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The tools that sponsors use in clinical research must be validated to ensure they work as intended. Regulators refer to the FDA's Code of Federal Regulation Title 21 Part 11 for the validation of electronic data capture (EDC) systems, the International Society for Pharmaceutical Engineering's (ISPE) Good Automated Manufacturing Practice (GAMP) for the validation of systems used in the manufacturing of medicinal products and the Parenteral Drug Association's (PDA) Technical Report 80 for the validation of laboratory equipment. However, centralized monitoring tools that clinical operations use to make quality-related decisions are not explicitly covered in any of these documents. How can...

Risk assessment is an integral part of risk management. In clinical trials, it serves to lay the foundation of risk-based monitoring processes. Regulators currently encourage its use to improve the safety and the quality of clinical trials. In practice, assessing risks is difficult but clinical research professionals must become acquainted with the concept of risk assessment in order to reap the full potential of risk-based monitoring. Regulatory Perspective The FDA’s most recent guidance is fairly specific about the importance of conducting a risk assessment to identify risk and develop a monitoring plan: The risk assessment serves to identify and understand...

The centralized monitoring report is the best channel to share risk signals with clinical trials stakeholders. In addition to being the perfect tool for the review of site-specific Key Risk Indicators (KRI) metrics with clinical operations teams, producing periodic reports ensures the traceability of the centralized monitoring activities for regulatory audit purpose. Reports are also essential for the continuous improvement of centralized monitoring processes.   The TransCelerate BioPharma Initiative specifically states that Monitoring reports should serve as tools for the team members to communicate a concise, high-level summary of monitoring activities, issues and associated actions.  It’s imperative that companies build off...

When using a centralized monitoring approach, Key Risk Indicators (KRIs) metrics are calculated for individual study sites and compared against limits, also known as “thresholds” or “tolerance level”, beyond which sites may be considered abnormal and warrant investigation. Limit values must be carefully chosen to be able to detect risk without triggering too many false signals. Information relevant to the choice of limits can be obtained by executing a trial’s risk assessment and by calculating site-specific KRIs statistical distributions. Below are some points to consider when choosing limits. Limits Based on Risk Assessment Risk identified through the risk assessment should...

Writing an Integrated Quality and Risk Management Plan (IQRMP) involves identifying risk factors and developing a contingency plan to manage the risks that cannot be eliminated. Risk factors can be monitored using Key Risk Indicators (KRI) which are metrics calculated from the collected data associated with risk factors. For instance, most studies consider the AE rate a risk factor and will monitor it on a periodic basis by calculating the site-specific number of adverse events divided by the number of subject-days. A risk signal is typically triggered when a Key Risk Indicator (KRI) metric’s value falls beyond its set limits...