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.

The completeness of adverse drug reaction reports in South Africa: An analysis in VigiBase®.

BACKGROUND: Spontaneous reporting is regarded as a cornerstone of pharmacovigilance (PV) but presents many limitations, including varying quality and completeness of information, which is essential for causality assessment. AIM: This study aimed to evaluate the completeness of adverse drug reaction (ADR) reports in South Africa based on the vigiGrade completeness score. SETTING: The South African Health Products Regulatory Authority (SAHPRA). METHODS: A cross-sectional, descriptive study of all reports received by SAHPRA and submitted to VigiBase® in 2017 was conducted. A report with a vigiGrade score 0.8 is considered well-documented. RESULTS: The mean completeness score for the 8438 reports received was 0.456 (s.d. = 0.221). Only 11.3% of reports had a completeness score 0.8. The completeness of reports submitted by consumers professionals did not significantly differ from reports by physicians, pharmacists or other healthcare professionals (d ≤ 0.2). Reports of reactions that resulted in death (M = 0.572, s.e. = 0.007), disability (M = 0.491, s.e. 0.033) or were life threatening (M = 0.474, s.e. = 0.013) had a medium to large practically significant effect (0.5 ≥ d ≤ 0.8) on the completeness score compared with reports of congenital anomaly (M = 0.348, s.e. = 0.089). CONCLUSION: The completeness of reports submitted by consumers is comparable to those submitted by healthcare professionals. The completeness of reports was low and multiple measures to improve reporting are recommended.Contribution: This study describes the completeness of ADR reports in South Africa and the results can be used to improve training.

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.

Coexisting Conditions among Children and Adolescents with Cancer in a Section of the South African Private Health Sector: Perspectives from Drug Utilization Data.

Coexisting conditions are relatively common in children with cancer, however, there is a paucity of information on the prevalence of coexisting conditions in children with cancer in South Africa. This cross-sectional study aimed at investigating the common coexisting conditions occurring in children and adolescents younger than 19 years undergoing cancer chemotherapy in a section of the South African private health sector. Medicine claims data from 1 January 2008 to 31 December 2017 were queried to identify coexisting conditions using the International Classification of Diseases, Tenth Revision (ICD-10) codes indicated on reimbursed claims. Where ICD-10 codes per claim were non-specific, the pharmacological drug classes of non-cytotoxic medications claimed alongside these codes were categorized using the Monthly Index of Medical Specialties (MIMS) classification system and analyzed using the drug utilization 90% (DU90%) principle. Analysis of sub-pharmacologic drug classes was stratified according to gender and age groups. The reimbursement category of these medicines was noted. Data were analyzed descriptively. A total of 173 participants were included in the study. ICD-10 codes were available for 13.65% (N = 2631) of medicine claims. Diseases of the respiratory system (J00-J99, 7.15%), gastrointestinal tract (K00-K95, 1.60%), and skin disorders (L00-L99, 0.95%) were the most prevalent specific diagnoses identified. Non-specific ICD-10 codes were recorded on 86.35% (n = 2272) of non-cytotoxic medicine claims. The most frequently utilized pharmacological classes of medications included antimicrobial agents (17.40%), respiratory system agents (13.91%), and analgesics (10.64%). As determined from ICD-10 codes and medication claimed on reimbursed claims, children and adolescents being treated for cancers mostly suffered from acute conditions, in particular, microbial infections and diseases of the respiratory system. This indicates the need for the integration of antimicrobial surveillance programs into childhood and adolescent cancer care to curb antimicrobial infections.

Childhood cancers in a section of the South African private health sector: Analysis of medicines claims data.

BACKGROUND: Although childhood cancers are rare, increases in incidence have been observed in recent times. There is a paucity of data on the current incidence of childhood cancers in South Africa. AIM: This study described the epidemiology of childhood cancers in a section of the private health sector of South Africa, using medicines claims data. SETTING: This study was designed on a nationally representative medicine claims database. METHOD: A longitudinal open-cohort study employing children younger than 19 years and diagnosed with cancers between 2008 and 2017 was conducted using medicine claims data from a South African Pharmaceutical Benefit Management company. Cases were identified using International Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes C00 to C97, together with a medicine claim reimbursed from oncology benefits. Crude incidence rates were calculated per million persons younger than 19 years on the database and standardised using the Segi 1960 world population. Temporal trends in incidence rates, analysed using the joinpoint regression, were reported as annual percentage changes (APCs). RESULTS: Overall, 173 new cases of childhood cancers were identified in the database, translating into an age-standardised incidence rate (ASR) of 82.3 per million. Annual incidence of cancer decreased from 76.7 per million in 2008 to 58.2 per million in 2017. More incident cases were identified in males (68.8%). The highest proportion of incident cases was recorded for leukaemias (39.9%), the 5-9 year age group (34.1%) and the Gauteng Province (49.7%). CONCLUSION: The incidence of childhood cancers decreased over time in the section of the private health sector studied. Leukaemias were the major drivers of childhood cancer incidence.

Childhood cancers in a section of the South African private health sector: Analysis of medicines claims data

Background: Although childhood cancers are rare, increases in incidence have been observed in recent times. There is a paucity of data on the current incidence of childhood cancers in South Africa.Aim: This study described the epidemiology of childhood cancers in a section of the private health sector of South Africa, using medicines claims data.Setting: This study was designed on a nationally representative medicine claims database. Method: A longitudinal open-cohort study employing children younger than 19 years and diagnosed with cancers between 2008 and 2017 was conducted using medicine claims data from a South African Pharmaceutical Benefit Management company. Cases were identified using International Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes C00 to C97, together with a medicine claim reimbursed from oncology benefits. Crude incidence rates were calculated per million persons younger than 19 years on the database and standardised using the Segi 1960 world population. Temporal trends in incidence rates, analysed using the joinpoint regression, were reported as annual percentage changes (APCs). Results: Overall, 173 new cases of childhood cancers were identified in the database, translating into an age-standardised incidence rate (ASR) of 82.3 per million. Annual incidence of cancer decreased from 76.7 per million in 2008 to 58.2 per million in 2017. More incident cases were identified in males (68.8%). The highest proportion of incident cases was recorded for leukaemias (39.9%), the 5­9 year age group (34.1%) and the Gauteng Province (49.7%).Conclusion: The incidence of childhood cancers decreased over time in the section of the private health sector studied. Leukaemias were the major drivers of childhood cancer incidence