As part of its routine pharmacovigilance work, the Saudi Food and Drug Authority (SFDA) assess the adherence to risk minimisation measures (RMMs) to ensure safe medication use in the post-marketing setting. RMMs may be classified as either routine or additional RMMs. Routine RMMs are standard measures that are required for all medicinal products, such as patient information leaflets, whereas additional RMMs, such as prescriber and patient guides, are extra measures to address specific safety issues and are requested only if they are considered essential to maintain a positive risk-benefit balance of a medicinal product.
According to the SFDA guideline on good pharmacovigilance practices, if a particular RMM is proven to be ineffective or is causing excessive or undue burden on patients or the healthcare system, an alternative RMM method should be considered. Previous studies have highlighted challenges in healthcare providers adhering to additional RMMs (aRMMs). Therefore, it is essential to periodically monitor the healthcare providers’ adherence to aRMMs, and here is where medication utilisation evaluations (MUEs) may help.
The MUE is a commonly used performance tool by hospitals for assessing medication use processes or medication treatment response, with a focus on patient outcomes. Its overall objective is to improve the safety and appropriate use of medications by assessing what works well and where there is room for improvement. However, research on their potential role to assess adherence to aRMMs is limited.
A multicenter cross-sectional study conducted by SFDA assessed the utility of MUEs as a tool to evaluate adherence to approved aRMMs for four medications: Bosentan (for pulmonary arterial hypertension), Clozapine (a psychiatric medication), Fingolimod (an immunosuppressant), and Pirfenidone (for idiopathic pulmonary fibrosis). The study was carried out across 10 tertiary hospitals in Saudi Arabia between February 2021 and December 2022.
Of the 19 invited hospitals, 10 agreed to participate. Regional pharmacovigilance officers from these sites collected data using standardised tools developed by the SFDA. To ensure consistent methodology and understanding of MUEs and aRMMs, two national workshops were conducted. Data collection forms captured patient demographics, prescriber specialty and rank, indication, dosing, presence of drug interactions or adverse drug reactions (ADRs), and adherence to required laboratory monitoring, such as liver function tests and blood counts, at timepoints specified in the product-specific aRMMs. Adherence to aRMMs was defined as meeting three criteria: medication prescription by an appropriate specialist at the correct dose, completion of required laboratory tests at specified intervals (before, during, and/or after treatment), and when applicable, following recommended ADR management protocols. Adherence was considered successful only when all criteria were met.
Data from 411 patients were collected and assessed by two independent SFDA investigators. The MUEs revealed that overall adherence to aRMMs was low: 7.3% for Fingolimod, 12.2% for Clozapine, 36.4% for Pirfenidone, and 29% for Bosentan. They also uncovered several safety concerns for the medications tested: drug-induced liver injury for three of the four medications (nine cases with Fingolimod, three with Pirfenidone, and four with Bosentan), liver failure (11 Fingolimod cases), and clinically significant drug-drug interactions (seven Fingolimod cases).
This study demonstrates that MUEs are valuable tools for regulatory authorities to assess real-world adherence to additional risk minimisation measures. The findings reveal significant compliance gaps, with overall adherence rates ranging from 7.3% to 36.4% across the four medications studied. Beyond measuring adherence, MUEs effectively identified safety concerns including drug-induced liver injury and clinically significant drug interactions, demonstrating their dual functionality as both compliance assessment and signal detection tools. These results support implementing routine MUE-based assessments as a standard component of post-marketing surveillance, enabling regulators to bridge the gap between theoretical risk management plans and their practical implementation in clinical settings.
Read More:
"Guideline on good pharmacovigilance practices: Module XVI – Risk minimisation measures: selection of tools and effectiveness indicators", EMA, 2017.
Afanasjeva J et al., "ASHP Guidelines on Medication-Use Evaluation", AJHP, 2021.
"Drug Utilization Review", AMCP, 2019.
"Guideline on Good Pharmacovigilance Practices (GVP)", SFDA, 2023.
