The updated ICH Good Clinical Practice (GCP) E6 R2 guidelines have issued a call to action for sponsors and CROs to implement improved, more efficient approaches to clinical trial design, conduct, oversight, recording, and reporting. The revision’s overall objective is to increase clinical trial quality and efficiency while continuing to ensure data integrity and protection of human subjects. In light of these changes, risk-based quality management has become the new standard for managing quality throughout all stages of the trial process.
Risk-Based Quality Management Defined
Risk-based quality management is a systematic process put in place to identify, assess, control, communicate, and review the risks associated with a clinical trial throughout its lifecycle. ICH E6 R2 stresses that the methods used to ensure and control trial quality should be proportionate to the risks inherent in the trial and the importance of the information collected. In addition, the sponsor should ensure that all aspects of the trial are operationally feasible and should avoid unnecessary complexity, procedures, and data collection.
Adopting a risk-based quality management approach can facilitate more informed decision-making and more efficient utilization of available resources. Ideally, the process should begin at the time of protocol design so mitigation can be built into the protocol and other trial-related documents.
Designing and Developing a Risk-Based QMS
A critical first step in designing and developing a risk-based quality management system is for sponsors to assess the current state of their QMS and then perform a gap analysis to evaluate their risk and quality needs. ICH E6 (R2) outlines a seven-step process for implementing a QMS using a risk-based approach:
- Critical Process and Data Identification. During protocol development, the sponsor should identify those processes and data that are critical to ensuring protection of human subjects and the reliability of trial results.
- Risk Identification. The sponsor should identify risks to critical trial processes and data. Risk needs to be considered at the system level (e.g., standard operating procedures, computerized systems, personnel) and the trial level (e.g., trial design, data collection, the informed consent process).
- Risk Evaluation. Risk evaluation is a three-step process that starts with assessing the likelihood of errors occurring given the existing risk controls. The second step involves the extent to which such errors would be detectable. The last step is an assessment of the impact of such errors on human subjects and on data integrity.
- Risk Control and Mitigation. The sponsor must decide which risks to reduce and which to accept. Importantly, the approach used to reduce risk to an acceptable level should be proportionate to the significance of the risk. Risk reduction activities may be incorporated into protocol design and implementation, monitoring plans, agreements between parties, and training. Predefined quality tolerance limits should be established, and detection of deviations from these limits should trigger an evaluation to determine whether action is required.
- Risk Communication. It is important for the sponsor to document quality management activities. The sponsor should communicate quality management activities to those who are involved in or affected by such activities to facilitate risk review and continuous improvement during clinical trial execution.
- Risk Review. Risk review is not a static event. The sponsor should periodically review risk control measures to ensure that they remain effective and relevant, taking into consideration emerging knowledge and experience.
- Risk Reporting. The sponsor should describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the study report.
The process of designing, developing, and implementing a risk-based QMS may seem time-consuming and overwhelming, but adopting a comprehensive risk-based monitoring technology may help ease the transition.
 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice. Available at www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf.