Risk-based quality management
Risk-based quality management (RBQM) is an end-to-end process model for continuously identifying risks throughout the lifecycle of a clinical trial. Increasing evidence shows that RBQM is one of the best ways to identify and proactively manage potential problems during a clinical study.:[1]
Overview
RBQM is a holistic approach to managing a clinical trial and is one way to address clinical trial complexity.[2] RBQM allows drug developers (also known as drug sponsors) to manage the quality of the entire clinical trial lifecycle: design, execution, evaluation, and reporting. RBQM begins at protocol design so drug developers can build in risk-mitigation strategies from the outset of the study. In addition, RBQM also helps identify changes that could improve the management, monitoring, or processes of a trial.[3]
History
RBQM is an expansion of the strategy of risk-based monitoring (RBM), which was written into U.S. and European regulatory guidance in 2013. RBM uses software to analyze trial data in real time and identify potential risks to the quality and safety of the trial. RBQM applies RBM strategies to all aspects of quality management for a clinical study.[4]
RBQM is rooted in the principles of pharmaceutical Quality by Design (QbD), a concept outlined by the International Council for Harmonisation (ICH) in 2009.[5] Pharmaceutical QbD dictates that, at the outset of drug development, developers must set clear objectives for the product. It also emphasizes the importance of using science and risk management to understand and control the drug development process.[6]
Practice
The components of RBQM are outlined in the guidance document E6(R2) Good Clinical Practice (GCP), created by ICH. This document provides a unified standard for clinical trials in the European Union, Japan, and the United States. The guidance has been accepted by both the U.S. Food and Drug Administration and European Medicines Agency, among others.[7][8]
The key components of RBQM include[9]
- Initial Cross-functional Risk Assessment—Involves multiple stakeholders and identifies critical-to-quality (critical data and critical process) risks across the entire trial lifecycle as well as mitigation strategies, which will inform project plans.
- Ongoing Cross-functional Risk Assessment—A continuous process of revisiting and adjusting the initial risk assessment and planned mitigations as the trial proceeds based on incoming data and any new developments within or outside of the trial that could affect quality.
- Quality Tolerance Limits (QTLs)—Pre-determined limits for specific trial parameters that, when reached, signal that further evaluation is needed to determine if action is warranted.
- Key Risk Indicators (KRIs)—Metrics used to assess site performance, either compared to other sites or to established values.
- Centralized Monitoring—The remote review of aggregated electronic data, including data analysis.
- Off-Site/Remote-site Monitoring—Replacement of some or all on-site monitoring visits with remote-site monitoring visits, where and when allowed by regulatory authorities. When monitoring remotely, a targeted and/or triggered review of documents and data is used.
- Reduced SDV—Shift from 100% SDV to more targeted monitoring.
- Reduced SDR—Shift from 100% SDR to more targeted monitoring.
Adoption
Regulatory agencies are encouraging the use of RBQM. Draft guidance from ICH titled E6(R3) calls for drug developers to identify factors critical to the quality of the trial in order to protect patients, trial results, and subsequent clinical decisions. The extended family of ICH efficacy guidelines is expected to be integrated with the risk-based management principles of E6 (R3).[10]
Implementation
Industry implementation and adoption of Risk Based Monitoring and RBQM has been less extensive than expected. One reason cited for the incomplete adoption and partial implementation are misconceptions that it might not fit into all studies.[9] This misconception needs further discussion as CROs like Parexel for example use a "fit-for-purpose monitoring strategy" that customizes the RBQM process based on requirements and overall complexity of the study.[10]
Other explanations for slow adoption are a hesitance on the part of trial sponsors and CROs to reduce the amount of source data review and source data validation in favor of a more targeted approach, the need for new and unfamiliar technology, and an incorrect assumption that this methodology is less likely to satisfy regulators.[9]
See also
References
- ↑ "Establishing Risk-Based Monitoring within a Quality-Based System as "Best Practice" for Clinical Studies – ACRO". Retrieved 2021-11-24.
- ↑ "Oversight Paper on RBQM – ACRO". Retrieved 2021-11-24.
- ↑ Rosenberg, Michael (2014). "Key Considerations in the Transition to Risk-Based Monitoring". Therapeutic Innovation & Regulatory Science. 48 (4): 428–435. doi:10.1177/2168479013519631. eISSN 2168-4804. ISSN 2168-4790. PMID 30235568. Unknown parameter
|s2cid=ignored (help) - ↑ "Risk-Based Clinical Trial Management: Harnessing the Transformation of RBM to RBQM". ACRP. 1 September 2020. Unknown parameter
|url-status=ignored (help) - ↑ "ICH Harmonised Tripartite Guideline Pharmaceutical Development Q8(R2)" (PDF). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. August 2009. Unknown parameter
|url-status=ignored (help) - ↑ Yu, Lawrence X (2014). "Understanding Pharmaceutical Quality by Design". The AAPS Journal. 16 (4): 771–783. doi:10.1208/s12248-014-9598-3. PMC 4070262. PMID 24854893.
- ↑ "E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance for Industry". U.S. Department of Health and Human Services Food and Drug Administration. March 2018. Unknown parameter
|url-status=ignored (help) - ↑ Kim, EunHee; Lim, Chiyeon (April 24, 2020). "Survey of Risk-Based Quality Management Status and Establishment of Operational Model in Clinical Trials". Yonsei Medical Journal. 61 (5): 423–430. doi:10.3349/ymj.2020.61.5.423. eISSN 1976-2437. ISSN 0513-5796. PMC 7214110 Check
|pmc=value (help). PMID 32390366 Check|pmid=value (help). - ↑ 9.0 9.1 9.2 Barnes, Brian; Stansbury, Nicole; Brown, Debby; Garson, Lauren; Gerard, Geoff; Piccoli, Nickolas; Jendrasek, Debra; May, Nick; Castillo, Vanesa; Adelfio, Anina; Ramirez, Nycole; McSweeney, Andrea; Berlien, Ruth; Butler, Paula Jo (July 2021). "Risk-Based Monitoring in Clinical Trials: Past, Present, and Future". Ther Innov Regul Sci. 55 (4): 899–906. doi:10.1007/s43441-021-00295-8. PMC 8082746 Check
|pmc=value (help). PMID 33914298 Check|pmid=value (help). - ↑ 10.0 10.1 "Risk-based Quality Management Services (RBQM)". www.parexel.com. Retrieved 2021-11-24.
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