TARGETED SPONTANEOUS REPORTING FOR ADVERSE EVENTS …€¦ · TARGETED SPONTANEOUS REPORTING FOR...

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, 7-8th November 2013

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)

NATIONAL GUIDELINE FOR HIV/AIDS DIAGNOSIS & TREATMENT

Switch from AZT/d4T + 3TC + NVP to TDF +

3TC + EFV/NVP

PHARMACOVIGILANCE PRACTICE IN VIETNAM

1994: Foundation of the 1st ADR center 1999: became

full member of WHO-UMC

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

2009: Foundation of The National DI & ADR Center

PV SYSTEM PHP’s SYSTEM effective linkages

National level

Regional level

Healthcare facilities

Patients

National level

Regional level

Province & district level

Patients

GOAL Develop a national PV system that effectively links with and supports

PHP’s practice ensuring drug safety

Strengthening the national PV system to support PHPs

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

COLLECTING SAFETY DATA RELATED TO ARV

Spontaneous reporting (SR)

2010 2011 2012

No of ARV reports 16 11 15

Total reports received 1807 2407 3024

% 0,88 0,46 0,49

Number of spontaneous reports related to ARV received by the National PV Center

Launched in 1994 and mandated by law since 2005 for healthcare professionals

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

Spontaneous reporting (SR)

Targeted spontaneous reporting (TSR)

Cohort event monitoring

(CEM)

Targeted spontaneous reporting (TSR)


Pal S et al. Drug Saf. 2013, 36, 75-81

PILOTING TSR IN VIETNAM

Objectives 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 - 12/2013) Hanoi (from 05/2013 – 05/2014)

Feasible, affordable and sustainable at restricted-source countries

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)

Ha Noi

TSR implementation in Hanoi (from 05/2013-05/2014)

TSR implementation in Hanoi

• 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

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

TSR implementation: setting-up

Development of guideline on

recording form

Training for healthcare workers

TSR implementation: setting-up

M&E, technical assistance at HIV/AIDS clinics

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 5th day of the next month

TSR implementation: data collection

Patient information to be filled by nurses

ADR information to be filled by doctors

ADR reporting form

Reporting cycle

Adverse events occurred in

patients

ART clinics Doctors, nurses …

National DI&ADR Center review, assessment Drug Information

Provincial HIV/AIDS Center (PAC)

Viet Nam Administration of HIV/AIDS Control (VAAC)

WHO - UMC

Reporting Re

port

ing

Feedback

Feedback

Making decision

TSR implementation: data collection

OPC Number of patients

Number of AE reports

Dien Bien

OPC Tuan Giao district 21 0

OPC Muong Ang district 10 3

OPC Muong Lay district 5 2 OPC Muong Cha district 6 2 OPC Dien Bien city 10 0 OPC Dien Bien Hospital 18 14

Can Tho

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 98 22

* Data till September 2013

Patients experienced with AEs: 22.45% (all related to EFV)

Results: TasP study (DienBien and Can Tho)

Age

Male 86%

Female 14%

Gender

20-29 14%

30-39 68%

40-49 18%

Characteristics of patients experienced with AEs


CD4 cells count (cells/mm3)

>=350 55%

<350 41%

Not documented

4%

AEs related to EFV No of reports % Dizziness 16 72.7 Fatigue 16 72.7 Insomnia 12 54.5 Headache 10 45.5 Nausea 8 36.4 Vivid dream 8 36.4 Hot flush 6 27.3 Nightmares 5 22.7 Anxiety 4 18.2 Poor concentration 2 9.1 Depression 2 9.1 Others 2 9.1 Reduce of sexual desire 1 4.5

CNS symptoms related to EFV


No of reports % Severity Grade 1 10 45.5 Not documented 12 54.5

Onset < 1 week 18 81.8%

1 week to 1 month 1 4.55%

1 month - 6 months 1 4.55%

Not documented 2 9.09%



AE management No of reports % Reduce dosage 0 Stop medicines 0 Switching regimen 1 4.55% Using other drugs to treat AE symptoms 0 Others (consultancy, change the time of taking drugs, taking with a lot of water…) 3 13.64% Not documented 18 81.82%



OPC Number of patients Number of AE reports OPC Ba Đình district 62 22 OPC Dong Da district NA NA OPC Hoang Mai district 24 12 OPC Thanh Xuan district 7 7 OPC Tay Ho district 49 5 OPC Ba Vi district 27 13 OPC Dong Anh district 90 20 OPC Tu Liem district 47 37 OPC Long Bien district 36 8 OPC Gia Lam district 19 19 OPC Ung Hoa district 20 20 OPC Son Tay Hospital Not reported Not reported OPC Soc Son district 12 4 OPC Hospital 09 34 19 OPC Dong Da Hospital 47 8 OPC Ha ĐOng Hospital 34 20 OPC Hà Nội Lung Hospital 50 8 Total 558 222

Results: Pilot in Hanoi

Patients experienced with AEs: 39.8% (EFV: 217 cases, TDF: 14 cases)

Characteristics of patient experienced with AEs


Age Gender CD4 cells count

(cells/mm3)

15-19 0.5%

20-29 18.5%

30-39 58.1%

40-49 17.6%

>=50 5.4%

>=350 28.4%

<350 70.7%

Not documented

0.9%

Male 71.2%

Female 28.8%

AEs related to EFV No of reports % Dizziness 129 59.4 Fatigue 126 58.1 Hot flush 88 40.6 Headache 82 37.8 Insomnia 62 28.6 Vivid dream 61 28.1 Nausea 59 27.2 Anxiety 31 14.3 Nightmares 24 11.1 Poor concentration 21 9.7 Aesthesia 16 7.4 Others 16 7.4 Paranoia 6 2.8 Reduce of sexual desire 4 1.8 Depression 3 1.4 Suicide thought 2 0.9



No of reports % Severity Grade 1 151 69.59 Grade 2 47 21.66 Grade 3 5 2.3 Not documented 13 5.99

Onset < 1 week 133 61.29

1 week to 1 month 46 21.20

1 month - 6 months 13 5.99

Not documented 25 11.52



AE management No of reports % Reduce dosage 0 Stop medicines 0 Switching regimen 10 4.61 Using other drugs to treat AE symptoms 8 3.69 Others (consultancy, change the time of taking drugs, taking with a lot of water…) 148 68.20

Not documented 50 23.04

Central nervous system AEs related to EFV



Patients code Gender

Creatinin before using

TDF Date Creatinin at time

of reporting Date TDF start date

78 M 65 01/11/2012 160 11/07/2013 05/07/2013 209 F 70 07/11/2011 105 11/07/2013 05/07/2013 76 M 80 19/05/2011 124 11/07/2013 05/07/2013 6 M 74 01/11/2012 161 11/07/2013 05/07/2013

117 F 60 08/11/2012 115 11/07/2013 10/07/2013 55 M 89 08/11/2012 136 18/07/2013 10/06/2013

243 M 64 27/05/2013 125 11/07/2013 18/06/2013 73 M 76 25/05/2013 144 18/07/2013 20/06/2013

226 F 71 15/11/2012 135 18/07/2013 14/06/2013 206 M 87 15/11/2012 166 18/07/2013 14/06/2013 152 M 89 15/11/2012 147 18/07/2013 14/06/2013 112 M 90 09/05/2011 200 18/07/2013 10/07/2013 104 M 95 22/11/2012 123 11/07/2013 21/06/2013 139 M 126 29/11/2012 203 18/07/2013 21/06/2013

TDF induced renal toxicity

2 patients need to switch to other regimen


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

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 email were likely more update and

accurate

LESSON LEARNT

1. Feasibility: 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.

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

Scaling up VAAC recommends to implement new reporting form

(based on TSR form) in 5 high burden provinces

Scaling up

VAAC required PACs to monitor and report AEs using the national ADR reporting form (August 2013)

TSR promotes spontaneous reporting

Collaborations

Provincial AIDS Centre

Thanks for your attention

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