Pharmacovigilance in Thailand Ms. Wimon Suwankesawong Head of - - PowerPoint PPT Presentation

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Pharmacovigilance in Thailand Ms. Wimon Suwankesawong Head of - - PowerPoint PPT Presentation

Apr 09, 2023 472 likes •956 views

Pharmacovigilance in Thailand Ms. Wimon Suwankesawong Head of Health Product Vigilance Center Food and Drug Administration Thailand 1 Outline Overview of Thai PV system Thai Vigibase PV & PGx Research 2 National level PV network and

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Pharmacovigilance in Thailand

  • Ms. Wimon Suwankesawong

Head of Health Product Vigilance Center Food and Drug Administration Thailand

1

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Outline

Overview of Thai PV system Thai Vigibase PV & PGx Research

2

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Overview of Thai PV system

PV network and management National level Hospital level

Surveillance methods utilized in PV Passive method Active method

3

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Thailand

  • PV system and National

Center were set up in 1983.

  • Thailand joined WHOPIDM

as 26th member in 1984

  • Population : 64.8 million (2014)
  • Provinces : 77

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Thai PV network and management t : National level

Sources of reports

Voluntary Research partnerships

Safety y Signal WG & Safety y gnal WG & Sig PV Advisory subcommittee

Drug committee

Signal detection

Thai ai Vigibase

Regulatory Regulatory Action

Academia

Volunt

Regulatory requirement

Safety Monitoring Program

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Flow of reports and feedback loop in Thailand

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MAH

Sources of reports

www.fda.moph.go.th/vigilance

Acknowledgement

AE online reporting system

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Safety Monitoring Program

  • Status of conditional approval new drug

specially controlled drug = prescription drug

  • Distribution
  • nly to medical institutes and hospitals
  • Drug safety monitoring

ADR reports (ICSRs)

  • Report: every 4 months

volume of production, re-packing or importation sale volume

Summary of drug safety monitoring

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Pharmacovigilance at Hospital Level

Patients

Physicians Pharmacists

1 PV contact person

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ADR Diagnosis

Notify Rx

Data collecting, Causality assessment & feed back to reporter

ADR Treatment

Minimize Risk

  • Counselling
  • Provide alert cards

Submit reports to NHPVC

Follow up

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Drug Alert Cards

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Suspected drug name

ADR

Causality assessment Reporter

SCARs cards

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Dispensing program

Patient bed

Medical records

Risk minimization measures .

Warning message

Patient chart

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Causality assessment method

WHO-UMC method Naranjo’s algorithm Thai algorithm

(modified WHO-UMC method)

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Surveillance methods utilized in PV

ICSRs Passive

Spontaneous reporting Targeted spontaneous reporting

Active

Intensive Monitoring Cohort Event Monitoring (CEM)

Registries

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Passive Surveillance Methods

  • Spontaneous reporting

Main method for all health product

  • Medicine including traditional medicine
  • Biological product including vaccine
  • Targeted spontaneous reporting

Conditional approval new drug :

  • Safety Monitoring Program(SMP)

Herbal medicine in NEDL Medicine use in public health program

  • Anti-TB dug, ARV

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Active Surveillance Methods

  • Intensive (hospital) monitoring

Product of interest

  • New drug , High alert drug
  • Cohort event monitoring (CEM) : start 2015/16

Anti -TB drug

  • new drug , new regimen
  • Registry

Thai EPO registry

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Thai Vigibase Characteristics of database SCARs reports SJS/TEN Signal generation WHO-UMC Thai FDA Researche & Publications

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Number of reports by year in Thai Vigibase

(1984-2014.)

10000 20000 30000 40000 50000 60000 70000 MAH HCPs

  • About 600,000 reports were accumulated
  • Over half of them have been received in last six year,

about 50,000 each year.

  • Only 2.1% of reports were submitted by MAH.
  • ~ 20 % serious cases were received each year.

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Number of SCARs Reports

(1984-2014)

SCARs

  • No. (%) [n = 18,896 reports

19,080 reactions]

Stevens Johnson Syndrome (SJS)

12,162 (63.7)

Erythema Multiforme (EM)

4,817 (25.2)

Toxic Epidermal Necrolysis (TEN)

1,282 (6.7)

DRESS Syndrome

504 (2.6)

Epidermal Necrolysis

315 (1.7)

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Number of SJS/TEN reports by year in Thai Vigibase (1984-2014)

200 400 600 800 1000 1200 1400

1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 3 6 4 7 17 11 11 18 20 42 56 68 65 122104 152 262263 328 475 538 638631 707 892 1253 1092 1046 943 905 723

1 1 1 1 2 1 2 3 3 9 8 8 8 17 15 21 20 22 33 18 2 11 14 10

  • Total SJS/TEN reports = 11,402
  • Proportion of SJS/TEN reports in Thai Vigibase = 1.8

(range 1.3-2.6)

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Characteristics of SJS/TEN Reports

(1984-2014) Characteristics

  • No. (%) [n = 11,402 reports

11,457 reactions]

Sex

  • Female/Male

5,898 (51.7)/5,470 (48.0) Age

  • < 15

817 (7.2)

  • 15-30

1,762 (15.5)

  • 31-45

3,140 (27.5)

  • 46-60

2,136 (18.7)

  • > 60

2,615 (22.9) Causality assessment

  • Certain

711 (6.2)

  • Probable

7,636 (67.0)

  • Possible

2,918 (25.6)

  • Unlikely

22 (0.2)

  • Unclassified/ unassessable

115 (1.0) Death outcome 231 (2.0 )

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Most suspected drug & SJS/TEN

(1984-2014)

500 1000 1500 2000 2500 2186 1488 10921018 985 526 310 288 218 202 196 186 184 175 169 144 143 126 120 120

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SJS-TEN Cases/ 1,000,000 Mid year population Thailand (2002-2013)

5.2 7.5 8.6 10.3 10.1 11.2 14.1 19.7 17.1 16.3 14.7 14.0 0.0 5.0 10.0 15.0 20.0 25.0

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

  • Average 12.4

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Total ADR Cases/ 1,000,000 Mid year population Thailand (2002-2013)

291.5 331.3 409.6 484.1 490.5 553.1 682.1 973.3 1004.7 984.0 878.8 902.3 0.0 200.0 400.0 600.0 800.0 1000.0 1200.0

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

  • Average

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Signal Generation : WHO

  • Rifater (Isoniazid+ Rifampicin + Pyrazinamide) :

dyspnoea (1/3)

WHO SIGNAL April 1997

  • Arthemether : severe headache (9/10)

WHO SIGNAL April 2001

  • Colchicine : Stevens-Johnson syndrome (8/23)

WHO SIGNAL September 2002

  • Nitrates : EM, SJS and/or Epidermal necrolysis (1/61)

WHO SIGNAL June 2002

  • Propylthiouracil : SJS (5/12) , EM (5/15) and Epidermal

necrolysis (4/5)

WHO Newletter No2 2013

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Signal Generation : Thai FDA

  • Cassia siamea (leaf) ใบขีเหล็ก : hepatic injury (2000)
  • Voluntary withdrawal
  • Increase frequency of PRCA associated with EPO (2004-2005)
  • Thai EPO Registry
  • Hypersensitivity reactions : Andrographis paniculata (ฟ้าทะลาย

โจร) containing drugs (2012-3)

  • HPVC Safety News
  • Streptomycin : Steven-Johnson syndrome (2013)
  • Aminoglycoside - legal warning
  • Eperisone : Anaphylactic reaction (2013)
  • HPVC safety News

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Reported cutaneous hypersensitivity reactions associated with thioacetazone, Thailand, 1984–1993

  • These reports are consistent with

the publications from Africa.

An increased risk of severe

cutaneous reactions associated with the use of thioacetazone in persons with HIV infection.

  • It is notable that the timing of the

reporting peak coincides with the evolution of the HIV epidemic in Thailand

  • Ref. Pharmacovigilance and tuberculosis: applying the lessons of thioacetazone

WHO Bulletin 2014;92:918-919.

Bullous eruption (n = 1); Exfoliative dermatitis (n = 4); SJS (n = 19);TEN (n = 1). EM (n = 2);

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Researches & Publications

using Thai Vigibase

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Evaluation on reporting serious adverse drug reactions in Thai SRS: a case study of SJS and TEN

Thesis by Wittaya Prachachalerm

  • Research design

Cross-sectional design

  • Research setting:

14 selected hospitals from five regions of Thailand

  • Compared cases in 2005

Thai Vigibase 14 selected hospitals

  • Retrieved by using ICD-10 computerized system
  • Verified with patient medical records

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101 cases

14 Hospitals Medical Records

182 cases

28

81 Cases 9 cases

Thai Vigibase 110 cases

Discordant submission% = 9/110* 100= 8.18 Under reporting% = 81/182* 100= 44.51

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SLIDE 29
  • Detection of Adverse Drug Reaction Signals in the Thai

FDA Database : Comparison Between Reporting Odds Ratio and Baysian Conference Propagation Neural Networks Methods.

Drug Information Journal: 2010;44(4):393-403.

  • Safety of Herbal Products in Thailand An Analysis of

Reports in the Thai Health Product Vigilance Center Database from 2000 to 2008”

Drug Safety: 2011; 34 (4): 339-350.

  • Characterization of Statin-Associated Myopathy Case

Reports in Thailand Using the Health Product Vigilance Center Database”

Drug Safety: 2013; 36 (2): 583-.591

Publications-1

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  • Signal detection for Thai traditional medicine:

Examination of national pharmacovigilance data using reporting odds ratio and reported population attributable risk.

Regulatory Toxicology and Pharmacology, Volume 70, Issue 1,

October 2014, Pages 407-412, ISSN 0273-2300

  • Characterization of Hypersensitivity Reactions Reported

among Andrographispaniculata Users in Thailand Using Health Product Vigilance Center (HPVC) Database.

BMC Complementary and Alternative Medicine:2014,14:515

  • Renin Angiotensin System Blockers associated Angioedema among

Thai Population: Analysis from Thai National Pharmacovigilance Database.

Accepted by Asia Pacific Journal of Allergy and Immunology (AJPAI)

Publications-2

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PV & PGx Research

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DMSC, Thai FDA, Hospitals in MOPH

DMSc (10 buildings, 12 regional centers Permanent secretary

  • ffice,

800 hospitals centers Thai FDA, Health Product Vigilance Center HITAP, Health economic evaluation unit

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26th August 2009 (BrainSTROMING)

(www.thailandpg.org, www.facebook.com/ThailandPGx)

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Ref: Association between HLA-B*1502 and Carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia2010, 51(5): 926-930

10 20 30 40 50 60 70

c

  • n

t r

  • l

l > > >

Frequencies of certain HLA-B alleles in CBZ-induced SJS/TEN versus CBZ tolerant patients (Tassaneeyakul W., 2010)

table(HLA. merge$CHA LLENGE)

*

P-value: 2.89 x 10-12 OR: 54.76

88.7 % sensitivity 88.7 % specificity Based risk (2.9/1000) PPV 1.92% (1/50) NPV 99.96% (2/1000)

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~90% of CBZ-SJS/TEN is preventable by preventative test of HLA-B*15:02

47 51 74 61 70 80 99 161 108 106 5 5 7 6 7 8 10 16 11 11 50 100 150 200 250 50% overdiagnosis CBZ-SJS/TENS cases in Thai FDA Pharmacovigilance database 40% underreported After HLA-B*1502 testing

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Brainstorm

Proposed for universal screening : HLA-

B* 15:02

Economic evaluation of HLA-B* 15:02 screening or CBZ-induced SCAR in Thailand

PGx Testing Centers

Thailand PharmacoGenomics Network (TPGN)

PV & PGx PGx Studies

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Economic evaluation of HLA-B* 15:02 screening or CBZ-induced SCAR in Thailand

AT QALY 120,000 Baht (4000 USD)

Testing for Neuropathic pain is cost effective Testing for Epilepsy is borderline cost effective

  • Dr. Waranya Rattanavipapong

(HITAP)

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Location of regional medical science centers providing PGx testing in MOPH (9 centres)

Nonthaburi Khonkaen Udonthani Phitsanulok Nakornsawan Samutsonkarm Trang Songkla Chiangrai

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DNA

3 days guaranteed turn around time

DNA extraction

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Nation-WIDE PGx SERVICE Announcement

07/06/2012

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Pilot free testing for all CBZ prescribed in Bangkok

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18 Hospitals participated in ThaiSCAR-PGx Phase I study

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Line listing menu Search term: SJS How to detect cases for the research ?

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Number of DNA samples collected based on suspected drug (2012-2014)

5 10 15 20 25 30 35

Cotrimoxazole Phenytoin Allopurinol Phenobarbital Tetracyclin Dapsone Ibuprofen Nevirapine

CH CR ID LP MG MW PB PS RY SK SN SO SR ST TB TS

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Number of SJS/TEN reports by year in Thai Vigibase (1984-2014)

200 400 600 800 1000 1200 1400

1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 3 6 4 7 17 11 11 18 20 42 56 68 65 122104 152 262263 328 475 538 638631 707 892 1253 1092 1046 943 905 723

1 1 1 1 2 1 2 3 3 9 8 8 8 17 15 21 20 22 33 18 2 11 14 10

  • Total SJS/TEN reports = 11,402
  • Proportion of SJS/TEN reports in Thai Vigibase = 1.8

(range 1.3-2.6)

Nation wide testing service

45

Brainstorming

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Signal generation Discovery & Validation

Utility

Implementation

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Acknowledgement

  • Dr. Surakameth Mahasirimongkol