EVALUATING AND IDENTIFYING CHARACTERISTICS OF EFFECTIVE RISK MINIMISATION MEASURES

General Introduction Risk minimisation measures (RMMs) are interventions designed to prevent or reduce the occurrence and severity of adverse drug reactions.. To further enhance the field of risk management, it is generally acknowledged that there is a need for more high-quality studies to inform regulatory decision-making and to understand what works and what does not. This thesis aimed to identify characteristics of effective risk minimisation strategies and recommend improvements to risk minimisation, specifically targeting regulators and guiding future research. Chapter 2 investigated the need for risk minimisation beyond product information to reduce hyponatraemia caused by the inappropriate use of physiological hypotonic fluids. One study focused on physicians, while the other targeted nurses. A cross-sectional survey of Danish emergency physicians and nurses in 2019 revealed significant knowledge gaps and inappropriate prescribing practices. For example, only 29.4% of physicians selected the correct treatment for severe hyponatraemia, which is a medical emergency. Although not responsible for prescribing, nurses play a vital role in assisting and ensuring appropriate IV fluid therapy. However, they also demonstrated significant knowledge gaps. Beyond providing evidence of the need for further RMMs, the study also provided valuable insights for tailoring the needed intervention. Chapter 3 presents findings from two studies, each evaluating a distinct RMM using different methodologies. First, a survey study in 2021 evaluated a treatment guide to reduce hyponatraemia. Despite significant development efforts, the intervention failed due to poor dissemination, with only 22% of the target audience receiving the guide. Knowledge improvements and prescribing practices did not meet predefined success criteria, emphasizing that effective implementation is as crucial as content quality. The second study assessed measures introduced by the European Medicines Agency (EMA) to restrict combined use of renin–angiotensin system (RAS) blockers. An interrupted time series analysis of 2008–2018 data revealed a declining trend in RAS blocker co-dispensing both before and after the intervention, indicating limited additional regulatory impact. These findings highlight challenges in isolating the effects of RMMs when evidence-based changes are already adopted by medical communities. Chapter 4 examined the Danish Medicines Agency’s (DKMA) implementation of electronic Direct Healthcare Professional Communication (DHPC) distribution and physicians’ preferences on safety communication. A survey in 2022, found that total awareness of DHPCs rose to 81%, nearly 20% higher than a prior study, indicating that the communication of DHPCs improved since the DKMA took over the responsibility for their distribution from pharmaceutical companies. Additionally, physicians preferred digital communication via trusted sources like the DKMA. Drawing from our findings regarding preferences, we recommend enhancing safety communications by using information sources already popular among the target audience and supplementing primary channels with methods like point-of-care alerts to improve uptake. The general discussion highlights the findings and challenges of evaluating RMMs. Current evaluations often rely on surrogate outcomes, such as prescribing practices, due to difficulties in using direct safety outcomes. Survey studies face challenges like non-response bias, which require proactive strategies such as incentives and reminders to mitigate. A lack of clear success thresholds also complicates assessments, underscoring the need for transparency and supplementary evidence to support conclusions. Our research highlights that RMM success depends on strong implementation, requiring methods from implementation science, such as active dissemination, repeated interventions through diverse communication methods, and enduser involvement. Regulators must acknowledge the interdisciplinary complexity of risk management. Furthermore, enhancing the effectiveness of RMMs requires high-quality studies, rigorous feasibility assessments, and the evaluation of regulatory guidelines to ensure they support these goals.