Pharmacovigilance of suspected or confirmed therapeutic ineffectiveness of artemisinin-based combination therapy: extent, associated factors, challenges and solutions to reporting.

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.