Risk-Based Quality Management Update


Applied Clinical Trials

A summarization of the topics discussed at ExL’s 10th Annual Clinical Quality Oversight Forum.

ExL’s 10thAnnual Clinical Quality Oversight Forum (which occurred on October 16-18, 2019) focused on Risk-based Quality Management (RBQM) leveraging analytics, systems, and tools with a risk-based approach to demonstrate oversight and achieve ongoing inspection-readiness. In this article, we will summarize some of the topics discussed at this conference.

Disclaimer: Due to the COVID-19 crisis, many conferences have been canceled. We are going back to cover select conferences from the past that still have relevant and useful information today.

FDA inspection trends

There was a discussion on recent trends in CDER Bioresearch Monitoring (BIMO) Inspections of Clinical Investigators (CI) and Sponsors. BIMO program is a comprehensive, agency-wide program of on-site inspections and data audits, designed to monitor all aspects of the conduct and reporting of FDA-regulated research. Miah Jung, Division of Enforcement and Postmarketing Safety at CDER, cited deficiencies in protocol and records as the most common finding in CI-related deficiencies in both domestic and foreign inspections in and Official Action Indication (OAI) classifications were most commonly attributed to shortcomings in records and drug accountability in FY 2018. Jung cited weaknesses in protocol and monitoring as the most common findings in sponsor/CRO-related deficiencies in both domestic and foreign inspections in FY 2018. Even though there is no regulatory requirement for the inspected entity to respond to the FDA 483, Jung suggested providing a well-reasoned, complete, and timely 483 response within 15 working days after the completion of the inspection as it could mitigate FDA compliance decision and establish credibility.

Leveraging intelligent analytics

Steve Young, Chief Scientific Officer at CluePoints, reported that the traditional SDV process drove up to 15% of total study cost, yet only 1% of eCRF data was corrected by 100% SDV. Young indicated that centralized monitoring is a crucial component to detect operational risks, which can be assessed using statistical data monitoring (SDM), key risk indicators (KRIs), and Quality Tolerance Limits (QTLs). SDM includes relevant statistical tests such as mean, between and within patient variability, proportion, and propagation, to be executed across most or all of the clinical data. KRIs assess for pre-defined risks of interest, and it is best practice to build a standard KRI library and implement a maximum of 25 KRIs per study. QTL best practices also include establishing a standard QTL library (LTF rate, ET rate, etc.), defining a secondary or “early warning” limit, and creating a site-level KRI for each QTL parameter. Young indicated that 30% of traditional clinical operations cost is driven by site monitoring, and centralized monitoring can remove 80% of the SDV workload and provide up to 12% reduction in study cost.

Regulatory inspection readiness

Marion Mays, VP, Expert Services and Consulting at Phlexglobal, discussed leveraging TMF as an oversight tool for inspection readiness. Mays suggested developing a risk-based approach to TMF completeness by generating a risk number per document type; the risk number is made by multiplying the impact score (impact of missing documents using a 10-point scale) by the risk score (an effort to correct missing document status using a 6-point scale). Mays recommended that sponsors and CROs can work effectively with eTMFs by upfront planning of operating models (utilizing CRO and/or Sponsor eTMF), standardization of content and interoperability, alignment of processes (TMF plan, system access, document submission, query management, process for transfer, QC review), establishing metrics (quality, timeliness, completeness), and demonstrating sponsor oversight (TMF audit, TMF direct access, mock inspections, and vendor report review). When activities are outsourced to third party vendors, sponsor oversight can be demonstrated by a TMF audit trail (number of users in the system, times accessed, documents reviewed, approvals/e-signatures), meeting minutes, and correspondence throughout the trial. 


Risk-based quality management (RBQM) is at the core of study design (patient-centricity), study planning (risk mitigation planning), and study execution (centralized risk monitoring) and allows for continuous risk assessment. Study teams can leverage numerous analytical tools and systems like centralized monitoring and eTMF to demonstrate sponsor oversight and keep a continual inspection-ready state.

Don’t miss the upcoming 11th Clinical Quality Oversight Forum on October 5-7 in Philadelphia.  Click here for more details.  


Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.

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