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TransCelerate’s recently published article in a DIA publication covered issues management in clinical trial Quality Management Systems (QMS). Abbvie’s Susan Callery-D’Amico speaks to us about TransCelerate’s QMS Initiative and Issue Management.
TransCelerate recently published an article in (DIA)’s Therapeutic Innovation & Regulatory Science Journal about issues management in clinical trial Quality Management Systems (QMS), and we analyzed the details of the publication earlier this month. In this interview, Susan Callery-D’Amico, VP of R&D Quality Assurance at Abbvie, will elaborate on TransCelerate’s QMS Initiative, specifically Issue Management.
Moe Alsumidaie: You’ve identified a new concept in risk categorization via ‘issues that matter.’ Can you tell us how this concept came about?
Susan Callery-D’Amico: As you are aware, Issue Management is one of the elements of TransCelerate’s Conceptual Framework for a Clinical QMS. In order to further an understanding of the problem we were attempting to solve; it was important to engage TransCelerate’s member companies through a series of direct discussions and where we collected data on the management of issues. From the data collection, we identified considerable variability in the way companies managed issues, and it became clear that there is no consistency across the industry. Some companies would take every issue and automatically address it with CAPAs and therefore experienced as they reported “death by CAPA.” There was a theme that emerged across member companies, that despite focus of resources and technology advances, the prevalence of re-occurrences and impact of issues creates re-work, diverts needed resources and potentially reduces confidence in the ability to effectively adjudicate issues.
The TransCelerate QMS Issue Management framework includes ‘points to consider’ supporting a company developing a triage mechanism with thresholds. Further considerations are noted that may arise with regard to the development of threshold(s), which a particular sponsors may further tailor to take into account its own policies, procedures and risk-tolerance. Lastly, how the definition of an ‘issue that matters’ can be applied.
MA: What about issues that don’t matter?SCD: It is a natural tendency to want to define an issue that does not meet the definition of an “issue that matters” as an issue that does not matter. This is simply not the case because there could be important information from the issues that have been filtered out as not meeting the definition and thereby held in a “filtered issue repository” for further evaluation. Rather, those issues move through a ‘filtered issues repository,’ which can be managed through risk-based activities. A company will want to hang onto ‘issues that don’t matter’ because in aggregate there could be an ‘issue that matters’ in them, or over time, these are issues that should perhaps be addressed; this can all be done through training and analytics. The ‘issues that matter’ approach enables a sponsor to focus on critical issues, and apply a robust CAPA process to address them, measure them, and prevent them from reoccurring.
MA: Please elaborate on how an enterprise operationalizes the ‘issues that matter’ approach. Can you tell us more about what may come in the coming toolkits?SCD: The QMS Issue Management framework allows a company to develop its own thresholds for identifying and triaging issues. This conceptual approach requires critical thinking and evaluation that is required in upfront planning to build the thresholds. In addition to the Issue Management framework, TransCelerate has developed a companion set of toolboxes that facilitate a company’s operational efforts with points to consider when developing on implementation and execution of an issue management system when developing thresholds, and trending and analytics.
Some of the topics in the toolkits will include information on what a sponsor might consider in developing an escalation pathway, how it could set up thresholds by consolidating information that is already in the public domain, various ways of investigating identified issues, going through the CAPA process, root cause analysis, and how to perform good effectiveness checks. Additionally, there will be information on how to correct and prevent issues, and how it all fits into a clinical QMS.
MA: The topic of vendor oversight was not mentioned in the paper. How can you apply the ‘issues that matter’ approach towards vendor oversight?SCD: The QMS framework leaves room for a company to develop its own thresholds, which includes vendor oversight. When building a threshold, whether it is internal or through a vendor, requirements must be determined and established upfront. A company can then build in its thresholds where it would make something like an "acceptable error" or "acceptable issue" list in which by the time it experiences the fifth occurrence or so, it would probably categorize it as an ‘issue that matters’ which will result in a CAPA. Vendor oversight can be called out separately, but, it should be a part of how a company is going to build its thresholds in its escalation pathway, and working with that vendor to understand what is considered an ‘issue that matters.’
To elaborate, typically with vendor oversight, a company establishes specific expectations contractually upfront. For example, if a monitoring visit is supposed to occur because of a specific safety threshold trigger, and evaluation of the occurrence of the trigger and subsequent documentation generally would need to occur. If patients were not consented properly or there were several serious adverse events that were not adequately reported, a sponsor needs a robust escalation process to fulfill obligations as sponsor oversight.
MA: Issues identification and interpretation can be quite subjective. How can the ‘issues that matter’ approach maintain objectivity?SCD: Training staff is a critical aspect that can reduce subjectivity during potential risk evaluations. Having a process and established criteria based upon a company’s policy, procedures, and risk tolerance allows an evaluation of issues where a triage will occur and a filtering to determine “issues that matter” will be a critical task for each company to complete. A company needs to start somewhere and, to be able to do this, it helps to set the expectations from the beginning. Issues interpretation will certainly vary by different personnel, and how that is translated and moves into an ‘issue that matters’ is difficult and it will take diligent surveillance, training and quite a bit of effort to ensure that this is done properly. While TransCelerate defined “Issues That Matter” in the framework, it is up to each sponsor company to determine its own criteria in establishing an issue management triage and thresholds in order to retain filtered issues for further evaluation that will include trending and analytics over time. In the end, an effective issue management framework is essential for maintaining a control in a research and development enterprise. It will enable the efficient identification, correction, and mitigation of potential risks. In addition, trending of filtered issues will enable continuous improvement, and for moving the needle on quality improvement and oversight.