Experiences and Lessons From Implementing Cohort Event Monitoring Programmes for Antimalarials in Four African Countries: Results of a Questionnaire-Based Survey.

INTRODUCTION: Cohort event monitoring (CEM) is an intensive method of post-marketing surveillance for medicines safety. The method is based on prescription event monitoring, which began in the 1970s, and has since been adapted by WHO for monitoring the safety of medicines used in Public Health Programmes. CEM aims to capture all adverse events that occur in a defined group of patients after starting treatment with a specific medicine during the course of routine clinical practice. OBJECTIVE: The aims of this study were to describe the experiences of National Pharmacovigilance Centres (NCs) that have used CEM to monitor artemisinin-based combination therapy (ACT) for uncomplicated malaria in the African setting, to raise awareness of some of the challenges encountered during implementation and to highlight aspects of the method that require further consideration. METHOD: A questionnaire-based survey was conducted to capture the experiences of NCs that have implemented CEM for active post-marketing surveillance of antimalarial medicines in sub-Saharan Africa. Six NCs were identified as having implemented CEM programmes and were invited to participate in the survey; five NCs indicated willingness to participate and were sent the questionnaire to complete. RESULTS: Four NCs responded to the survey-Ghana, Kenya, Nigeria and Zimbabwe-providing information on the implementation of a total of six CEM programmes. Their experiences indicate that CEM has helped to build pharmacovigilance capacity within the participating NCs and at the monitoring sites, and that healthcare providers (HCPs) are generally willing to participate in implementing the CEM method. All of the programmes took longer than expected to complete: contributing factors included a prolonged enrolment period and unexpectedly slow data entry. All of the programmes exceeded their budget by 11.1-63.2 %. Data management was identified as a challenge for all participating NCs. CONCLUSIONS: The reported experiences of four NCs that have undertaken CEM studies on ACTs indicate that CEM has helped to build pharmacovigilance capacity within NCs and monitoring sites and that HCPs are willing to participate in CEM programmes; however, the method was found to be labour intensive and data management was identified as a challenge. Reducing the workload associated with CEM, particularly in relation to data management, and integrating the method into the routine work of HCPs and NCs should be considered for future implementation.

Safety of Artemisinin-Based Combination Therapies in Nigeria: A Cohort Event Monitoring Study.

BACKGROUND: A pilot programme of Cohort Event Monitoring (CEM) was conducted across the six geopolitical zones of Nigeria on patients treated for uncomplicated malaria with artemisinin-based combination therapy (ACT). The emergence and spread of malaria parasites resistant to commonly available antimalarial drugs necessitated a shift in policy for malaria treatment by the Federal Government from the use of chloroquine and sulphadoxine-pyrimethamine (SP) as first-line treatments to ACTs. Initial reports following deployment of ACTs in clinical settings raised safety concerns regarding their use. Although artemisinin and its derivatives are generally thought to be safe, there are currently few or no data on their safety among populations in Nigeria. OBJECTIVES: The main objectives of the CEM programme were to proactively determine the adverse event (AE) profile of artesunate/amodiaquine (AA) and artemether/lumefantrine (AL) in real-life settings and to find out the factors predisposing to AEs. METHODS: The CEM study was observational, longitudinal, prospective, and inceptional. Patients were observed in real-life situations. It was conducted in six public health facilities in Nigeria on patients with a clinical diagnosis of uncomplicated malaria treated with ACTs. Patients were prescribed one of the ACTs on an alternate basis as they enrolled into the programme. Follow-up reviews were undertaken on days 3 and 7 following commencement of ACT treatment. At follow-up, patients were evaluated for any clinical event that they might have experienced following the use of the ACTs. We report the result of this initial pilot in which 3,010 patients treated for uncomplicated malaria with AA or AL were enrolled. RESULTS: The seven most common AEs seen were general body weakness 25.0/36.6% (AL/AA); dizziness 11.9/17.2% (AL/AA); vomiting 8.0/10.2% (AL/AA); abdominal pain 8.5/7.2% (AL/AA); insomnia 6.3/5.9% (AL/AA); body pains 3.4/5.2 (AL/AA) %; anorexia 8.5/4.6% (AL/AA). Most adverse events occurred from day 1 and peaked by day 2 and 3 of medication with the mean duration of events being 3 days. By the end of the follow-up visit on day 7, the AEs had resolved in the majority of patients. Adverse events were more common in the AA group than AL revealing a better safety profile for AL (p < 0.001). Both ACTs demonstrated good ability to resolve the clinical symptoms of uncomplicated malaria. CONCLUSION: In conclusion, this pilot CEM programme suggests that adverse events with ACTs were common. However, serious life-threatening events were not common. It appears that ACTs have a tolerable safety profile among Nigerians.