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TransCelerates work on their clinical trial Quality Management Systems (QMS) initiative began about one year ago. This article summarizes findings from a recent DIA publication about the initiative and evaluates potential issues during QMS framework implementation.
About a year ago, TransCelerate began working on a clinical trial Quality Management Systems (QMS) initiative, and Applied Clinical Trials interviewed Merck’s Deborah Driscoll to discuss the details of the initiative. TransCelerate recently published a few articles in the Therapeutic Innovation & Regulatory Science journal (DIA), with one publication specifically focusing on issues management in quality management systems. In this Applied Clinical Trials article, we will summarize our interpretation of the findings from the DIA publication, and analyze the publication, and evaluate potential issues during QMS framework implementation. Issues Management Programs and Triage According to the authors, good QMSs define Key Risk and Performance Indicators (KPIs/KRIs), established documentation systems based on risk levels that are based on data, proper notification systems and plans, corrective and preventative action (CAPA) initiation and resolution capabilities, and analytics to track improvements in the QMS1. The authors introduced another concept that seems to expand on TransCelerate’s definition of critical data: triaging ‘issues that matter’ (i.e., problems that impact data integrity, patient rights and safety, confidence in ethical clinical trial conduct, and regulatory requirements1). By filtering issues that matter from issues that don’t, sponsors can enhance and optimize resource utilization and allocation during clinical program administration. Moreover, this model allows managers to quantify studies that exhibit high levels of risk based on issue category frequencies. Root cause analysis and CAPAs Another directive introduced in the publication involves pinpointing the issue, and preventing reoccurrence. Study teams must conduct a thorough root cause analysis, which requires setting proper documentation and impact analysis procedures on patient safety and data integrity assessments, and exercising investigative analysis to uncover other areas of impact. The authors argue that while the intention of CAPAs are to eliminate issues that matter, the activity is insufficient without a ‘CAPA effectiveness check1,’ which basically ensures CAPA resolution and measuring its impact on eliminating issues that matter. Clinical IT systems and analytics Another concept introduced in the article involves the ability to incorporate clinical IT systems to enhance QMS oversight. For example, incorporating the planning, and execution of the QMS through technology-based workflows and forms allow management to collect data, generate visualizations to better pinpoint the types of issues that arise, and evaluate the effectiveness of the QMS over time. Additionally, the incorporation of workflows through clinical IT systems empower management to assign stakeholders, which allows for accountability, bottleneck identification, and stakeholder performance assessments1. Assessing the methodology The authors write that TransCelerate is developing tools to support the above process. Further clarifications of the process are certainly needed. For instance, the publication does not give any definitions on how to perform the triage on the basis of objective criteria and not subjective assessments. Moreover, the term ‘materially impact’ needs a clear definition. The three examples provided on Page 2 of the publication are all severe, however, they are not comparable in their nature: to elaborate, in two cases, a grave mistake has already been made (informed consent issue, and the changes in the database) whereas in the other example, there have not been any negative consequences for patients and data, even though not sending the Serious Unexpected Adverse Reactions (SUSARs) to the sites is a grave mistake. In addition, to standardize the Root Cause Analysis and the use of Clinical IT in issues management processes, more details about the processes need to be provided and guidance should go beyond the examples that have been offered. Furthermore, the proposed QMS infrastructure does not consider incorporating self-improving QMSs through the use of clinical technology at study sites. One of the largest investment assets in clinical trials is operationalizing the study site. Incorporating quality feedback systems (fueled by clinical technology) that enhances communications between Sponsors and sites, facilitate site staff to automatically resolve quality issues as they arise, rather than depending on one-off engagements with CRAs. Moreover, a self-improving QMS not only saves a tremendous amount of resources, but it also enables the Sponsor to ameliorate quality oversight, and extends stakeholder accountability all the way down to site personnel. Finally, the important area of vendor oversight is not addressed at all. Deficiencies in vendor oversight often lead to compliance issues and is now becoming both FDA and EMA inspector priorities. Implementing a QMS While the publication has proposed a solid and comprehensive issues management methodology via a QMS, there are general complications that sponsors must consider during execution. Specifically, defining and interpreting KPIs/KRIs can result in reporting inaccuracies, or misfires that would impact the quality of management analytics and visualizations of the QMS program. For example, Sharon Reinhard, President of Clinical Compliance indicated in a previous interview with Applied Clinical Trials that issues interpretation varies vastly when a CRA looks at an issue versus an auditor; a CRA can completely miss a protocol violation, whereas an auditor would capture it by questioning unusual data during an audit. Accordingly, it could be a challenge to properly quantify clinical program risk due to the subjective nature of GCP, and ‘issues that matter’ interpretation. Summary The TransCelerate paper offers plenty of robust discussion on issues management, however, the process needs to include specific details and enhanced methodologies in order to comprehensively cover all aspects of a solid QMS. We are excited to see how the TransCelerate tools will develop. Moe Alsumidaie, is a regular contributor to and member of Applied Clinical Trials Editorial Advisory Board. Beat Widler, PhD, and Peter Schiemann, PhD are Managing Partners at Widler & Schiemann Ltd. References
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