1. 3. National Tuberculosis and Leprosy Control Program, Abuja, Nigeria
5th International Conference and Exhibition on Pharmaceutical Regulatory Affairs, August 03-05, 2015 Florida, USA
The effectiveness of the spontaneous reporting system at detecting suspected adverse drug reactions in a resource limited setting
Avong YK1, Jatau B1, Ekong E1, Ndembi N1, Okuma J1, Osakwe A2, Akang G3, Agbaje A1, Mensah C1, Dakum P1
1.Institute of Human Virology, Nigeria, Maina Court, Herbert Macaulay Way, Abuja, Nigeria
2. National Agency for Food and Drug Administration and Control (NAFDAC), Abuja
3. National Tuberculosis and Leprosy Control Program, Abuja, Nigeria

2. Introduction
Adverse events (AEs) of second line anti-tuberculosis drugs (SLDs) are relatively well documented. However, the actual burden has rarely been described in detail in programmatic settings
The spontaneous reporting system (SRS) was utilized to investigate the occurrence of these events in the national cohort of multidrug-resistant tuberculosis (MDR-TB) patients in Nigeria

3. Aims and objectives
The aim was to investigate the burden of ADRs as well as assess some of the risk factors during the intensive phase of MDR-TB treatment. The objectives were to measure:
The incidence of ADRs
The types and severity of ADRs
Time to onset of ADRs
Duration of ADRs

4. Study Sites

5. Methods
Design:
A retrospective, multicenter observational cohort study, using pharmacovigilance data systematically collected at all MDR-TB treatment centers in Nigeria
Characteristics of AEs during the intensive phase treatment were documented, and risk factors for development of AEs were assessed

6. Statistics
Summary statistics applied to describe socio-demographic and treatment characteristics
Associations between the occurrence of AE and demographic and clinical characteristics were explored through multivariate logistic regression using a stepwise backward elimination approach
P-values based on Wald’s test are indicated

7. Measurement tool
The NAFDAC “Yellow form” was used as the primary tool for data collection
The Yellow form has 4 main sections:
1. Patient details
2. Adverse drug reaction
3. Suspected drug and
4. Source of report

8. NAFDAC Yellow Form Patient Details Section
Adverse Drug Reaction Section
Suspected Drug Section
Source of Report Section

9. Result: ADR reporting rate
VARIABLE
NUMBER (%)
TOTAL
460
Mainland Hospital, Yaba, Lagos
97 (21)
Government Chest Hospital, Jericho
82 (18)
University College Hospital, Ibadan
69 (15)
National Tuberculosis and Leprosy Training Center, Zaria
41 (9)
Infectious Disease Hospital, Kano
40 (9)
University of Port Harcourt Teaching Hospital, Port Harcourt
38 (8)
Jos University Teaching Hospital, Jos
29 (6)
University of Uyo Teaching Hospital, Uyo
13 (3)

10. Result: Characteristics

11. Burden and Severity of ADRs
Total fatality= 4 [GI= 2; Electrolyte imbalance =1; Heart Failure = 1; Burden: GI, Neurological, Ototoxicity, Psychiatric; Debility: Ototoxicity, Psychiatric

12. Time to Onset of ADR
Allergic reactions (median time) = 20 days; Electrolyte imbalance (median time) = 174 days. Implications: Patients monitoring must continue as long as the patient is on therapy.

13. Duration of ADRs
Most ADR resolved after a median of 13 days. Implication: Do not rush to discontinue therapy at the appearance of ADRs as most will resolve. Adherence should however be enforced so that patients do not drop out of the program.

14. ADRs and risk factors Body weight increased the risk of ADRs
HIV did not expose the patients to greater risk of ADRs
Age was not associated with ADRs

15. Discussion
We reported a wide range of ADRs, thereby confirming existing knowledge on the toxicity of SLDS and the effectiveness of the SRS. ADRs should be managed concurrently with MDRTB
The most frequently occurring ADRs: Gastro-intestinal condition, especially bleeding; Neurological conditions, Ototoxicity and psychiatric disorders. Health workers should be alert to these ADRs
Fatality was associated with GIT bleeding, electrolyte imbalance and heart failure. Prompt treatment needed
Disability was associated with ototoxicity and psychiatric disorders. Hearing aids needed

16. Discussion
Allergic reactions (mainly allergy) were the first to occur, while electrolyte imbalance took longer time to occur. Patient monitoring should commence early and should continue until therapy is completed with full cure
Most ADRs resolved after a relatively short period. Do not rush to discontinue therapy at the appearance of ADRs but adherence should be enforced at this time
Increased in body weight increased the risk of ADRs. This is unusual; overdosing is however suspected.
Age had no association with ADRs. This might be cohort specific as mean age was only 33 years.

17. Discussion
Significant variation in the reporting of ADRs by treatment centers. Standardization of training of all health workers is needed
Co-infection with HIV did not significantly increased the risk of ADRs. Treatment of MDRTB should not be delayed because of HIV

18. Conclusion
The SRS unmasked a wide range of AEs among the participants, some of which were disabling and fatal
Early identification and prompt management as well as standardized reporting of AEs at all levels of healthcare, including the community is urgently needed.
Safer regimens for drug-resistant TB with the shortest duration are advocated
The SRS was reliable and could be used in public health programs like the anti-retroviral therapy, MDRTB and malaria

19. Limitations Misclassification of ADRs
Chronic ADRs may not have been captured

20. Acknowledgements Institute of Human Virology, Nigeria
National Tuberculosis and Leprosy Control Program, Nigeria
National Agency for Food and Drug Administration and Control
Global Fund to Fight AIDS, Tuberculosis and Malaria
Research and Training in Tropical Diseases at the World Health Organization (WHO/TDR)
WHO Regional Office for Europe, Operational Research Unit (LUXOR)
 Médecins Sans Frontières, and Brussels Operational Center, Luxembourg;
 The Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, France
Study participants and staff of study sites