cohort event monitoring (cem) study of acts in nigeria dr peter u. bassi principal investigator (pi)...

COHORT EVENT MONITORING (CEM) STUDY OF ACTs IN NIGERIA

Dr Peter U. BassiPrincipal Investigator (PI)

Nigeria Study Group

Antalya - Turkey14th – 18th November 2011

21/04/23 1 ACTs PILOT STUDY IN NIGERIADR BASSI

INTRODUCTION

21/04/23 3 ACTs PILOT STUDY IN NIGERIADR BASSI

• 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

OBJECTIVES

21/04/23 DR BASSI 4 ACTs PILOT STUDY IN NIGERIA

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)

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

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.

DESIGNThe 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.

METHODOLOGY

Ibadan

Zaria Gombe

EnuguUyo

The study sites

FCT

Map of Nigeria showing the CEM study sites

SITES: 6 sentinel sites spread across the 6 geopolitical zones of the country as shown on map

7 ACTs PILOT STUDY IN NIGERIADR BASSI 21/04/23

METHODOLOGY


POPULATIONA 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 PERMISSIONAdvocacy 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).

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.

RESULTS


General statistics


S/no Data Element Total %1 Total number of patients enrolled 3010 1002 Total number who return at 1st FUV 2904 96.5

3 Total number who return at the 2nd FUV only 59 2.0

4 Total number patients follow-up(2+3) 2963 97.5

5 Total number of patients who are lost to follow up

47 1.6

Distribution of cohort by age and sex


Pattern of symptoms at presentation


Distribution of Co-Morbid Conditions


Frequency of New Events at 1st Follow Up Visit (FUV)


ABDPAIN, 135

LOSS OF APPETITE, 49

BODY PAIN, 48BITTERNESS OF

MOUTH, 4CHILLS/RIGOUR

, 1

COUGH, 6

DIARRHEA, 29DIZZYNESS, 180

FEVER, 22

HEAD ACHE, 50JOINT PAIN, 7NAUSEA, 32

VOMITTING, 104

WEAKNESS, 424

Distribution of new events by drug use at 1st FUV


New /worsening (Persisting) events at 2nd FUV


0

20

40

60

80

100

120

Malaria Treatment outcome


0

10

20

30

40

50

60

70

%AA

%AL

Treatment Outcome of New Events


0

100

200

300

400

500

600

Recovered Improved Remain Unchanged

Life threatening

Prolong Hosp. stay

551

303

110

2 1

139

5421

0 1

AAAL

Infrequent but important adverse events (1st &2nd FUV)


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

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.


• 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

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.

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

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

25

“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

THANK YOU FOR LISTENING

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- ABUJA4. SOCIETY FOR FAMILY HEALTH, ABUJA-NIGERIA5. YAKUBU GOWON CENTRE, NIGERIA

cohort event monitoring (cem) study of acts in nigeria dr peter u. bassi principal investigator (pi)...

Documents

use of acts

nigeriadr bassi cem

map7 acts pilot study

safety profile of acts

dr bassi data collection

designthe study

standard course of acts

cem study sitessites