Raising the Bar: Why Quality and Training Will Define Your Success Under ICH E6(R3)

As clinical trials become increasingly complex, trial leaders are faced with a critical challenge: how to ensure quality and compliance in an evolving regulatory landscape.

On January 6, 2025 the International Council for Harmonisation (ICH) officially adopted the E6(R3) guideline on Good Clinical Practice (GCP), marking a pivotal moment for clinical trial conduct.  Given the increasing complexity across clinical trials, this update introduces a proportionate and risk-based approach to quality management and participant safety. The guideline’s release underscores the necessity for trial leaders to implement appropriate process changes that meet the modern challenges of the emerging clinical trial environment.

The concept of proportionality and risk-based approaches raise the stakes for trial sponsors and provide new opportunities to carefully tailor and align the policies, procedures, and tools that sponsors employ to the risks each trial represents.  As stated in Section 7.1 of the guideline, “Trial processes should be proportionate to the risks inherent in the trial and the importance of the information collected.” While the guideline pushes for an overall increase in focus on quality management, patient safety, and training protocols; the level of increased rigor should match the proportional risk. 

The ICH E6(R3) Revolution: What You Need to Know

The transition from R2 to R3 represents a significant evolution in the ICH guidelines – introducing “quality-by-design” that further refines risk management and establishes clearer roles and responsibilities.  In assessing the proportional risk and resulting level of study conduct, Sponsors and CROs should focus on these key changes as they optimize clinical quality:

1. Risk-Based Quality Management:
   • Encourages proactive identification, evaluation, and mitigation of risks that impact trial outcomes.
   • Moves away from reactive monitoring to a system that focuses on critical-to-quality factors.
2. Flexibility and Adaptability:
   • Supports diverse trial designs, including decentralized and adaptive models.
   • Aligns with modern technologies like eClinical tools and real-time data analytics.
3. Participant Safety and Data Integrity:
   • Strengthens safeguards for participants while ensuring robust data quality.
4. Continuous Improvement:
   • Promotes a proactive cycle of refinement in trial design and operations.

Failure to align with these changes could mean increased costs, delays, and potential regulatory non-compliance—a risk no trial leader can afford.

The Overlooked Pillar of Quality: Training and Site Initiation

Why Training is Central to ICH E6(R3)’s Quality Focus

The new guidelines mandate a greater focus on proactive quality management and quality-by-design principles, and recognize the increased role that training must play in ensuring these critical-to-quality factors are prioritized and achieved. 

There are three key areas in ICH E6(R3) that illustrate the increased responsibility in providing more effective training:

1. In Section 2.3.2, the guideline states, “Trial-related training to persons assisting in the trial should correspond to what is necessary to enable them to fulfill their delegated trial activities that go beyond their usual training and experience.” This emphasizes the importance of delivering more effective study specific training that ensures individuals can competently perform tasks outside their usual scope of expertise, ensuring the integrity of trial operations.
2. In Section 3.4, the guideline requires that, “Sponsors must ensure that individuals involved in the trial (e.g., investigators, monitors, data managers) are appropriately trained in the use of trial systems and are qualified by education and experience to fulfill their delegated responsibilities.” This highlights the need for role-specific training that prepares personnel for their specific tasks while maintaining overall compliance with trial objectives.
3. In Section 3.10.1.3, the guideline underscores the role of training as part of broader risk management, stating, “Risk mitigation activities may be incorporated, for example, in protocol design and implementation, monitoring plans, agreements between parties defining roles and responsibilities, and training.” This positions training as a proactive measure to prevent issues and uphold trial quality.

Training impacts every stage of a trial, from protocol adherence to site readiness and data accuracy. As the guideline emphasizes, more effective and tailored training is essential to meeting the heightened quality expectations under ICH E6(R3).

Yet, traditional training methods remain outdated, leaving sites and teams underprepared.

The Hidden Weak Link in Traditional Training

Many Sponsors and CROs still rely on one-size-fits-all PowerPoint presentations delivered during Site Initiation Visits (SIVs) as their primary form of study training.  While  these generic training sessions may have “checked the box” under past industry guidelines, they fail to meet the training requirements and higher bar for quality management established under ICH E6(R3).  More critically, the limitations in the traditional training approach too often lead to:

• Protocol Deviations: Misunderstandings of complex protocols result in errors that undermine quality.
• Delayed Recruitment: Poor training on inclusion/exclusion criteria causes high screen failure rates and prolonged timelines.
• Resource Wastage: Over reliance on traditional SIVs and cookie cutter approaches to training waste valuable resources and increase the burden on already stretched study teams and sites.

The Cost of Poor Training on Quality

Ineffective training impacts critical quality metrics such as screening and enrollment rates, data accuracy, participant safety, and timely trial completion. With ICH E6(R3)’s focus on risk-based monitoring and proactive issue management, more effective and continuous training becomes essential to meeting the increased quality requirements.

What a Modern Approach to Study Training Must Deliver

To meet the quality demands of ICH E6(R3), trial leaders need to employ more modern approaches to training that go beyond traditional methods. The right approach should:

1. Simplify Protocol Complexity:
   • Break complex protocols into engaging, digestible modules that focus on critical-to-quality factors.
   • Highlight areas of confusion through predictive insights, enabling timely interventions.
2. Improve Recruitment and Retention:
   • Ensure inclusion/exclusion criteria and recruitment strategies are well understood, reducing screen failures and accelerating enrollment.
   • Offer flexible, asynchronous learning options to reduce strain on site staff.
3. Align with Risk-Based Quality Management:
   • Analyze training data to validate protocol comprehension and identify sites and personnel that may struggle to conduct the study.
   • Enable trial leaders to prioritize resources and tailor monitoring strategies proactively.
4. Facilitate Positive Behavior Change:
   • Changing behaviors to meet ICH E6(R3) standards should begin during site initiation and extend throughout the trial.
   • Select, train, validate, and activate those sites best prepared to adapt and adhere to ICH E6(R3) principles.
5. Prepare for Technological Competence:
   • With the increased use of digital tools, personnel must be trained on data governance principles and the specific technologies employed in the trial. The guideline highlights the need to “ensure personnel understand the technologies used to capture and manage data” to maintain quality and compliance.
6. Clarify Roles and Responsibilities:
   • Training must reflect clearer definitions of roles outlined in the guideline, ensuring personnel are well-equipped to execute their responsibilities. This supports the integration of “quality-by-design principles” into all stages of the trial.
   • Training must tailor content to individual study roles and nudge personnel to focus on the most critical information.
7. Enhance Operational Efficiency:
   • Reduce the time spent on Site Initiation Visits by enabling asynchronous, personalized training that maximizes the follow-on interactions with each site.
   • Equip CRAs with actionable insights from site training to focus their monitoring efforts where they are most needed.

A modern training approach under ICH E6(R3) should address these needs holistically, to achieve quality goals while proactively mitigating risks.

ArcheMedX: Delivering Quality with the Ready Platform

The ArcheMedX team has extensive experience powering a more modern approach to study training and site initiation that directly aligns with ICH E6(R3)’s quality mandates. By relying on the Ready Platform by ArcheMedX, sponsors and CROs are delivering improved trial results with a proven system that:

• Transforms Training: Rapidly converts study documents into interactive, on-demand training experiences tailored to individual roles that replace ineffective, generic sessions.
• Delivers Predictive Insights: Real-time dashboards identify risks early and inform proactive, risk-based decision-making for study leaders.
• Achieves Proven Results: Sponsors report a 90% reduction in SIV time, a 179% improvement in protocol knowledge, and enhanced compliance with 90% of sites completing assigned training in less than 3 weeks.

With Ready, sponsors can ensure their teams are equipped to meet the challenges of ICH E6(R3) and deliver high-quality, compliant trials.

Conclusion: Quality Starts with Readiness

The ICH E6(R3) guidelines are a wake-up call for clinical trial leaders. Quality can no longer be an afterthought—it must be proportionally designed into every aspect of a trial, starting with how we train and prepare our sites and study teams. The Ready platform by ArcheMedX empowers trial leaders to meet these new standards with confidence, ensuring their teams are prepared to deliver high-quality trials at lower cost.

Are you ready to transform your approach to training and quality? Contact us today to learn more about Ready or to schedule a demo.

Let’s ensure your team is Ready—because quality starts here.