Evaluation of the Effectiveness of Additional Risk Minimization Measures for Voriconazole in the EU: Findings and Lessons Learned from a Healthcare Professional Survey

Abstract

Background Voriconazole is an extended-spectrum antifungal agent approved for the treatment and prophylaxis of invasive aspergillosis and other serious fungal infections. In 2014, additional risk minimization measures (aRMM) consisting of a Healthcare Professional (HCP) Question and Answer (Q&A) Brochure, HCP Checklist, and Patient Alert Card were implemented on a rolling basis across the European Union (EU) to mitigate three key risks with voriconazole: phototoxicity, squamous cell carcinoma (SCC) of the skin, and hepatotoxicity. The risks of phototoxicity and hepatotoxicity have been documented in the Summary of Product Characteristics (SmPC) since voriconazole was first approved in the EU in 2002. However, the risk of SCC of the skin was a more recent addition to the SmPC (added in 2010). Objectives We evaluated the effectiveness of the aRMM, as per EU Good Pharmacovigilance Practices Module XVI, via a survey of HCPs. Methods An online survey was conducted among specialty care HCPs in 10 EU countries who had received by mail aRMM tools 12 months previously. Survey questions evaluated HCPs' receipt and utilization of aRMM tools, and knowledge of the three risks. Results Of 27,396 HCPs invited to participate, 332 eligible respondents completed the survey (response rate: 447/26,735; 1.7%). In total, 19.6% of respondents recalled receiving the HCP Q&A Brochure, 22.6% the HCP Checklist, and 25.9% the Patient Alert Card. HCPs had a high level of knowledge of phototoxicity and hepatotoxicity; however, knowledge of SCC was lower. Knowledge of the three risks and self-reported risk minimization behavior was slightly improved in those who had read the HCP Q&A Brochure compared with those who had not. Conclusion The effectiveness of the voriconazole aRMM cannot be meaningfully inferred from the results due to the low survey response rate. The assessment indirectly points to the SmPC or other resources being the main source of risk information for HCPs. Engaging HCPs before designing and implementing an aRMM program is crucial to ensure an effective and focused program. (EU PAS registration number: EUPAS12624).

Effectiveness of risk minimisation measures for valproate: A cross‐sectional survey among physicians in Europe

“…The highest percentage of respondent physicians was GPs followed by other specialities (eg, neurologists). Compared to other survey studies measuring the effectiveness of RMMs in the European region, our study showed comparatively higher response rate 17‐19 . Though there was an intentional over‐sampling in Sweden and Spain, and of less frequent specialities as neurologists, psychiatrists and an under‐sampling in Germany, France and of GPs, the sample data were not adequate for generalisability to the overall target population.…”

Effectiveness of the golimumab educational program in ensuring healthcare professionals’ awareness of risks described in the European risk management plan

“…The present study also did not prespecify a threshold for adequate risk awareness, nor did the vast majority of previous HCP risk awareness survey studies. Nonetheless, as in the present study, most of the previously reported HCP risk awareness survey studies characterized the reported awareness levels as being ‘high’ or ‘very high’, 10–14,16 with one study simply stating that the ‘majority’ of HCPs responded as being aware of the risk surveyed. 15 Defining a target risk awareness threshold that can be considered adequate is a relevant topic for future research.…”

“…7–9 Previous studies have reported HCP recall of receipt of any printed materials distributed by pharmaceutical companies concerning drug risks as being generally low. 10–12 Nevertheless, the same HCP survey studies reported high levels of HCP risk awareness or an acceptable level of appropriate prescribing behavior.…”

“…The high overall level of risk awareness observed in the present study was comparable to that reported for similar studies surveying HCP risk awareness for other drugs for which additional educational materials had been distributed. 10–16 All of these studies reported risk awareness levels that generally ranged above 80%. 10–16 The two previous publications of HCP survey studies examining risk awareness for other anti-TNF-α antibodies, for which EPs had been implemented, reported very similar risk awareness levels to those observed in this study.…”

“…10–16 All of these studies reported risk awareness levels that generally ranged above 80%. 10–16 The two previous publications of HCP survey studies examining risk awareness for other anti-TNF-α antibodies, for which EPs had been implemented, reported very similar risk awareness levels to those observed in this study. 13–14 The question arises as to what level of risk awareness is considered adequate from a sponsor`s as well as a regulator`s perspective.…”