Meeting Background:

Current models for clinical trial design, implementation and oversight may have become outmoded and unsustainable in a global, complex clinical trial environment. In particular, existing oversight models, which generally rely on frequent, on-site monitoring visits by sponsor personnel, may not optimally address the most critical risks to trial integrity. A key conclusion of the Clinical Trials Transformation Initiative (CTTI) Monitoring Project was that clinical trial monitoring should be viewed as one component of an overall quality framework. Project participants, representing a broad cross-section of the clinical trials enterprise, agreed that widespread adoption of an enlightened “Quality by Design” approach to trial planning, conduct, and oversight is needed to ensure trial quality and efficiency. Such an approach would apply risk management principles to the design and execution of clinical trials.

Quality by Design (QbD) emphasizes building quality into a process from the beginning and has been successfully applied in the manufacturing arena. Applied in clinical development, this approach would prospectively examine the design and objectives of trial and identify “critical to quality” factors (e.g. key data and trial processes such as randomization). Understanding what aspects of a trial are “critical to quality” is essential to subsequently identifying and managing important and likely risks to trial quality. These risks can be managed through modifying trial design, tailoring its implementation, and providing sensible, risk-based oversight.

Participants in an inaugural CTTI workshop on “Quality Risk Management: Making Clinical Trials Fit for Purpose” held in August 2011 explored principles of risk management and Quality by Design from other disciplines and examined how such principles could be adapted to enhance clinical trial design and execution. Participants generally agreed that these approaches have the potential to improve clinical trial efficiency while enabling sponsors and clinical investigators to meet their fundamental obligations to protect individuals who volunteer for research and to oversee their trials. In particular, these approaches reposition monitoring as one tool for ongoing evaluation and improvement. Focusing on critical aspects of a trial could also substantially reduce the burden of clinical trial conduct by relieving sponsors of a perceived obligation to mitigate every potential risk posed by a trial, especially for those activities that minimally affect data quality and human subject protection.

Meeting Objectives:

• Develop understanding of risk-based Quality by Design for clinical trials of drug treatments, from general principles, real-world examples, and hypothetical case studies
• Gain confidence in the application of such concepts to clinical trials
• Identify obstacles to the adoption of this approach
• Identify opportunities for dissemination of these principles and practices to a broad array of stakeholders.