonization’s (ICH’s) updated guideline for Good Clinical Practice (GCP), known as ICH E6(R3), the industry is taking a significant step forward to bring modern global clinical trial standards in line with the latest advances in science and technology.
The E6(R3) guideline highlights the necessity of adopting flexible, risk-based approaches that reflect the complexities of today’s research, enhance study efficiency, and improve how operational and regulatory challenges are managed. This involves encouraging sponsors and investigators to prioritize quality and risk assessments from the outset, using real-time data to inform timely decisions throughout the study.
In Europe, the European Medicines Agency (EMA) adopted E6(R3) principles and Annex 1 in December 2024, with the guideline going into effect in July 2025. To proactively address the guideline changes, companies are accelerating adoption of digital clinical platforms and hybrid study designs. These advancements in infrastructure aim to enhance transparency and compliance while safeguarding participant safety and data integrity.
The goal of E6(R3) is to drive stronger governance, continuous quality advancement, and consistent study collaboration globally. To meet the new expectations, sponsors, sites, and contract research organizations (CROs) should consider revising procedures, systems, and training programs for proactive oversight.
Redefining Oversight and Data Quality
The updated guideline addresses how teams handle quality, oversight, and collaboration for outsourced studies, moving beyond physical documents toward accepting a wider range of records. This includes electronic files, communication logs, and operational evidence. To maintain complete and transparent oversight, clinical teams are now encouraged to maintain traceable evidence across the study lifecycle—often supported by systems like electronic trial master files (eTMF) and clinical trial management systems (CTMSs) to enable traceable management of study conduct and decision-making processes.
ICH E6(R3) raises expectations that sponsors can ensure timely access to relevant records, regardless of where they are stored or who manages the system. To meet this requirement, it is essential for sponsors to establish a connected clinical infrastructure and develop strong relationships with outsourcing partners. This allows sponsors to be transparent about collaborations while monitoring and verifying data significance in real time.
E6(R3) will drive additional key changes in clinical trials, including:
Expanding proportionality toward risk-based processes. Organizations are encouraged to take a risk-based approach that matches the level of care in quality management, monitoring, documentation, and statistical oversight to how critical the data are (known as the Critical-to-Quality approach, or CtQ). CtQ helps reduce unnecessary work by focusing controls where they matter most, driving efficiency and speed in clinical trials.
Adopting ongoing risk assessment guidelines. A priority for sponsors will be keeping thorough records of decisions, reasoning, and actions related to managing the trial. The requirement increases accountability, especially when outsourcing tasks, and calls for improved planning, specialized roles, and technology.
Raising the bar for training and monitoring. E6(R3) will require that sponsors ensure that their personnel and those at CROs, sites, and service providers are trained on GCP practices, trial protocols, and roles. The regulation also increases expectations for investigators, including appropriate training documentation for staff and external partners, which is a new requirement for research sites. Documenting all training, including procedures outside standard measures of care, ensures compliance, site reputation, and integrity of data.
Adapting Oversight for Compliance
The new guidelines will drive organizations to move away from reactive supervision of study partners toward a more proactive, risk-based approach. Companies will prioritize activities based on the data and clearly define which records are essential, identify and monitor key risk and quality signals, and continuously monitor progress. Sponsors will start to work closer with CROs to align on what operational indicators will be tracked and how performance will be reviewed.
Establishing governance frameworks and cross-functional teams dedicated to preventing issues is a starting point. Appointing a sponsor oversight manager helps ensure that decisions are well documented and transparent. With these teams in place, organizations can quickly address new risks as they arise throughout the study.
Since E6(R3) calls on sponsors to take a proactive, evidence-based approach to oversight to maintain compliance and protect trial integrity, the following five key steps can help organizations meet these requirements.
- Create a risk-based study oversight plan
Pinpoint essential data and records that demand regular review, set clear intervals for review, and assign duties to team members with the right expertise. Tailor the approach to the trial’s phase, design, and risk profile, giving extra focus to sites or elements that carry higher stakes.
Align with CROs to agree on acceptable thresholds for key activities and bring them into the conversation early to align roles and data-sharing protocols, ensuring that oversight information, such as deviations, flow into your systems in real time. Round out the plan with targeted key performance indicators (KPIs) that flag potential problems and keep a log of every action taken.
- Establish study oversight governance
Assemble a cross-functional team that includes clinical operations, data management, quality assurance, and regulatory experts. Appoint dedicated sponsor roles, such as a trial operations manager, to maintain vigilance. Once in place, build a regular governance schedule to review progress, spot trends in deviations or quality signals, and update risk assessments during meetings. By documenting each discussion, the reasoning behind decisions, and follow-up actions, sponsors will be better equipped to spot and resolve problems early.
- Create and document evidence of oversight
Delegate specific tasks to members across the study team and set up regular reviews of CRO operational data, focusing especially on high-risk records. Apply the same thoroughness at the site level by tracking acknowledgments of safety letters, documentation submissions, and training completion. Keep digital records of all interactions to maintain context. Be sure to log site escalations, capture communication threads, and centralize deviation reports using validated technology to create audit-ready evidence for every review, decision, and follow-up.
- Evaluate CRO and vendor performance
Create a multidisciplinary team that includes clinical, procurement, and quality representatives to take ownership of performance management. Define clear KPIs focused on data accuracy, adherence to timelines, and compliance. Review these metrics regularly, document any gaps, and outline corrective actions. Establish ongoing feedback loops treating vendors as collaborators by promptly addressing issues, jointly developing improvement plans, and applying lessons learned to make future collaborations stronger.
- Evaluate changing clinical operating models
Analyze activities to determine which tasks should remain in-house and which can be delegated to CROs, considering your risk tolerance, costs, and efficiency goals. Focus on change management by providing hands-on training, updating procedures, and establishing clear governance. If possible, create an executive steering group for big-picture risks, and a focused transition team for day-to-day guidance. Adopt an operating model that acts as a “single source of truth,” and review technology needs to ensure current systems can support integrated oversight under this new framework.
Navigating ICH E6(R3) and the Road Ahead
With a call for broader data and greater qualitative accountability, the future is no longer just about managing a study. Anticipating risk and taking immediate corrective actions will become commonplace. The emphasis on essential records and traceability underscores the need for sponsors to adopt interoperable systems and validated anticipatory tools that provide access to critical data across all partners and platforms. This shift demands collaboration among sponsors, CROs, and trial sites to ensure accountability for study quality and participant safety.
Regularly checking the performance of vendors, their digital readiness, and data accuracy will be essential. Sponsors can lay a foundation for success with clear governance structures and trained staff and outsourced partners who have the knowledge and tools to satisfy ICH E6(R3) standards.
Henry Galio is Vice President, Veeva Clinical Strategy, and has more than 25 years of experience in the enterprise software industry, including 20 years in clinical research implementing more than 150 CTMS projects and advising more than 350 life sciences clients on how to get the most out of these systems.
