When introduced in 2017, ICH E6 (R2) represented the biggest change to international clinical research in 18 Years. Developed as a response to the rising complexity of studies and the Industry’s increasing reliance on electronic data management, the addendum provides core guidance for the management of clinical research. The updates incorporate a clear expectation for Risk-Based Quality Management methods, reinforcing the need for risk planning and RACT, Quality Tolerance Limits (QTLs), and Centralized Monitoring including statistical data monitoring. It also reinforces the need for documentation of Centralized Monitoring activities, and for a Sponsor’s responsibility to oversee the CRO services in managing their studies. ICH guidance is generally adopted by the major regulatory authorities such as FDA, EMA, PMDA etc.,
- The responsibility for the quality and integrity of trial data resides with the Sponsor, even if trial duties are outsourced to a Clinical Research organization (CRO).
- Quality assurance systems should focus on human subject protection and reliability of trial results.
- Sponsors should implement a quality management system to use from trial design through close out.
- Sponsors should use a risk-based approach to develop the study protocol and study materials.
- The Sponsor should perform a root cause analysis and implement and document corrective and preventative actions for any issues.
- Every study requires a monitoring plan that includes information on potential risk of harm to participants, how the study will be monitored, the monitoring plan for critical data and processes etc.,
In the spring 2018, the Food and Drug Administration (FDA) published their updated thinking on regulatory standards for clinical trials, which took form in a document produced collaboratively with the International Council for Harmonisation (ICH): E6 (R2) Good Clinical Practice: Integrated Addendum to ICH E6 (R1). This document represents the FDA’s current thinking on ethical and scientific considerations for designing, conducting, recording and reporting trials that involve human subjects.
- Sponsors should implement quality systems to manage quality throughout the trial process (design, protocol, tools, procedures, data collection, as well as the collection of info that impacts decision making)
- The quality management system should utilize a “risk-based approach” regarding critical processes and data identification, risk identification, risk evaluation, risk control, risk communication, risk review, and risk reporting.
- For the risk control aspect, FDA recommends that the Sponsor should decide which risks to reduce and/or which risks to accept, using risk reduction approached proportionate to the significance of the risks.
- Quality Tolerance Limits (QTLs) should be established and upon detecting deviations from the limits that were pre-defined, it should be evaluated to decide if action is required.
- Sponsors may choose onsite monitoring, centralized monitoring, or a combination of both.
- The guidance should be read in conjunction with other relevant ICH guidance.
- ICH E6 (R2) – sections 5.0 (Quality Management), 5.2 (CRO), and 5.18 (Monitoring)
- FDA extends CRADA with CluePoints to further explore a data-driven approach to quality oversight in clinical trials
- A Data Anomaly Tool for Site Selection at FDA [FDA-Published Poster]
- Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring
MCC is a trusted partner in the clinical trials industry—identifies what to measure and how to assess the critical components of what is changing and how the industry is responding to address the changes to make improvements. MCC continually brings new insights into the leading trends within the industry.
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ICH E6 (R2)
Created in conjunction with our peers at TUFTS Center for the Study of Drug Development, this paper provides insights on how companies are responding to ICH E6 (R2) and information on the key themes on adoption.
ICH E6 (R2)
This recorded webinar covers all of the frequently asked Questions about ICH E6 (R2), Risk-Based Study Execution (RBx) and what’s required from a people, process & technology standpoint.