Assessment of pharmacovigilance guidelines in the Southern African Development Community: A document review.

BACKGROUND: Lack of harmonization in pharmacovigilance (PV) practice in resource-limited states in Africa has led to differentiation and marginalization, thus creating an environment where weak or absent PV systems may benefit from regional guidelines. PURPOSE: To compare the PV guidelines of Southern African Development Community (SADC) member states to international guidelines and identify areas for improvement for aligning PV practice within the SADC region. METHODS: We utilized a 73-item checklist to assess the PV guidelines of the SADC member states. Checklist parameters were rated using binary scoring. RESULTS: Only seven (Botswana, Mauritius, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe) of the 16 SADC member states had guidelines to assess. Of these, only four had supporting legislation. All seven national medicines regulatory authorities (NMRA)'s guidelines required reporting of local serious adverse drug reactions (ADRs). Four NMRAs implemented device vigilance; none specified submission timelines for ADRs associated with substandard or falsified medicines. Only three NMRAs required electronic transmission of individual case safety reports in the E2B format. Five NMRAs mandated safety monitoring during interventional clinical trials. Five NMRAs required aggregate reporting through periodic safety update reports. Only two NMRAs required submission of the development safety update report. Regarding risk management, four NMRAs required notification of actions taken by foreign NMRAs and four NMRAs expected to review Dear Healthcare Professional Letters before distribution by the marketing authorization holder. CONCLUSIONS: Areas for improvement of guidelines to establish common process standards and allow for synchronized submissions of comparable data to SADC NMRAs are provided.

Development of a checklist for the assessment of pharmacovigilance guidelines in Southern Africa: a document review.

Introduction: National regulatory systems in Southern Africa reflect various stages of maturity, and pharmacovigilance (PV) practices are not aligned. In the absence of guidance for formulating PV guidelines in Southern African Development Community (SADC) countries, this study aimed to create a checklist that may be used to assess the rigour of PV guidelines in this region and provide guidance for the National Medicines Regulatory Agency (NMRA) authors. Methods: A document analysis was performed based on harmonised international guidelines (n = 22) that prescribed methods of PV regulation to identify themes and items to incorporate into a checklist. The contextualisation of the checklist to the African pharmaceutical environment was accomplished by referencing peer-reviewed journal articles (n = 7). The checklist was subjected to face and content validation by non-experts and PV experts. Results: The document review yielded 5 themes, 18 sub-themes, and 73 items structured into the checklist. Themes encompassed PV systems, definitions, individual case safety reporting, aggregate reporting, and risk management. Under PV systems, aspects of the quality management system were outlined, that is, the legal basis for PV, a description of the marketing authorisation holder's (MAH's) PV system, archiving of data, contracting of PV tasks, and the duties of the person responsible for the MAH's PV obligations. Definitions of the key terms and major stakeholders were identified. Reporting of individual case safety reports (ICSRs) was explicated by considering the criteria for reporting, categories of reportable information, expedited reporting requirements, reporting timelines, and ICSR reporting format. Aggregate report submission during the development and post-marketing phases was addressed. Risk management encompassed signal detection, re-evaluation of the benefit-risk ratio, the safety decision-making process, risk management planning, risk minimisation and safety communication. Conclusion: The developed checklist can contribute towards assisting SADC NMRAs to formulate national PV guidelines that reflect current international practice, with local context incorporated. Plain Language Summary: Developing a checklist for the evaluation of medicine safety guidelines in Southern Africa Introduction: In Southern African Development Community (SADC) countries, the guidelines for medicine safety [pharmacovigilance (PV)] that marketing authorisation holders (MAHs) and healthcare professionals need to adhere to, are not aligned. We saw the need to develop a checklist that can be used to evaluate these guidelines.Methods: We studied international documents issued by the World Health Organization (WHO), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the Council for International Organizations of Medical Sciences (CIOMS) and the European Medicines Agency (EMA). On the organisational websites, we obtained 22 documents and identified 73 checklist items. All the items were arranged under 5 themes and 18 sub-themes to create the checklist. We adapted the checklist to the local context by using seven journal articles addressing PV concerns in Africa. Experts checked the content and usability of the checklist.Results: The themes were PV systems, definitions, individual case safety reporting (ICSR), combined reporting and risk management. PV systems had six sub-themes: legal structure, description of the MAH's PV system, contractual agreements, information storage, the qualified person responsible for PV (QPPV) and where the QPPV is located. We included the definitions of keywords and role-players. The ICSR theme had five sub-themes, i.e. criteria for reporting, categories of reportable information, expedited reporting, reporting timelines, and reporting format. Submission of summary reports comprised an overview of the safety profile of a medicine once it is approved by regulators, as well as during clinical trials. Risk management included signal detection, re-evaluation of the benefit-risk ratio, safety decision-making process, risk management planning, risk minimisation, and safety communication. The checklist is applied by allocating yes/no scoring per item.Conclusion: The checklist may be used by regulators within SADC to assess their PV guidelines for alignment with international standards and suitability to the local environment.

Completeness of pharmaceutical industry insulin adverse event reports from Africa and the Middle East.

BACKGROUND: Growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate understanding adverse event reporting in these regions. We assessed pharmaceutical industry insulin individual case safety report (ICSR) completeness and completeness-associated variables. RESEARCH DESIGN AND METHODS: The observational cross-sectional study, set in an insulin-manufacturing company's safety database, assessed vigiGrade® completeness scores of African and Middle Eastern post-marketing ICSRs from January to December 2018, and case variables effects on completeness. Low vigiGrade® scores indicated poorly documented ICSRs. RESULTS: We analyzed 4854 ICSRs; 59.8% from the Middle East. The mean vigiGrade® score was 0.58. Middle Eastern ICSRs had higher mean scores than African ICSRs (0.65 vs. 0.46, p<0.001). Scores peaked at 0.32, 0.70, and 1.00 for Middle Eastern ICSRs compared to 0.35 and 0.50 for African ICSRs. Middle Eastern serious (0.77 vs. 0.47; p<0.001) and solicited (0.70 vs. 0.48; p<0.001) ICSRs had higher mean scores than African ICSRs. Mean scores were highest for Middle Eastern physicians (0.89) and other healthcare professionals (0.82), whereas, in Africa, scores were highest for consumer- (0.47) and pharmacist-reported ICSRs (0.47) (p<0.001). CONCLUSIONS: Middle Eastern pharmaceutical industry insulin ICSRs were documented with greater detail than African ICSRs. Seriousness, report source, and reporter type significantly impacted ICSR completeness.

Adherence and clinical outcomes of HIV patients switching to a fixed-dose combination regimen.

Background: The efficacy of antiretroviral therapy (ART) is monitored using clinical markers such as viral load (VL) and CD4 counts. Adherence to ART has been associated with viral suppression and improved clinical outcomes. Objectives: To determine the relationship between adherence status with multiple-tablet regimens (MTR) and fixed-dose combination (FDC) regimens, to weight, CD4 count and VL of patients living with HIV. Method: An observational, descriptive study was conducted on a closed cohort of patients living with HIV and attending a primary health care clinic in Northern Cape in South Africa between 01 January 2013 and 31 December 2015. Patients were on an MTR and changed to an FDC regimen. Adherence was measured using the medicine possession ratio (MPR). Results: Statistically significant differences exist between the mean MPR of the 30-day (p = 0.0308) and 28-day supply (p < 0.0001) of the MTR when compared to FDC regimen. No statistically significant differences could be found between adherence and clinical outcomes such as weight, CD4 count and VL for either MTR or FDC regimens. The suppressed VL values measured for MTR were n = 299 (89.25%) and n = 415 (93.05%) for FDC regimen. Conclusion: Adherence improved when patients were switched to FDC, but no statistically significant differences in clinical outcomes measured as weight, CD4 count and VL between adherence status and regimen type could be found. Contribution: This study contributes to much-needed information about ART adherence and clinical outcomes (such as weight, CD4 count and VL) of adult HIV-positive patients in a public healthcare clinic in the Northern Cape, South Africa.

Individual Case Safety Reports Analysis for Patients with Diabetes Mellitus on Insulin in Africa and the Middle East.

BACKGROUND: The growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate an understanding of adverse event (AE) reporting in these regions. OBJECTIVE: The aim of the study was to provide an AE reporting overview in patients using insulin in Africa and the Middle East by characterizing and comparing individual case safety reports (ICSRs) features. METHODS: The cross-sectional study analyzed ICSR data from a global pharmaceutical company's pharmacovigilance database for January to December 2018 to describe and compare patient demographics, report sources, reporter types, ICSR seriousness, suspect products, indication for insulin use and AE preferred terms, by country. RESULTS: Overall 7076 ICSRs were analyzed, 63.6% from the Middle East. Most ICSRs were nonserious (91.5%), from solicited sources (83.5%), and reported by consumers (70.7%). Patients from the Middle East were, on average, 34.2 years of age, had gestational diabetes mellitus as indication (64.3%), insulin detemir as suspect product (76.5%), and exposure during pregnancy as AE preferred term (89.1%). Patients from Africa were 48.1 years old on average, a higher proportion of type 2 diabetes mellitus was observed (52.2%), human insulin was the suspect product (51.6%), and blood glucose increased the AE preferred term (23.1%). Few macrovascular and microvascular complications were reported (< 1% in both regions). Associations between the region and patient age, gender, report sources, reporter types, indications for insulin use, suspect products, and AE preferred term were significant (p < 0.001). CONCLUSION: ICSRs features were region-specific and dependent on patient age, gender, report sources, reporter types, suspect products, and AE preferred terms.