1. PHARMACOVIGILANCE AND CLINICAL TRIALS DIVISION 20 August 2015 Victoria Falls Protecting Your Right to Quality Medicines and Medical Devices

2. Activities Of The PVCT Division Pharmacovigilance Activities Regulation Of Clinical Trials Involving Medicines And Medical Devices

3. PHARMACOVIGILANCE Pharmacovigilance: is the science and activities relating to the detection collection assessment monitoring, and prevention of adverse effects related to pharmaceutical products and communication in a way that improves therapeutic outcomes (W.H.O) Protecting Your Right to Quality Medicines and Medical Devices

4. Adverse Drug Reactions (ADRs) Any response to a drug which is noxious and unintended, including lack of efficacy, which occurs at doses normally used for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function Protecting Your Right to Quality Medicines and Medical Devices

6. Spontaneous report ( ICSR - individual case safety report) ‘an unsolicited communication by healthcare professionals or consumers that describes one or more adverse drug reactions in a patient who was given one or more medicinal products and that does not derive from a study or any organised data collection scheme’

7. Targeted spontaneous report ‘a spontaneous report from a healthcare professional or consumer within a defined cohort that describes one or more adverse drug reactions in a patient who was given one or more medicinal products’

8. Importance of reporting generation of “signals” influence drug labelling Documentation of previously unknown ADRs Withdrawal of drugs e.g dextropropoxyphene (Doxypol) Ultimately, improved therapeutic outcomes Protecting Your Right to Quality Medicines and Medical Devices

9. What is a signal? CHALLENGE QUESTION (Adapted from the FDA) A safety “signal” is defined as: A.New, previously unknown, adverse event B.New drug interaction C. An observed increase, either in quantity or severity, of a known adverse event D. All of the above Protecting Your Right to Quality Medicines and Medical Devices

10. Importance of reporting There are differences in ADRs among people from different countries or regions Usually due to differences in diseases and prescribing practices; genetics, diet, traditions of the people; drug manufacturing processes Protecting Your Right to Quality Medicines and Medical Devices

11. Importance of reporting Data derived from within the country or region may have greater relevance and educational value and may encourage national regulatory decision-making. Information obtained in one country (e.g. the country of origin of the drug) may not be relevant to other parts of the world, where circumstances may differ. Protecting Your Right to Quality Medicines and Medical Devices

12. Barriers to ADR Reporting We already know the ADR What benefit is it? Scared to report Failure to recognise ADR All approved medicines are safe notion

13. Barriers to ADR Reporting Not aware of regulations attitude Odd reactions ADRs may mimic a common natural disease Long delay in the appearance of the Adverse effect Disease complexity clouds drug-related issues

14. TSR of anti-TBs and ARVs- Pilot Phase Background: Adverse drug reaction monitoring is essential in achieving the goals of anti-retroviral (ARV) and anti-tuberculosis (anti-TB) treatment, and is an important element in promoting rational medicine use principles and promoting patient safety. Protecting Your Right to Quality Medicines and Medical Devices

15. TSR of anti-TBs and ARVs- Pilot Phase Objectives: The pilot phase of the Targeted Spontaneous Reporting (TSR) system for monitoring adverse drug reactions pilot phase research was carried out to strengthen pharmacovigilance activities in the National ART and TB programmes in Zimbabwe; and to understand and characterize adverse drug reactions (ADR’s) or individual case safety reports (ICSRs) due to ARV and anti-TB medicines. Protecting Your Right to Quality Medicines and Medical Devices

16. TSR of anti-TBs and ARVs- Pilot Phase Results: Age range was 0.9-76 years (median = 38 years) In 83% of the reports, one ADR was reported per patient In 11% of the reports, two ADRs were reported per patient In 6% of the reports, three ADRs were reported per patient Protecting Your Right to Quality Medicines and Medical Devices

17. TSR of anti-TBs and ARVs- Pilot Phase Results: The majority of ADR’s reported were mainly cutaneous in nature Cutaneous (44%) CNS (27%) metabolic in nature (11%) Protecting Your Right to Quality Medicines and Medical Devices

18. TSR of anti-TBs and ARVs- Pilot Phase Results: Efavirenz vs Nevirapine lower odds of cutaneous reactions compared to those on Nevirapine containing regimens (OR=0.07, p-value<0.0005) higher odds of CNS type of reactions compared to those on NVP (OR=6.0; p-value<0.0005). gastrointestinal reactions which were more frequent in those on Efavirenz containing regimens (OR=3.3, p-value=0.03). Protecting Your Right to Quality Medicines and Medical Devices

19. TSR of anti-TBs and ARVs- Pilot Phase Conclusion: Pharmacovigilance activities need to be strengthened and included as part of clinical care especially for patient on ART and anti-TB treatment including essential medicines. Protecting Your Right to Quality Medicines and Medical Devices

20. TSR of anti-TBs and ARVs- Pilot Phase Conclusion: The TSR pilot phase demonstrated significant increase in ADR reporting and considered relatively a feasible cost effective method hence TSR was scaled up to the main phase program. Protecting Your Right to Quality Medicines and Medical Devices

21. TSR of anti-TBs and ARVs- Pilot Phase Conclusion: Further in depth analysis of ICSRs of medicines reported such as tenofovir in combination with other anti-retrovirals is required. Protecting Your Right to Quality Medicines and Medical Devices

22. Resources Drug Information Bulletin (MCAZ website) ADR reporting form (MCAZ website, email, request for hard copies) Product defect reporting form(MCAZ website, email, request for hard copies) TSR protocol Protecting Your Right to Quality Medicines and Medical Devices

24. THANK YOU!!! Protecting Your Right to Quality Medicines and Medical Devices