Navigating Digital Transformation in Clinical Research: Leveraging ICH E6 (R3) Guidelines for Success

Clinical research is in a state of evolution, with organizations forced to respond to market pressures while simultaneously adapting to an increasingly digital environment. These pressures include a rise in R&D costs, healthcare consumerism, patient centricity, and a decline in the appearance of blockbuster-status products. 

The impact of these pressures has varied among organizations. As a result, organizations are at different stages in their digital transformation journeys. To provide more universal structure, the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) recently released a new draft guideline for Good Clinical Practice (GCP). 

The new revision, ICH E6 (R3), intends to modernize, harmonize, and adapt existing GCP guidelines to support the latest innovations in clinical trials.

Incorporating technology with the aid of ICH E6 (R3) guidelines can provide significant benefits to research organizations and study trials, including increased study safety, patient centricity, participant diversity, data integrity, transparency, and overall efficiency. 

What should life sciences organizations be focused on?  

While ICH E6 (R3) includes an abundance of recommendations across a wide range of topics, we’re digging into guidelines that we believe can be most impactful for improving clinical trials through the incorporation of digital practices, including: 

• Guidelines for risk-based trial design 
• Guidelines for use of digital technology in clinical trials 
• Guidelines for increasing flexibility in trial design 
• Guidelines for increasing flexibility in informed consent  

I. Digital-forward risk-based trial design 

In response to FDA and ICH directives, the life sciences sector is embracing a risk-based approach to trial design enabled by digital tools and analytics. This approach proactively identifies and mitigates key quality risks, defined as any factor that poses a threat to the safety, integrity, and compliance of the people and processes in a trial.

II. Integrating digital technology into clinical trials 

ICH E6 (R3) provides guidelines on incorporating cutting-edge digital technologies and diverse data sources into clinical trial design and execution—including the use of wearables and the adoption of a Quality Management System. This highlights the need for strict data protection and confidentiality requirements to accompany an innovative, digital transformation. 

III. Flexible trial design for innovation 

ICH E6 (R3) provides guidelines for increasing flexibility in clinical trial designs to drive more innovation. This includes a shift from a process-based to a principles-based design that empowers investigators to adapt the guidelines to their specific circumstances and ensure trial outcomes align with patient population needs.

IV. Informed consent flexibility

These guidelines introduce the possibility of remote/electronic informed consent. This new approach allows for flexible methods of sharing trial information with patients—including varied digital formats—while still ensuring a comprehensive understanding for participants.

What does this mean for life sciences: Deployment 

The rapid shifts in the industry’s typical operating models and technological landscape pose challenges in assimilating to new standards, protocols, and regulatory frameworks. For successful clinical trials in this environment, companies should focus on the key changes in ICH E6 (R3) and construct a clear roadmap to apply to their trials.

Considerations when implementing a risk-based clinical trials

Adopting a risk-based quality approach involves substantial upfront efforts, including document revision, trial protocol refinement, and personnel training—alongside a transformation of tech infrastructure toward digital solutions. These efforts may result in significant organizational change management while contributing to ongoing trial success. 

When shifting toward a risk-based approach, consider having open discussions on quality and risk management during the pre-trial phase to guide protocol development with built-in mitigations and iterations. Additionally, consider utilizing digital tools throughout the trial to ensure consistent oversight, risk monitoring, and analysis. The data captured by powerful digital tools such as machine learning can inform risk evaluation, improve data analysis, enable efficient trial execution, and increase automation.  

Digital solutions for risk management such as risk assessment software, electronic data capture systems, and data analytics have capacity to enhance risk evaluation data quality, trial efficiency, and product time-to-market. This approach can also optimize document and data collection by focusing on and recording key risks. 

Considerations regarding flexible, patient-centric clinical trials  

ICH E6 (R3) details methodologies to increase trial flexibility and accessibility that include digital technology adoption, patient-centric considerations, and remote informed consent. These recommendations may allow for a more efficient clinical trial process and a more diverse patient population. Increasing clinical trial efficiency, diversifying patient populations, and instituting more patient-focused trial objectives should result in more accurate trials with better patient outcomes. 

Incorporating new technology into clinical trials may result in new costs required to build the infrastructure needed for successful implementation. Organizations should consider how to account for the costs associated with additional investments in new hardware such as tablets and wearables, and new software such as e-consent platforms and cloud storage. 

Adopting a patient-centric clinical trial design approach may require the use of digital technology to collect and track data during patient recruitment to ensure all criteria are met. This approach will also require the use of digital technology throughout trials to record data in a safe and efficient manner. When integrating new technology during the study design phase, teams should consider how the data is collected and who has access to it. 

Finally, while remote informed consent can increase trial flexibility and accessibility, there may need to be considerations around communication methods and data transfers such as: 

• Using clear and concise language where possible for all aspects of trial design and informed consent 
• Providing multiple digital formats to share trial information 
• Incorporating a method to collect digital signatures; digital formats such as text, images, and video conferencing can help increase patient retention, broaden enrollment, and expand diversity in clinical trials. Additionally, the digital infrastructure needed to securely transfer and store consent data must be installed to protect PHI and maintain patient trust. 

What does this mean for life sciences: Implementation 

While ICH principles provide a comprehensive overview of best practices in clinical trials, the key challenge lies in discerning and prioritizing tactical next steps, especially considering the ongoing implementation of many of these changes. We recommend evaluating your organization's current state to highlight achieved progress, identify prevailing pain points, and outline actionable measures to propel towards enhanced operational efficiency. The ensuing framework can serve as a valuable guide to aid in your evaluation. 

What can your life sciences company do to implement digitally focused risk-based clinical trials?  

• Familiarize yourself with industry standards and regulations. 
• Form a dedicated team to strategize and oversee trial-wide risk and change management. 
• Conduct a comprehensive risk assessment, identify high-risk areas, document key findings, and implement necessary mitigation measures. 
• Develop, update, and train trial staff on Standard Operating Procedures that include incident reporting, communication expectations, and process change notifications. 
• Develop a quality and regulatory technology ecosystem:  
  
  • Assess your organization’s requirements and determine which systems are needed (i.e., CTMS, eTMF, eQMS, EDC, RTSM). 
  • Set process parameters and quality tolerance limits.
  • Document key quality factors in one centralized location, ensuring trials maintain the standards set by the trial protocol and regulatory bodies with greater efficiency and accuracy. 

What can your life science company do to increase flexibility in trial design, expand use of digital technologies, and shift toward a more patient-centric environment?  

• Initiate a technology gap analysis to determine what additional digital tools you may need to meet your organization-specific goals. Review your current infrastructure and identify answers to the following:
  • How will new technology integrate into your current system? 
  • How will you ensure data privacy when implementing new technology? 
  • Who are your current data/technology experts, and will you need to hire new experts to assist in the transition?
  • Will you need to invest in complimentary technology, hardware, or software?
• Define your target study population, including disease state specifications, demographics, and geographic limitations, prior to introducing new technology.  
• Create a patient journey map that documents the clinical journey for your target population to understand patient needs before designing trials. Journey maps should seek to:
  
  • Understand how patients identify, access, and participate in each stage of a trial. 
  • Highlight patient pain points, healthcare provider interaction points, and digital touchpoints. 
  • Inform decisions on site selection, patient recruitment methods, trial end points, outcomes, and overall design.
  • Decrease trial burden on patients, mitigate costs, improve patient retention, and assure that new digital technologies will be helpful for participants. 
• Train study coordinators to provide clear and consistent explanations of newly introduced technology to trial participants to maximize patient trust.
• Review and consider updating current funding sources and allocation strategies to account for the increased investments associated with new digital technologies. 
• Ensure implementation of digital technology complies with existing regulations.

Conclusion 

The adoption of digital practices in clinical research, guided by ICH E6 (R3), presents a pivotal opportunity for the life sciences industry. Embracing risk-based trial design and fostering flexibility are essential steps toward enhancing the quality of clinical trials. As your organization navigates this evolving landscape, it is imperative to engage in comprehensive assessments and prioritize patient-centricity to position your organization for success in an increasingly digital era of clinical research.