Implementation of risk based monitoring into academic led clinical trials in Ireland
Introduction: In November 2016, the International Conference on Harmonsation (ICH) published a requirement for sponsors to develop a systematic, prioritised, risk-based approach to monitoring clinical trials. This process is more commonly known as Risk Based Monitoring (RBM). However, evidence suggested that a gold standard validated approach to RBM did not exist and it was unclear how sponsors would introduce RBM into their clinical trials units (CTUs). In 2014, Ireland, unlike countries such as Switzerland and the UK, did not have a national strategy to support the introduction of RBM into its publicly funded, academic-led CTUs. The absence of a national strategy and gold standard RBM approach meant it was not clear how RBM would be implemented in CTUs. Therefore, the overarching aim of this thesis was to develop, implement and evaluate a quality improvement intervention to support the introduction of RBM into academic-led clinical trials in Ireland. Methods: This thesis employed a multi-method research strategy directed by the Knowledge to Action (KTA) framework over four years from October 2014 to October 2018. The KTA framework is a conceptual framework to assist the translation of knowledge into sustainable, evidence-based interventions. This thesis used a range of research methods, implemented in four separate sequential phases, to address different components of the KTA framework which primarily involve knowledge creation and knowledge translations. The four phases first involved systematically reviewing the existing evidence of RBM methods. Then, in a mixed method study, I explored the attitudes, and perceived barriers and facilitators to the implementation of RBM in academic-led clinical trials in Ireland. Next, I did a document analysis study to examine the experience of monitoring in a clinical trial. Finally, I developed the quality improvement study by combining the results of the three earlier phases to identify the most appropriate quality improvement intervention to support RBM use in academic led clinical trials in Ireland. Results: The systematic review showed several tools exist to support the implementation of RBM. The mixed methods study showed a need for training and regulatory endorsed guidelines to support the implementation of RBM in academic-led clinical trials. The document analysis showed that on-site and centralised monitoring can be used simultaneously to fulfil ICH GCP’s seventeen monitoring requirements. The findings of these three studies were combined and a brief, face-to-face, interactive education workshop was identified as an effective way to encourage RBM tool usage among clinical researchers working in academic-led clinical trials in Ireland. Conclusion: Applying the KTA framework to empirical data has led to an intervention that is implementable in clinical practice and has the potential to positively change monitoring practices of clinical researchers. This thesis provides critical evidence on the complexities associated with implementing RBM in academic-led clinical trials. It provides practical recommendations to guide clinical researchers who wish to perform RBM.
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