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IntroductionCombination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).Pharmacovigilance—monitoring the effects of medicines—is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.The Med Safety mobile application has been developed through the European Union’s Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda’s National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown.Methods and analysisA pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only.Ethics and disseminationEthical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia.Trial registration numberPACTR202009822379650.

IntroductionPatients have contributed Methods and analysisThis is a quasi-experimental study to be implemented over 4 months at 12 intervention and 12 comparison cART sites from four geographical regions of Uganda. Per region, two blocks each with a tertiary, secondary and primary care cART site will be selected by simple random sampling. Blocks per region will be randomly assigned to intervention and comparison arms.Study units will include cART sites and PLHIV receiving cART. PLHIV at intervention sites will be assigned to peer supporters to empower them to report ADRs directly to the National Pharmacovigilance Centre (NPC). Peer supporters will be expert clients from among PLHIV and/or recognised community health workers.Direct patient reporting of ADRs to NPC will leverage the Med Safety App and toll-free unstructured supplementary service data interface to augment traditional pharmacovigilance methods.The primary outcomes are attrition rate measured by number of study participants who remain in the study until the end of follow-up at 4 months; and number of ADR reports submitted to NPC by PLHIV as measured by questionnaire and data abstraction from the national pharmacovigilance database at baseline and 4 months.Ethics and disseminationThe study received ethical approval from: School of Health Sciences Research and Ethics Committee at Makerere University (MAKSHSREC-2020-64) and Uganda National Council for Science and Technology (HS1206ES). Results will be shared with PLHIV, policy-makers, the public and academia.Trial registration numberISRCTN75989485.

WHAT IS KNOWN AND OBJECTIVE The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) methodology is a WHO gold standard for ensuring systematic Drug Utilization Research (DUR) and has been mainly used in the developed world. This article examines the challenges and way forward for using this methodology in resource-limited countries. CONTENT The ATC/DDD is superior over other methods employed in DUR as it offers a unified medicines regulation and management system at all care levels. The ATC/DDD allows access to standardized and validated information on DUR by: assessing patterns of utilization, defining optimal use levels, identification of gaps, aggregating and analysing statistics for reporting adverse drug reactions, as well as assisting in developing rational medicines use interventions and monitoring their outcomes. WHAT IS NEW AND CONCLUSION Application of the ATC/DDD methodology is crucial for improved patient management, optimal consumption of national pharmaceutical budgets and policy formulation in resource-limited countries.

Background Therapeutic ineffectiveness of artemisinin-based combination therapy (ACT) increases the risk of malaria-related morbidity and mortality, and raises healthcare costs. Yet, little has been done to promote the pharmacovigilance (PV) of ACT ineffectiveness in sub-Saharan Africa, particularly in Uganda. This study aimed to determine the extent and associated factors of the past 6 months reporting of suspected or confirmed ACT therapeutic ineffectiveness by healthcare professionals (HCPs), and difficulties and potential solutions to the PV of ACT therapeutic ineffectiveness. Methods Survey of 685 HCPs conducted using a self-administered questionnaire from June to July 2018 in a nationally representative sample of public and private health facilities in Uganda. HCPs disclosed if they had spontaneously reported ACT therapeutic ineffectiveness to appropriate authorities in the previous 6 months. Multivariable logistic regression models were used to identify determinants of past 6-months, HCP-reported ACT therapeutic ineffectiveness. Results One in five (20%, 137/685; 95% CI 17–23%) HCPs reported ACT therapeutic ineffectiveness to an appropriate authority in the previous 6 months. HCPs commonly reported ACT therapeutic ineffectiveness to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever submitted a written report of ACT therapeutic ineffectiveness to Uganda’s National Pharmacovigilance Centre. Common difficulties of reporting ACT therapeutic ineffectiveness were: unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT therapeutic ineffectiveness in the past 6 months were: hospital-status (vs other; OR = 2.4, 95% CI 1.41–4.21), HCPs aged under 25 years (OR = 2.2, 95% CI 1.29–3.76), suspicion of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.3, 95% CI 1.29–3.92), receipt of patient-complaint(s) of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.9, 95% CI 1.62–5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI 0.28–0.93) and western (vs central; OR = 0.4, 95% CI 0.17–0.77) parts of Uganda. Conclusion One in five HCPs reported ACT therapeutic ineffectiveness, mostly verbally to supervisors. The existing adverse drug reaction (ADR)-reporting infrastructure could be leveraged to promote the PV of ACT therapeutic ineffectiveness.

Background: In Uganda, national tuberculosis (TB) treatment guidelines were revised to include the newer generation fluoroquinolones among the second-line treatment options for multidrug-resistant TB. This study was designed to analyze if the prescription of these quinolones is compliant with country recommendations. Methods: This was an observational retrospective study of consumption data for 2017 and 2018 across four selected regional referral hospitals. The sources of consumption data were hospital pharmacy stock cards and the dispensing register. The medical files of patients who had been prescribed fluoroquinolones were also assessed to study compliance with the Uganda Clinical Guidelines and the British National Formulary (BNF). Results: None of the 371 levofloxacin prescriptions analyzed complied with the Uganda Clinical Guidelines, although 250 (67.3%) were prescribed for indications included in the BNF. According to WHO prescription indicators, only 220 (59.3%) prescriptions were appropriate. Conclusion: The prescription of levofloxacin and moxifloxacin increased in the hospitals studied, but in a high proportion of cases, they were not compliant with country recommendations. The findings call for the strengthening of national antimicrobial stewardship programs.

Developing countries can improve their pharmacovigilance systems by analysing their own medication safety data. The aims of this study were to characterize Uganda’s reported adverse drug reaction (ADR) onsets in 2012–2015 that were registered on VigiBase® by 31 December 2017, to document delays in international visibility and the influence of covariates on this delay from ADR onsets in 2013 + 2014, to examine data quality, and to illustrate analytical approaches for safety data, particularly for patients receiving antiretroviral therapy (ART). International delay was defined as elapsed time from complete ADR onset date to entry date on VigiBase®, with covariates examined using Cox proportional hazards regression. Simple random sampling was used to locate the paper-based ADR forms for data quality assurance. Disproportionality for signal detection focused on serious singleton ADR onsets in patients receiving ART. Uganda’s VigiBase® had 1018 patient entries with complete ADR onset dates: 260 in 2012, 293 in 2013, 305 in 2014 and 160 in 2015. Only 16% (154/953) of ADR onsets in 2012–2015 were in patients aged

Introduction Uganda has rapidly increased access to antimalarial medicines in an effort to address the huge malaria disease burden. Pharmacovigilance information is important to guide policy decisions. Objectives The purpose of this study was to establish the burden of adverse drug reactions (ADRs) and associated risk factors for developing ADRs to artemisinin-based antimalarial treatment in Uganda. Methods An active follow-up study was conducted between April and July 2017 in a cohort of patients receiving treatment for uncomplicated malaria in the Iganga, Mayuge, and Kampala districts. Results A total of 782 patients with a median age of 22 years (58.6% females) were recruited into this study, with the majority recruited from public health facilities (97%). Diagnostic tests before treatment were performed for 76% of patients, and 97% of patients received artemether/lumefantrine. The prevalence of ADRs was 22.5% (176/782); however, the total number of ADRs was 245 since some patients reported more than one ADR. The most commonly reported reactions were general body weakness (24%), headache (13%), and dizziness (11%). Women were more likely to develop an ADR (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.1–2.9), urban dwellers were more likely to develop an ADR than rural residents (aOR 9.9, 95% CI 5.4–17.9), and patients with comorbidities were more likely to develop an ADR than those without (aOR 7.4, 95% CI 4.4–12.3). Conclusion The burden of ADRs is high among women and in patients from urban settings and those with comorbidities. Such risk factors need to be considered in order to optimise therapy. Close monitoring of ADRs is key in implementation of the malaria treatment policy. Electronic supplementary material The online version of this article (10.1007/s40264-018-0659-x) contains supplementary material, which is available to authorized users.

Introduction: Ceftriaxone is a third generation cephalosporin recommended as first line treatment option for a number of diseases in Uganda. However, the National Drug Authority has in the recent past received complaints of suspected treatment failure from clinicians who use different brands of ceftriaxone in Uganda. The main aim of the study was to document the treatment outcome following use of ceftriaxone and evaluating the use of ceftriaxone against the current treatment guidelines in Uganda. Methods: A descriptive observational, non-intervention study design to document treatment outcomes after administration of Ceftriaxone injection in hospitalized patients was undertaken in Mubende. A total of 100 hospitalized patients treated with ceftriaxone were enrolled. Results: Overall, Ceftriaxone was used to treat pneumonia in the paediatric ward, presumptive therapy for infection following caesarean section (n=47) and PID in the post-natal ward, while on surgical and medical wards, Ceftriaxone was used to manage upper respiratory infection, bacterial infections and meningitis. There were no Adverse Events reported to have occurred during treatment with ceftriaxone. Of the patients treated with ceftriaxone 18% completed their doses and had regular administration. Majority 60% of the patients had irregular administration with completed doses and 22% did not complete their doses. Conclusion: There is low treatment outcome during use of Ceftriaxone and the empirically treatment is highly prevalent in the hospital. There is high number of inappropriate drug administration, in which patients usually miss doses or do not complete as prescribed. This practice has an effect of affecting the patient outcomes and aggravating antimicrobial resistance. Choice of ceftriaxone use is not guided by culture and sensitivity due to lack of inadequate laboratory infrastructure.

Introduction Developing countries can improve their pharmacovigilance systems by analysing their own medication safety data. Objective The aims of this study were to characterize Uganda’s reported adverse drug reaction (ADR) onsets in 2012–2015 that were registered on VigiBase® by 31 December 2017, to document delays in international visibility and the influence of covariates on this delay from ADR onsets in 2013 + 2014, to examine data quality, and to illustrate analytical approaches for safety data, particularly for patients receiving antiretroviral therapy (ART). Methods International delay was defined as elapsed time from complete ADR onset date to entry date on VigiBase®, with covariates examined using Cox proportional hazards regression. Simple random sampling was used to locate the paper-based ADR forms for data quality assurance. Disproportionality for signal detection focused on serious singleton ADR onsets in patients receiving ART. Results Uganda’s VigiBase® had 1018 patient entries with complete ADR onset dates: 260 in 2012, 293 in 2013, 305 in 2014 and 160 in 2015. Only 16% (154/953) of ADR onsets in 2012–2015 were in patients aged

BackgroundDrug regulatory authorities promote patient safety by, among other ways, monitoring adverse drug events (ADEs). Reporting of ADEs in Uganda is below the average for a well-performing system. Enhancing patients’ understanding of and involving them in reporting ADEs improves drug safety and treatment outcome monitoring. The objective of this study was to describe the knowledge, attitude, and practice of patients and healthcare workers regarding ADEs and ADEs reporting.MethodsA cross-sectional survey was carried out among 1034 respondents from randomly selected households and 327 health workers at health facilities in the Iganga Mayuge Health and Demographic Surveillance Site (IMHDSS). The IMHDSS, located in Uganda, covers 90,000 people living in 17,000 households.ResultsOver half of respondents (59%) sought treatment from private drug shops, 37% from either clinic, health center or hospital, while 4% sought treatment from herbalists, friends or relatives. Over half (56%) were aware of ADEs, 57% expressed willingness to report an ADE while 43% did not know what to do when it occurs. Almost half (46%) could not differentiate between an ADE and the symptoms, and for those who could, the majority (76%) were willing to report it. Only 34% had ever reported an ADE when it occurred to them. Of those who reported, 43% had their drugs changed, 31% were only counseled while 11.5% continued taking the same medication. Among healthcare workers, 95% knew about ADEs, but only 35% had ever reported. Reasons for not reporting were: fear of being victimised or sued (35%); lack of adequate knowledge about ADE (26%); 20% thought it would disappear shortly; and 14% did not find it necessary to report.ConclusionPatients seek their treatment from private providers. Patients want to report ADEs, but they do not have adequate knowledge. Healthcare workers’ reasons for not reporting are subjective. Dedicated pharmacovigilance-related interventions at community level would improve community members’ knowledge and hence ADE reporting rate.

Background Although the national HIV control programme in Uganda has a well-established system for monitoring disease progression and treatment outcomes, monitoring of adverse drug reactions (ADRs) is inadequate. In order to address under-reporting of ADRs, the National Pharmacovigilance Centre, in collaboration with the HIV control programme, piloted a targeted spontaneous reporting (TSR) system as a complementary method to traditional spontaneous reporting. Methods From April 2012 to March 2014, all cases of suspected renal toxicity in 10,225 patients on tenofovir-based regimens were monitored in the regional pharmacovigilance centres of Masaka and Mbale. The identification of renal toxicity was performed using serum creatinine, urinalysis, and other signs and symptoms of kidney injury. Results There was one suspected renal toxicity reported for every 200 patients on a tenofovir-based regimen. Some of the serious reactions reported were death in two cases and bone demineralisation in five patients. Most of patients had been on treatment for 2 years. Those that had been on tenofovir for more than 4 years had raised serum creatinine levels, emphasising the importance of monitoring for the risk of renal damage for longer. We also found that the reporting rate of suspected ADRs for all medicines in the two sites increased almost fivefold during the implementation period. Conclusion Although the occurrence of suspected tenofovir renal toxicity of HIV patients is low, there is need to monitor those at risk so as to prevent irreversible kidney injury. TSR can complement spontaneous reporting for collecting safety data on particular drugs and increase ADR reporting rates. Electronic supplementary material The online version of this article (doi:10.1007/s40264-015-0277-9) contains supplementary material, which is available to authorized users.