TARGETED SPONTANEOUS REPORTING FOR ADVERSE EVENTS RELATED TO ARV:

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1 TARGETED SPONTANEOUS REPORTING FOR ADVERSE EVENTS RELATED TO ARV: PRELIMINARY RESULTS FROM VIETNAM Nguyen Hoang Anh, Nguyen Thi Thuy Van, Le Thi Huong, Masaya Kato, Tran Ngan Ha Technical review meeting of country experiences in ARV toxicity surveillance: sharing preliminary results and lessons learnt, identifying solutions Geneva, 7-8 th November 2013

2 Viet Nam HIV Overview Epidemic: Concentrated epidemic Population (2013): 90 million Estimated HIV population (2012): 256,845 HIV prevalence - age15-49 (2012): 0.46% HIV prevalence PWID (2012): 11.6% Response Harm reduction (NSP, OST), Condom People on methadone maintenance (2012): 12,253 ART rapid scale-up People on ART (2012): 72,711 ART coverage among the eligible (2012): 62% Data sources: General Statistic Office (population), VAAC/MOH (others)

3 NATIONAL GUIDELINE FOR HIV/AIDS DIAGNOSIS & TREATMENT Switch from AZT/d4T + 3TC + NVP to TDF + 3TC + EFV/NVP

4 PHARMACOVIGILANCE PRACTICE IN VIETNAM 1999: became full member of WHO-UMC 1994: Foundation of the 1 st ADR center 2009: Foundation of The National DI & ADR Center Achievements Control of drug quality problems Establishment of spontaneous ADR reporting system by healthcare workers Issued a number of legal documents relating to ADR monitoring

5 Strengthening the national PV system to support PHPs PV SYSTEM National level Regional level effective linkages GOAL Develop a national PV system that effectively links with and supports PHP s practice ensuring drug safety PHP s SYSTEM National level Regional level Healthcare facilities Province & district level Patients Patients

6 PHARMACOVIGILANCE PRACTICE IN HIV/AIDS PROGRAM: CURRENT SITUATION Expansion of ART: 72,711 patients in 2012 Limited information on adverse events of ARV Inadequate training and limited experiences on ARV toxicity monitoring. Frequent change/revision on treatment guidelines

7 COLLECTING SAFETY DATA RELATED TO ARV Spontaneous reporting (SR) Launched in 1994 and mandated by law since 2005 for healthcare professionals Number of spontaneous reports related to ARV received by the National PV Center N o of ARV reports Total reports received % 0,88 0,46 0,49

8 COLLECTING SAFETY DATA RELATED TO ARV Cohort event monitoring (CEM) Pilot of active surveillance on ARV from 10/2011 to 6/2013 at 5 sentinel sites Key findings 645 patients; male 60.2%; age: 34.2 ± 7.9, mean of follow-up: 11,4 months 49,1% patients experienced with ADRs Most common reported ADRs: liver/biliary, skin, CNS, hematology disorders ADR-induced regimen switching: 14.6% Risk factors for ADR identified: d4t-based regimen and liver disorders AZT-based regimen and anemia; NVP-based regimen, CD4 count and skin disorders, EFV-based regimen, age, clinical stage and CNS disorders. Challenges: Require more intensive laboring, time consuming, costly, difficult to maintain in long terms and not feasible to apply at national wide

9 COLLECTING SAFETY DATA RELATED TO ARV Targeted spontaneous reporting (TSR) Spontaneous reporting (SR) Cohort event monitoring (CEM) Targeted spontaneous reporting (TSR) Pal S et al. Drug Saf. 2013, 36, 75-81

10 Objectives PILOTING TSR IN VIETNAM To assess the feasibility of TSR approach in monitoring ARV toxicity To monitor and document adverse events among those taking ART for prevention and treatment. To improve physicians capacity in monitoring and documenting adverse events related to ARV drug use Pilot of TSR to monitor adverse events of TDF and EFV DienBien và CanTho provinces (from 02/ /2013) Hanoi (from 05/ /2014) Feasible, affordable and sustainable at restricted-source countries

11 TSR implementation in Dien Bien and Can Tho Dien Bien Can Tho Treatment as Prevention (TasP study) among serodiscordant couples: HIV positive partners received ART regardless of CD4 count Study couples received standard care and prevention Monitor adverse events related to TDF and EFV Feasibility of TSR in a research environment. DienBien (6 OPCs), CanTho (5 OPCs)

12 TSR implementation in Hanoi (from 05/ /2014) Ha Noi To monitor toxicity of TDF and EFV among patients: - Newly treated with TDF/3TC/EFV - Switching from d4t-based regimen to TDF/3TC/EFV To assess feasibility of TSR approach in monitoring ARV toxicity in HIV program Implement in all 7 out patient clinics (OPC) in Hanoi

13 TSR implementation: setting-up Design a specific ADR reporting form

14 TSR implementation: setting-up Development of guideline on recording form

15 TSR implementation: setting-up Training for healthcare workers M&E, technical assistance at HIV/AIDS clinics

16 TSR implementation: data collection Detection of adverse events Asking patients on ADR that they may encounter in all follow-up visits (CNS symptoms related to EFV) Testing serum creatinine periodically (TDF induced renal toxicity) Filling in ADR reporting form Doctors identify adverse events (if any) fill in the toxicity reporting form Nurses/other healthcare workers fill in the remaining part of the form Contact person at OPCs collect all reports and periodically send to the National DI&ADR Center before the 5 th day of the next month

17 ADR reporting form Patient information to be filled by nurses ADR information to be filled by doctors

18 TSR implementation: data collection Reporting cycle Adverse events occurred in patients Reporting ART clinics Doctors, nurses Reporting Feedback National DI&ADR Center review, assessment Drug Information Feedback WHO - UMC Provincial HIV/AIDS Center (PAC) Making decision Viet Nam Administration of HIV/AIDS Control (VAAC)

19 Results: TasP study (DienBien and Can Tho) OPC Number of patients Number of AE reports OPC Tuan Giao district 21 0 OPC Muong Ang district 10 3 Dien Bien Can Tho OPC Muong Lay district 5 2 OPC Muong Cha district 6 2 OPC Dien Bien city 10 0 OPC Dien Bien Hospital OPC Thot Not district 8 0 OPC O Mon district 3 0 OPC Cai Rang district 7 0 OPC Ninh Kieu district 5 1 OPC Can Tho General Hospital 5 0 Total Patients experienced with AEs: 22.45% (all related to EFV) * Data till September 2013

20 Results: TasP study (DienBien and Can Tho) Characteristics of patients experienced with AEs Gender Age CD4 cells count (cells/mm 3 ) Female 14% Not documented 4% % % Male 86% % <350 41% >=350 55%

21 Results: TasP study (DienBien and Can Tho) CNS symptoms related to EFV AEs related to EFV No of reports % Dizziness Fatigue Insomnia Headache Nausea Vivid dream Hot flush Nightmares Anxiety Poor concentration Depression Others Reduce of sexual desire 1 4.5

22 Results: TasP study (DienBien and Can Tho) No of reports % Severity Grade Not documented Onset CNS symptoms related to EFV < 1 week % 1 week to 1 month % 1 month - 6 months % Not documented %

23 Results: TasP study (DienBien and Can Tho) CNS symptoms related to EFV AE management No of reports % Reduce dosage 0 Stop medicines 0 Switching regimen % Using other drugs to treat AE symptoms 0 Others (consultancy, change the time of taking drugs, taking with a lot of water ) % Not documented %

24 OPC Results: Pilot in Hanoi Number of patients Number of AE reports OPC Ba Đình district OPC Dong Da district NA NA OPC Hoang Mai district OPC Thanh Xuan district 7 7 OPC Tay Ho district 49 5 OPC Ba Vi district OPC Dong Anh district OPC Tu Liem district OPC Long Bien district 36 8 OPC Gia Lam district OPC Ung Hoa district OPC Son Tay Hospital Not reported Not reported OPC Soc Son district 12 4 OPC Hospital OPC Dong Da Hospital 47 8 OPC Ha ĐOng Hospital OPC Hà Nội Lung Hospital 50 8 Total Patients experienced with AEs: 39.8% (EFV: 217 cases, TDF: 14 cases)

25 Results: Pilot in Hanoi Characteristics of patient experienced with AEs Gender Age CD4 cells count (cells/mm 3 ) >=50 5.4% % Not documented 0.9% Female 28.8% % % >= % Male 71.2% % < %

26 Results: Pilot in Hanoi CNS symptoms related to EFV AEs related to EFV No of reports % Dizziness Fatigue Hot flush Headache Insomnia Vivid dream Nausea Anxiety Nightmares Poor concentration Aesthesia Others Paranoia Reduce of sexual desire Depression Suicide thought 2 0.9

27 No of reports % Severity Grade Grade Grade Not documented Onset Results: Pilot in Hanoi CNS symptoms related to EFV < 1 week week to 1 month month - 6 months Not documented

28 Results: Pilot in Hanoi Central nervous system AEs related to EFV CNS symptoms related to EFV AE management No of reports % Reduce dosage 0 Stop medicines 0 Switching regimen Using other drugs to treat AE symptoms Others (consultancy, change the time of taking drugs, taking with a lot of water ) Not documented

29 Patients code Gender Results: Pilot in Hanoi TDF induced renal toxicity Creatinin before using TDF Date Creatinin at time of reporting Date TDF start date 78 M 65 01/11/ /07/ /07/ F 70 07/11/ /07/ /07/ M 80 19/05/ /07/ /07/ M 74 01/11/ /07/ /07/ F 60 08/11/ /07/ /07/ M 89 08/11/ /07/ /06/ M 64 27/05/ /07/ /06/ M 76 25/05/ /07/ /06/ F 71 15/11/ /07/ /06/ M 87 15/11/ /07/ /06/ M 89 15/11/ /07/ /06/ M 90 09/05/ /07/ /07/ M 95 22/11/ /07/ /06/ M /11/ /07/ /06/ patients need to switch to other regimen

30 Challenges in AE monitoring and recording at OPC Due to huge workload at OPC: Healthcare workers have not paid much attention to AEs Lack of knowledge and skills among healthcare workers to detect and assess AEs Record and report AEs have not become a routine work Transient/mild adverse events has not been recorded by physicians or not reported by patients. Missing data with AEs occurred when patients at home, only persisted AEs at follow-up visit could be taken into account by healthcare workers Uncompleted and inaccurate information in AE reports

31 AE report collection Technical assistance and close monitoring of Hanoi PAC have an impact on number of AE reports ADR reports from TasP study is less frequent especially in Can Tho: recording other information of the study may compromise ADR information recording/reporting Reporting channel need to be revised OPC intended to send report to PAC (their supervision) than to ADR centre (as required) Weak adherence to timeline of sending reports by some OPCs Loss reports when sending by post office ADR reports sent by were likely more update and accurate

32 1. Feasibility: LESSON LEARNT Structured reporting form (clear and simple) Increase in number of reports (compared to spontaneous reporting) 2. Training on detecting, recoding and reporting skills is vital for success. 3. Providing TA and monitor from provincial level to OPC is crucial 4. Close communication, feedback between National DI & ADR Center, VAAC, PAC and OPCs.

33 RECOMMENDATIONS Toxicity monitoring of ARV using TSR approach is applicable and relevant for concentrated epidemic and limited resource as Vietnam. Training and guidelines are needed for implementation and scale up More advocacy on ARV toxicity monitoring is needed to improve awareness of ARV toxicity monitoring. Support and commitment from HIV program manager is important

34 Scaling up VAAC recommends to implement new reporting form (based on TSR form) in 5 high burden provinces

35 Scaling up VAAC required PACs to monitor and report AEs using the national ADR reporting form (August 2013) TSR promotes spontaneous reporting

36 Collaborations Provincial AIDS Centre

37 Thanks for your attention