Smart Safety Surveillance (3S): Multi-Country Experience of Implementing the 3S Concepts and Principles.

INTRODUCTION: The Smart Safety Surveillance (3S) concept is based on the understanding that, when faced with competing pharmacovigilance priorities, countries will have to invest judiciously, by focusing on new priority products, sharing work and resources with other countries when possible and building national competence for those activities that cannot be delegated. METHOD: The 3S principles were applied to Armenia, Brazil, Ethiopia, India, Peru and Thailand using three priority products: bedaquiline, rotavirus vaccine and tafenoquine. A baseline assessment of pharmacovigilance preparedness was used to identify gaps and establish a work plan. The impact was measured by comparing pre and post 3S-intervention outcomes, which included the number and quality of reports (completeness scores) in the WHO global database of Individual Case Safety Reports, VigiBase, and number of structural indicators met. The implementation period was 9-18 months, ranging from March 2018 (earliest started) until May 2020 (latest). RESULT: An increase in adverse drug reaction (ADR) reporting was demonstrated in Armenia (bedaquiline), Brazil (TB and malaria medicines), India (rotavirus vaccine) and Ethiopia (TB medicines). Completeness scores were above 0.5 at baseline in all countries, and reports improved in quality for Brazil (TB), Peru (malaria), Thailand (malaria) and India (immunization). The number of structural indicators met increased by more than double for Ethiopia. Ethiopia and India demonstrated an increased capacity for signal detection and signal evaluation. Armenia, Brazil, Peru and Thailand showed increased capacity to assess risk management plans following the implementation of 3S principles. CONCLUSION: The 3S concept has demonstrated success in different ways across the six countries. Activities focused on three products for a proof of concept of the 3S principles, with the expectation that the project impact will be sustained through strengthened systems, to guide pharmacovigilance activities of other products in the future. It is important to continue monitoring the countries to understand if the gains and successes of the current 3S project are sustainable.

Characterization of Statin-Associated Myopathy Case Reports in Thailand Using the Health Product Vigilance Center Database.

BACKGROUND: HMG-CoA reductase inhibitors [statins], a widely prescribed cholesterol-lowering therapy, are associated with muscle-related adverse events. While characteristics of such events are well documented in Western countries, little data exists for the Thai population. OBJECTIVE: The aim of this study was to determine the characteristics of patients, type and dosing of statin, and to identify patterns of drug use that may be associated with such adverse events using the national pharmacovigilance database known as Thai Vigibase. METHOD: Muscle-related adverse events involving statins in the Thai Vigibase from 1996 to December 2009 were identified. For each report, the following information was extracted: patient demographics, co-morbidities, detailed information of adverse event, detailed information of suspected drug, treatment and outcome, as well as causality assessment and quality of reports. Descriptive statistics were performed for all study variables. RESULTS: A total of 198 cases of statin-associated muscle-related adverse events were identified. Mean age was 61.4 ± 12.4 years of age and 59.6% were female. Simvastatin, atorvastatin, rosuvastatin and cerivastatin were implicated as the suspected drug in 163 (82.3%), 24 (12.1%), 10 (5.1%) and 1 (0.5%) cases, respectively. Rhabdomyolysis accounted for 55.6% of all muscle-related adverse events. Drug interactions known to enhance such toxicity of statins were identified in 40.9% of the total set of reports. Similar to studies from Western countries, fibrates, HIV protease inhibitors, non-dihydropyridine calcium channel blockers, azole antifungals and macrolides were commonly found in such cases. Interestingly, colchicine has been identified as the second most common drug interaction in our database. Case fatality rates were 0.9, 1.6 and 16.7%, when there were 0, 1 and ≥2 interacting drugs, respectively. CONCLUSIONS: Characteristics of muscle-related adverse events with statins in the Thai population showed some similarities and differences compared with Western countries. Such similarities included advanced age, female sex, certain co-morbidities and drug interactions. While the majority of interacting drugs are well known, a big proportion of cases of statin-colchicine interaction attributed to long-term use of colchicine in Thailand was noted and should be further investigated. Based on these results, an attempt to avoid dangerous and well-known drug interactions among statin users should be implemented nationwide.