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.

Challenges facing drug utilization research in the Latin American region.

PURPOSE: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region. METHODS: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region. RESULTS: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions. CONCLUSIONS: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system.

Time-to-onset of treatment for hypertension and hyperlipidaemia in South African diabetes mellitus patients: A survival analysis using medicine claims data.

WHAT IS KNOWN AND OBJECTIVE: Hypertension and hyperlipidaemia have high prevalence among diabetics and increase patients' risk of cardiovascular diseases, ultimately affecting prognosis negatively. Medicine claims data have gained prominence in the study of drug-related events and outcomes. There is paucity of publications on the time-to-onset of treatment for these conditions among South African diabetics using secondary data. This study aims to determine the time-to-onset of treatment for hypertension and hyperlipidaemia among diabetics using a South African medicine claims data. METHODS: Survival analysis was conducted using retrospective data of patients enrolled continuously with a Pharmaceutical Benefit Management (PBM) company in South Africa from 1 January 2008 to 31 December 2016. We identified patients based on International Classification of Diseases, Tenth Revision (ICD-10) diagnoses codes for type 2 diabetes mellitus (E11) who were receiving antidiabetic medication according to the National Pharmaceutical Product Index (NAPPI) codes provided by the Monthly Index of Medical Specialities (MIMS) classification code 19.1 (N = 2996). Among these patients, we then selected those who had ICD-10 codes for hypertension (I10, I11, I12, I13, I15, O10 and O11) who were receiving antihypertensive medications, and those who had hyperlipidaemia (E78.5), who received antihyperlipidaemics during the study period. Data were extracted using SAS® system version 9.4 classification codes. The Kaplan-Meier approach, used to compare the survival experience of patients who commenced treatment for hypertension and hyperlipidaemia, was conducted using IBM® SPSS® version 25. The time to the commencement of treatment of hypertension and hyperlipidaemia among the diabetics were measured in days. With 2008 serving as the index year, we followed up on patients until 31 December 2016. RESULTS AND DISCUSSION: A total of 494 patients with an average age of 53.5 (SD 11.1) years were included in the study, 34.8% of whom were females. Prevalence of hyperlipidaemia and hypertension among patients were 35.0% and 45.6%, respectively. Average time-to-onset of treatment for hyperlipidaemia was 2684.4 (SD 42.2) days compared to 2434.2 (SD 47.6) days for hypertension. There was no statistically significant difference in age and sex among patients who started treatment for either of these conditions during the study (P = 0.404; Cohen's d = 0.132 for hyperlipidaemia and P = 0.644, Cohen's d = 0.059 for hypertension). WHAT IS NEW AND CONCLUSION: Within an average of 6 years after an index period of 1 year free of disease, diabetics may commence treatment for hyperlipidaemia, hypertension or both. With all significant data appropriately captured, medicine claims data can be effectively used in survival analysis to determine time-to-onset of treatment for hyperlipidaemia and hypertension among diabetics.

Public hospital pharmacists' knowledge, attitudes, and practices for antibiotic stewardship implementation in Limpopo Province, South Africa.

BACKGROUND: Hospital pharmacists are important in antibiotic stewardship programs (ASP), a global strategy to combat antibiotic resistance (ABR). South African public hospitals have limited ASP implementation. This study describes Limpopo Provincial Hospital pharmacists' knowledge, attitudes, and practice toward ASP implementation. METHOD: A questionnaire to explore pharmacists' knowledge, attitudes and practices regarding ASP implementation comprised 43 questions hosted online. A link was sent by invitation e-mail to eligible respondents in November 2021. Five questions on respondents' demographics, 15 questions on ASP knowledge, 10 Likert scale questions on attitude, and 13 on ASP practices were included. Mean (standard deviation (SD)) knowledge and attitude scores and a median (interquartile range (IQR)) practice score was calculated. Associations between categorical variables were assessed using chi-square/Fisher's exact analysis (p < 0.05), with Cramér's V as effect size. RESULTS: The survey yielded 35 responses (13.1%). Twenty (57.1%) respondents were female. Seventeen (48.6%) respondents were between the ages of 31 and 40 years. The mean knowledge score of respondents was 9.8 (2.6) (N = 34), with knowledge gaps on One Health and socioeconomic determinates of ABR. Ten (29.6%) respondents thought One Health discouraged multi-sector collaboration, and nineteen (55.9%) respondents thought ASP was the only strategic response to ABR. Sixteen (47.1%) respondents did not know that poor access to clean water accelerates ABR and seventeen (50.0%) did not know that poverty could be a determinant for antibiotic use. The mean respondent attitude score was 8.0 (1.7) (N = 28). Twenty-seven (96.4%) respondents agreed that ASP was necessary and agreed to participate in ASP respectively. All 28 (100.0%) respondents agreed to lead an ASP. The median (IQR) respondents' practice score was - 2.0 (IQR: -6.0-5.8) (N = 16). Respondents were inconsistently (never, sometimes, every time) participating in multi-disciplinary forums (6/16, 37.5%) and expressed a desire for training (11/13, 84.6%) on ASP through in-service (7/27, 25.9%). Respondents thought ASP training should include medical officers (12/29, 41.4%) and nurses (9/29, 31.8%). Knowledge score was associated with gender (p = 0.048; V = 0.416) and attitude score (p = 0.013; V = 0.556). CONCLUSION: Our study found pharmacists had good knowledge and a positive attitude toward ASP implementation but poor ASP practices. A multi-disciplinary in-service training could address identified knowledge and practice gaps.

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.

Antibiotic prescribing to inpatients in Limpopo, South Africa: a multicentre point-prevalence survey.

BACKGROUND: Electronic continuous surveillance databases are ideal for monitoring antibiotic use (ABU) in hospitalised patients for antibiotic stewardship programmes (ASP). However, such databases are scarce in low-resource settings. Point prevalence surveys (PPS) are viable alternatives. This report describes ABU and identifies ASP implementation improvement areas in Limpopo Province, South Africa. METHODS: This cross-sectional descriptive study extracted patient-level ABU data from patients' files using a modified global PPS tool. Data were collected between September and November 2021 at five regional hospitals in Limpopo Province, South Africa. All patients in the wards before 8 a.m. on study days with an antibiotic prescription were included. Antibiotic use was stratified by Anatomic Therapeutic Chemical and Access, Watch, Reserve classifications and presented as frequencies and proportions with 95% confidence intervals (CI). Associations between categorical variables were assessed using the chi-square test. Cramér's V was used to assess the strength of these associations. RESULTS: Of 804 inpatients surveyed, 261 (32.5%) (95% CI 29.2-35.7) were prescribed 416 antibiotics, 137 were female (52.5%) and 198 adults (75.9%). One hundred and twenty-two (46.7%) patients received one antibiotic, 47.5% (124/261) received two, and 5.7% (15/261) received three or more antibiotics. The intensive care units had a higher ABU (68.6%, 35/51) compared to medical (31.3%, 120/384) and surgical (28.5%, 105/369) wards (p = 0.005, Cramér's V = 0.2). Lower respiratory tract infection (27.4%, 104/379), skin and soft tissue infections (SST) (23.5%, 89/379), and obstetrics and gynaecology prophylaxis (14.0%, 53/379) were the common diagnoses for antibiotic prescriptions. The three most prescribed antibiotic classes were imidazoles (21.9%, 91/416), third-generation cephalosporins (20.7%, 86/416) and combination penicillin (18.5%, 79/416). Access antibiotics accounted for 70.2% (292/416) of prescriptions and Watch antibiotics for 29.6% (123/416) (p = 0.110, Cramér's V = 0.1). Reasons for prescribing and treatment plans were documented in 64.9% (270/416) (95% CI 60.3-69.5) and 21.4% (89/416) (95% CI 17.3-25.3) of prescriptions, respectively. CONCLUSIONS: The study serves as a baseline for ABU surveillance at the five regional hospitals in Limpopo Province. Lack of documentation indicates poor prescribing practices; ASP should address gaps by deploying evidence-based, multifaceted and stepwise interventions.

Incidence patterns of childhood cancer in two tertiary hospitals in Ghana from 2015 to 2019: A retrospective observational study.

BACKGROUND: Accurate epidemiological data are vital in estimating the burden of disease in a country. Little is known about the incidence of childhood cancer in Ghana. This study describes the incidence patterns of cancer in children below 14 years and 11 months from 2015 to 2019 at the only two main pediatric cancer referral centers in Ghana: Korle Bu Teaching Hospital (KBTH) and Komfo Anokye Teaching Hospital (KATH). METHOD: Data on the incidence of cancer in children below 14 years and 11 months were collected retrospectively between 1st January 2015 and 31st December 2019 from patients' medical folders at KBTH and the cancer registry at the pediatric units of KATH. Descriptive statistics were used to describe the data. Incident rates expressed as age-specific rates (ASRs) per 100,000 person-years using population estimates for age groups and sex in each year, were determined by age groups (0-4, 5-9, 10-14 years and 11 months), sex, region of residence and cancer types based on the International Childhood Cancer Classification, third edition. RESULTS: The total ASR per 100,000 person-years from 2015 to 2019 was 9.36 based on 1073 cases observed. The ASR increased from 1.6 per 100,000 person-years in 2015-2.41 in 2017, thereafter decreasing to 1.45 in 2019. The ASR was higher in male children (2.10 per 100,000 person-years), children between 0 and 4 years (0.27 per 100,000 person-years), and children living in the Greater Accra region (4.17 per 100,000 person-years). The most prevalent cancers were lymphomas (2.17 per 100,000 person-years) and leukemia (1.88 per 100,000 person-years). CONCLUSION: The study provides baseline information on the incidence patterns of childhood cancer from 2015 to 2019, addressing a critical gap in childhood cancer epidemiology in Ghana.

Antibiotic consumption by Access, Watch and Reserve index in public sector of Limpopo province, South Africa: 2014-2018.

Background: The World Health Organization (WHO) classified antibiotics into three categories in 2017 - Access, Watch and Reserve (AWaRe) - intending to reduce the consumption of Watch and Reserve antibiotics while increasing the use of Access antibiotics. Antibiotic consumption by AWaRe in South Africa is undetermined because of data and research scarcity. Objectives: The aim of this study was to quantify, describe and track antibiotic consumption between 2014 and 2018 in the public sector of the Limpopo province, South Africa, using the WHO's AWaRe classification for 2021. Method: Antibiotic consumption was quantified from pharmaceutical sales data for 2014-2018 by defined daily dose (DDD) per 1000 inhabitants per day (DID) and described according to the AWaRe classification. The change in antibiotic consumption was measured by compound annual growth rate (CAGR), Access-to-Watch index (AW-I), 75% drug utilisation index (DU75%) and amoxicillin index (AI). Results: The absolute consumption of Access antibiotics decreased by a 4.0% CAGR from 3.7 DID in 2014 to 3.0 DID in 2018, with relative consumption remaining above 80.0%. Relative consumption of Watch antibiotics increased by 15.8% CAGR from 7.8% in 2014 to 19.7% by 2018. The AW-I decreased from 10.4 in 2015 to 4.1 in 2018. The AI increased from 17.8% in 2015 to 42.0% in 2018. Parenteral formulations' DU75% comprised one Watch (ceftriaxone) and two Access (metronidazole and benzylpenicillin) antibiotics. Conclusion: In Limpopo province's public sector, the consumption of Watch antibiotics increased, while Access antibiotics consumption decreased, as reflected by both relative consumption and the decrease in the AW-I. The determinants of the Watch antibiotics increase require research attention. Contribution: Our study addressed the paucity of surveillance and research data on antibiotic consumption in the Limpopo province, South Africa, according to the WHO AWaRe classification.

Antibiotic consumption in the public sector of the Limpopo province, South Africa, 2014-2018.

Background: Antibiotic consumption (ABC) surveillance is a critical component of the strategic priority response to the increasing antibiotic resistance threat. Levels of ABC at the national and provincial levels in South Africa are unknown because of inadequate ABC surveillance systems and literature. Antibiotic consumption in the public sector of Limpopo province, South Africa, 2014-2018. Methods: This retrospective study used sales data retrieved from a pharmaceutical warehouse distribution database to quantify ABC. Antibiotic consumption was measured by the defined daily dose (DDD) per 1000 inhabitants per day (DID) and 75% drug utilisation index (DU75%). Change in consumption was measured by the compound annual growth rate (CAGR). Results: Between 2014 and 2018, the mean ABC was 4.6 ± 1.0 DID, with an overall decrease of 1.6% in the CAGR. Penicillins (2.3 ± 0.8; 50.0%), sulphonamide and trimethoprim combinations (1.4 ± 0.3 DID; 30.4%) were the most consumed antibiotics. Macrolides had the highest relative increase in consumption during the study period, with a CAGR of 18.5%. In contrast, tetracyclines had the highest relative decrease in consumption, with a CAGR of 100.0%. The CAGR ratio for broad- to narrow-spectrum increased by 39.3%, from 0.4 in 2014 to 2.1 in 2018. The DU75% comprised amoxicillin (28.4%), sulphamethoxazole and trimethoprim (SMX-TMP) (27.2%), doxycycline (12.3%) and azithromycin (9.2%). Conclusion: While ABC remained relatively stable throughout the study, there was an increase in broad-spectrum ABC that requires further investigation. Contribution: This study contributes ABC surveillance data in Southern Africa, described by ATC classification, which is essential for monitoring and evaluating antibiotic stewardship programmes.

Changes in the incidence and prevalence of human immunodeficiency virus or acquired immunodeficiency syndrome in the South African medical schemes environment: 2005-2015.

BACKGROUND: The South African (SA) private medical schemes environment has over the past two decades respond to the evolving needs of people living with the human immunodeficiency virus (PLWH) or acquired immunodeficiency syndrome (AIDS). OBJECTIVE: To determine changes in the incidence and prevalence rate of human immunodeficiency virus (HIV) or AIDS in the SA private medical schemes environment from 2005 to 2015. METHOD: In this observational study, a single, pharmaceutical benefit management (PBM) company's medicine-claims database of members with HIV or AIDS has been retrospectively analysed from January 2005 to December 2015. The cohort includes all patients identified by the HIV or AIDS-related diagnostic ICD-10 codes, B20-B24, who also claimed antiretroviral medication during that period. RESULTS: From 2005 to 2015, the proportion of HIV or AIDS patients enrolled in the PBM-company increased from 0.63% to 2.10%, and the incidence rate of new cases among the beneficiaries increased 2.3 times. The highest HIV or AIDS prevalence and incidence rates were found in the age group ≥ 40 and < 60 years, followed by the age group ≥ 60 and < 70 years. The highest prevalence rates in 2015 were recorded in Gauteng, namely, 422.4/1000 beneficiaries, followed by Western Cape (149.4/1000), and KwaZulu-Natal (118.4/1000). CONCLUSION: There has been an increase in the number of SA-PLWH accessing treatment in the medical scheme environment. The high prevalence of HIV infection among older members should signal concern that HIV-related comorbid conditions are likely to become a growing component of care required by PLWH utilizing the SA private healthcare sector.

Prospective analysis of the medicine possession ratio of antidepressants in the private health sector of South Africa, 2006 - 2011.

BACKGROUND: Major depressive disorder (MDD) is a disabling mental illness with high morbidity and mortality rates. Inadequate treatment efficacy, unfavourable side-effect profiles and consequent shortfalls in compliance are major stumbling blocks in its treatment. Non-compliance data in low- to middle-income countries are lacking. OBJECTIVE: To investigate the prevalence of antidepressant (AD) non-compliance in the private healthcare sector of South Africa (SA). METHODS: We conducted a prospective cohort study analysing AD medicine claims (N=35 175) for 14 135 patients, obtained from a nationally representative pharmaceutical benefit management company, over a 6-year study period (1 January 2006 - 31 December 2011). The medicine possession ratio (MPR) was used as a proxy to determine compliance with AD medication. Only patients >18 years of age whose treatment had been initiated by a psychiatrist following an appropriate International Classification of Diseases (10th edition) (ICD-10) diagnosis of a mood disorder were included. A patient was considered compliant if the MPR was between ≥80% and ≤110% over a >4-month treatment period. RESULTS: After the first 4 months, only 34% of patients were compliant. A statistically significant association was found between active ingredient consumed and compliance (p<0.0001). Only 26.2% of patients who received amitriptyline-containing products were compliant, compared with 38.8% and 38.7% for venlafaxine and duloxetine, respectively. CONCLUSION: Compliance data collected from pharmacy claims provide a workable estimate of the broader clinical scenario they represent. Although differences between classes of AD were evident, non-compliance was found to be high in the private healthcare environment of SA, comparable with global trends.