COHORT EVENT MONITORING (CEM) STUDY OF ACTs IN NIGERIA

1. COHORT EVENT MONITORING (CEM) STUDY OF ACTs IN NIGERIA Dr Peter U. Bassi Principal Investigator (PI) Nigeria Study Group Antalya - Turkey 14th – 18th November 2011 DR BASSI

2. INTRODUCTION • CEM of ACTs became necessary in Nigeria due to: • Endemic nature of malaria • 63% of diseases in healthcare facilities • 25% of infant mortality • 30% of childhood mortality • 11% of maternal deaths • Reduced efficacy of previously used antimalarials (CQ, SP) • Shift in malaria treatment policy from use of CQ, SP and Artemisinin mono-therapies to ACTs • Change of status of ACTs from POM to OTC medicines • Large scale deployment of ACTs • Inadequate safety data on ACTs in Nigerian population • Inability of SR to adequately capture safety data DR BASSI

3. OBJECTIVES • OVERALL • To evaluate safety in the use of ACTs among populations in Nigeria and develop the safety profile of ACTs used in Nigeria mainly; • Artemeter -Lumefantrine (AL) • Artesunate-Amodiaquine (AA) DR BASSI

4. SPECIFIC OBJECTIVES • Obtain information on adverse events in ACT users • Establish causality relationship between observed adverse events and use of ACTs • Identify risk factors among populations and provide evidence for intervention • Early characterization of Adverse Events(AEs) profile of ACTs • Generate data for decision making • Obtain cohort for future studies DR BASSI

5. METHODOLOGY A pilot of a cohort event monitoring (CEM) programme evaluate and document AEs that could result from the use of two combinations of artemisinin derivatives: AL and AA approved by FMoH for treatment of uncomplicated malaria in Nigeria. DESIGN The study was prospective and observational with patients being observed under real life conditions. Patients were given a standard course of ACTs to be taken over three days and were asked to return for follow-up assessment on days three and seven after commencement of treatment. Patients who did not return were followed up at home or contacted by telephone. DR BASSI

6. METHODOLOGY SITES: 6 sentinel sites spread across the 6 geopolitical zones of the country as shown on map Zaria Gombe Ibadan FCT The study sites Enugu Uyo Map of Nigeria showing the CEM study sites 7 ACTs PILOT STUDY IN NIGERIA 21/10/2014 DR BASSI

7. METHODOLOGY POPULATION A cohort of 3000 was achieved by enrolment of patients treated with either AA or AL until 500 patients were obtained at each site. Patients presumptively diagnosed with malaria and given ACTs were enrolled consecutively irrespective of age, sex, presence of other disease conditions and use of other medicines. Enrolment of patients was performed by trained personnel at each facility from January – April 2009. Patients were given AA or AL according to local clinical practice without pre-allocation of respective numbers. ADVOCACY and PERMISSION Advocacy visits were undertaken to various stakeholder groups including the Federal Ministry of Health and heads of the relevant health institutions. Ethical clearance was obtained from the National Health Research Ethics Committee (NHREC). DR BASSI

8. Data Collection and analysis Any AEs reported by patients on questioning were recorded by trained personnel using specially designed pre- and post-treatment questionnaires They were asked to record only new events since the commencement of treatment or previously existing events that had become worse. The WHO definition of adverse events was used: Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment. Statistical analyses were carried out using simple frequency distribution, percentages, and Chi Square analysis to study relationships. Graphs and tables were employed to present the results. We subjected some potential risk factors for adverse events e.g. age, drug dosage, regimen, gender, pregnancy, use of traditional medications and presence of comorbid conditions (eg respiratory tract infections, epilepsy, diabetes, HIV, diarrhea) to statistical analysis using multinomial logistic regression. 8 ACTs PILOT STUDY IN NIGERIA 21/10/2014 DR BASSI

9. RESULTS DR BASSI

10. General statistics 10 ACTs PILOT STUDY IN NIGERIA 21/10/2014 DR BASSI

11. Distribution of cohort by age and sex DR BASSI

12. Pattern of symptoms at presentation DR BASSI

13. Distribution of Co-Morbid Conditions DR BASSI

14. Frequency of New Events at 1st Follow Up Visit (FUV) DR BASSI

15. Distribution of new events by drug use at 1st FUV DR BASSI

16. New /worsening (Persisting) events at 2nd FUV DR BASSI

17. Malaria Treatment outcome DR BASSI

18. Treatment Outcome of New Events DR BASSI

19. Infrequent but important adverse events (1st &2nd FUV) DR BASSI

20. Summary • Good response rate (97.5%) was recorded • Adherence to study protocol was good (> 63%) • Most sites reached their recruitment target of 500 patients at end of the study • Observed AEs similar to ADR profile of ACTs reported in literature with few documented rare AE such as …. (please provide from data) also observed DR BASSI

21. Summary • Most common Adverse Events (AEs) observed in the Cohort are • General body weakness - 38/36 % (AA/AL) • dizziness - 16.2/1.4% (AA/AL) • Loss of appetite - 9.1/3.5 % ( AA/AL) • Vomiting - 7/5% (AA/AL), • Abdominal Pain - 6.1/1.0% (AA/AL) • Mean Duration of illness (events) is 3days. 21/10/2014 DR BASSI 21 ACTs PILOT STUDY IN NIGERIA

22. Patients treated with AA had more AEs but had better treatment outcome • 2 patients on AA had life threatening AEs • 1 patient each on AA and AL experienced prolonged hospital stay • Twitching/foaming also occurred with use of AA DR BASSI

23. LIMITATIONS/CHALLENGES • Physician splitting the dose of AA and the effect it had on the study findings • Empty fields especially in patients with no complaints - • no data collected on events experienced 7 days before treatment initiation visit thus making it not possible to make comparisons • The relatedness of the AE and use of drug was not done i.e no causality assessment done so far. DR BASSI

24. CONCLUSIONS • CEM help in identifying AEs following use of ACTs and are common reason for treatment interruptions in malaria treatment in Nigeria • The study suggest that ACTs are effective as evidence by> 90% treatment outcome • Severe Adverse events were not common occurrence in the observed cohort • A larger cohort will be helpful to establish statistical significance of findings and probably identify rare AEs. • CEM is a useful tool for identifying AEs especially used in combination with spontaneous reporting of ADRs 21/10/2014 DR BASSI 24 ACTs PILOT STUDY IN NIGERIA

25. WHY CEM AFTER ALLTHIS? “Every system is perfectly designed to produce precisely the results that it gives” Paul Bataldan and Donald Berwick, Institute of Health Care Improvement, Boston c1997 “Medicine used to be simple, ineffective and relatively safe. Now it is complex, effective and potentially dangerous” Cyril Chantler, “The role and education of doctors in the delivery of health care” Lancet 1999

26. THANK YOU FOR LISTENING

27. Acknowledgements 1. Dept. of Medicines Policy and Standard Quality Assurances and safety Medicines ,WHO - Geneva ,Switzerland Mary Couper - David Coulter - Shanthi Pal -Magnus Wallberg 2. NPC, NAFDAC - NIGERIA 3. NATIONAL MALARIA CONTROL PROGRAMME, FMH- ABUJA 4. SOCIETY FOR FAMILY HEALTH, ABUJA-NIGERIA 5. YAKUBU GOWON CENTRE, NIGERIA