AEFI SURVEILLANCE

KOMNAS PP-KIPI

Dr. Nastiti Kaswandani, SpA(K)

PERTEMUAN DESIMINASI PEDOMAN PENYELENGGARAAN FARMAKOVIGILANS OBAT
PROGRAM ATM (AIDS, TUBERKULOSIS, MALARIA)
ACACIA HOTEL, 3 NOVEMBER 2014
 Content

• Background

• Surveillance system

• Activities

• Causality assessment
 INDONESIA
Nakho n Si Tha m ma rat

Phuket
Kuda t Davao

Kota Kinab a lu
Kota Ba haru Sa nd aka n
Banda Aceh
Georg e Town Bandar Seri Begawan Melalap
Malaysia Natuna Besar Brunei
Ace h
Celebes Sea
Medan Kuala Lumpur Malaysia Bintulu
Sulawesi Utara
Simeulue Riau Sibu Borneo
Pa lo h Kuchin g
Sumater a UtaraDum ai Manado
Nias Riau
Singapore Kalimantan Timur
Te rnate Halmahera
Kola m ob ag u
Pekanbaru Sintang Kalimantan
0° Pontianak Sulawesi Tengah
Kalimantan Barat Samarinda Luwuk
Padang Reng at
Te lukb ata ng Kalimantan Tengah Palu Kepula uan Sula So rong
Jambi Belinyu

Mo luc
Sumater a Bar atJambi Sa rmi
Siberut Bangka
Sumatra Palangkaraya Kolo nod ale Jayapura
Belit ung Sulawesi

cas
Palembang Kand awa ng an Ma lili
Lubukling ga u Ceram Irian Jaya
Kalimantan Selatan
Sumater a Selatan To bo ali
Banjarmasin Ma jene Kendari
Bengkulu Buru Ambon New Guinea
Kola ka
Sulawesi Selatan
Bengkulu Greater Sunda Islands
Tanjungkarang- Telukbetung Sulawesi Tenggara Maluk u Irian Jaya
Java Sea Ujungpandang
Jawa Bar at Jawa Tengah Banda Sea
Lamp ung
Kepula uan Aru
Selat Sunda Jakarta Semarang Madura
Indian Ocean Bandung Java Surabaya
Sumbawa Kepula uan Tanimbar
Jawa Tim ur Bali Rab a Lara ntuka
Yogyakarta Mataram Lab uha nba jo
Banyuwang i Mera uke
Yagyakarta Denpasar Lab y Ba lat Flores Dili
Timor Timur Arafura Sea
LombokNusa Tenggara Barat Wainga pu Timor
10° Sumba Nusa Tenggara Timur
Christmas Isla nd (Austl.) Kupang
Timor Sea
Lesser Sunda Isla nds

1.919.440 km2 , 17.508 islands Australia

100° 110° 120° 130° 140°

33 Provinces ; 497 Districts ; 9440 PHC ; 2263 Hospitals

± 4,8 million newborn annually
 Vaccine Safety in Immunization
Programmes

• POTENTIAL STAGES IN THE EVOLUTION OF AN IMMUNISATION PROGRAMME.

• DIAGRAM ADAPTED FROM CHEN RT ET AL. THE VACCINE ADVERSE EVENT REPORTING SYSTEM
VACCINE, 1994: 12(6):542–550.
 New Vaccine Intorduction
• New vaccine :
1. Td : 2011 replacing TT in grade 2 and 3 in primary school
2. Hib : 22nd aug 2013 in 4/33 provinces
2014 all provinces

• 2013: introduce new booster schedule  dpt-hb-hib and measles

• Bio farma
National Immunization Scedule

Conduct Screening before TT Immunization for CBAW

Immunization Coverage By Antigen (%)
Supplement Immunization Activity
East Java 2012 - 2013
AEFI Surveillance System
 History
• 1997: Director General CDC
Working Group On AEFI

• 1998: Reorganization
Job Description:
- Surveilance AEFI
- Communication With Expert
- Analysis Causalities & Follow Up
- Coordination With Provincial & District Level
- Report Activities To MOH By DG DC & EH

Ministry Of Health
National Committee Of Aefi (Update Every 3 Years)

Recent Decree: 10th December 2012 Minister Of Health Ri

No.431/Menkes/Sk/Xii/2012
 NC-AEFI, 2012 - 2016
Position Occupation Work Place
Chairman Pediatrician National Public Hospital (RSCM),Indonesian Pediatric Society (IDAI)
Vice Chairman Pediatrician Maternal and Child Hospital,Indonesian Pediatric Society(IDAI)
Secretary Epidemiologist NC-AEFI,Indonesian Medical Association (IDI)
Member Pediatrician National Public Hospital (RSCM),Indonesian Pediatric Society (IDAI)
Member Medicolegal MoH,Indonesia's Health Law Association (PERHUKI)
Member Pediatrician National Public Hospital (RSCM),Indonesian Pediatric Society (IDAI)
Member Pediatrician National Public Hospital (RSCM),Indonesian Pediatric Society (IDAI)
Member Pediatrician National Public Hospital (RSCM),Indonesian Pediatric Society (IDAI)
Member Pediatrician National Public Hospital (RSCM),Indonesian Pediatric Society (IDAI)
Member Forensic Departemen of Forensic, Medical Fac. Univ. of Indonesia
Member Internist Indonesian Society of Internal Medicine
Member OBGYN Indonesian Society of Obstetrics and Gynecology
Member Medicolegal Law Bureau, MoH
Member Pharmacist DG of Pharmacy and Public Drug, MoH
Member Pharmacist NRA
Member Pharmacist NRA
Secretariat Admninistration EPI
Secretariat Admninistration EPI
Secretariat Admninistration EPI
Secretariat Admninistration EPI
 Type Of Meeting

• Regular meeting:
2 times per year
Core team
• Causality assesment
• Special meeting:
Issues from :
• Field
• Media

• Others: special request from government

Causality Assessment Meeting in 2012
 Other AEFI Activities in 2012 (Training,
Investigation, Assistance to Province, National
Meeting)
Causality Assessment Meeting in 2013
 Other AEFI Activities in 2013 (Training,
Investigation, Assistance to Province, National
Meeting)
 AEFI Activities

Training and
Causality Workshop
NC – AEFI
Assessment Causality
Meeting
TOT Assessment

Data Study tour in

Management Bangkok
Training
 AEFI Activities
WHO E-Learning Module Meeting

Module Editing Module Editing

Review Meeting for

E learning module
Provincial Committee (PC-AEFI)
 Provincial Committee (PC-AEFI)

• All provinces established PC – AEFI (33 provinces)

• Job description:
To coordinate with HC, local government, referral hospital
To make field classification of AEFI case
To provide information to the public and the media
concerning AEFI reports
To coordinate with the NC-AEFI
To report to the NC-AEFI for the classification of AEFI
To help solving the AEFI case in the field
 Focal Person AEFI Surveillance
Provincial Level

Central level  two EPI staffs Provincial level  two staffs

assigned to be the focal person Each focal person from National
assigned to be the focal person
in National AEFI Surveillance and Provincial level has Decree
in each provinces
 AEFI Report Mechanism
Ministry of Health

National Committee AEFI Directorate General DC – E H NRA

Cq. Immunization sub directorate
Vaccine
Manufacture
Local Committee AEFI Provincial Health Local NRA
Office

District Health Hospital

Office

Community Health Centre

Giving Repport

Investigation
Community
Coordination
 AEFI Form
Non Serious AEFI Serious AEFI
AEFI Investigation Form
 AEFI National Guideline

Moh Regulation No. 42/2013 Technical Guidance on AEFI

Surveillance 2011
AEFI Reporting & Investigation
2012 - 2103)
Criteria 2012 2013

Total number of AEFI cases No =10.469 No =18.621

reported Rate =0,0010 Rate =0,0017

Number of serious cases reported BCG=22 BCG

with each antigen (add DTP/ HB=80 DTP/ Penta
appropriately) OPV = 2 OPV
Measles = 19 Measles

Number of AEFI cases investigated 163 156

Number of AEFI cases which were 163 156

reviewed and analyzed by AEFI
committee
 Constraints
• Rumors easily to spread
• Health officer still does not
know that all AEFI should be
reported although already
been trained
• High staff turn over
• Quality of recording and
reporting
• Completeness and timeliness
Oppurtunities
• There Is Already Good
Coordination Between EPI,
NRA, Referral Hospital,
Health Insurance
• Focal Person Of AEFI
Surveillance In Every
Provinces Already Appointed
• Opportunity To Conduct
Training To Strengthen AEFI
Surveillance Performance
 Program Priorities in 2014
• Conduct 2nd batch of focal person training of AEFI
surveillance to improve coordination of AEFI reporting
system

• Clarify the funding mechanism of aefi case in the new

national health insurance system (universal health coverage)

• Build a good communication system to all pc aefi

• Establish focal person in every district and health center in

all provinces
 Causality And Causality Assessment

Causality* Causality
• Is the relationship between Assessment
two events (the cause and • Determining if such a
the effect), where the second relationship exists and if so to
event is a consequence of the what extent
first

*A direct cause is a factor in absence of which the effect would not occur (necessary cause).
*Sometimes, there are multiple factors that can precipitate or function as co-factors for the effect (event) to
occur.
 Why Causality Assessment For AEFI?
To Avoid Automatically Concluding That

“The Event Happened After Vaccination, Therefore It Happened Because Of

Vaccination”…

Unvaccinated group
Best evidence is randomized trial
comparing AEFI in vaccinated and
non vaccinated groups.
Vaccinated group

But…never large enough to detect rare events.

 CIOMS/ WHO Cause Specific Definition Of Aefis

1 2 3 4 5
Vaccine Vaccine quality Immunization Immunization
product-related defect-related error-related anxiety-related Coincidental
reaction reaction reaction reaction event

EXAMPLE
Failure by the EXAMPLE
manufacturer EXAMPLE A fever after
EXAMPLE to completely EXAMPLE vaccination
Thrombocyto Vasovagal (temporal
inactivate a Transmission
penia after syncope in an association)
lot of of infection by
Measles adolescent and malarial
inactivated contaminated
vaccine following parasite
polio vaccine multidose vial.
vaccination. isolated from
leads to cases
of paralytic blood.
polio.
Case Selection For Formal Causality
Assessment Death, Hospitalization, Significant
disability, Life threatening, or Congenital
Serious anomaly/ Birth defect
AEFI

Clusters &
events
above
expected
rate/
severity

Evaluation
of
suspected
Signals

As decided by reviewing team / committee

If immunization error is suspected
Significant events of unexplained cause
Other within 30 days of vaccination
AEFI* Events causing significant parental or
community concern (e.g. Hypotonic
Hyporesponsive Episode (HHE), febrile
seizures)
Prerequisities for assessing causality for
an AEFI case

• The AEFI case investigation should have been completed

• All details of the case should be available at the time of
assessment
• There must be a “valid diagnosis”
• The valid diagnosis refers to the extent to which the
unfavorable or unintended sign, abnormal laboratory
finding, symptom or disease is defined.
 Causality Assessment Steps

Classification
Algorithm
Checklist
Eligibility
 Why 4 Steps?
Step 3: Step 4:
Step 1: Eligibility Step 2: Checklist Algorithm Classification

To determine To To obtain a To categorize

that the AEFI systematically trend on the
case satisfies review causality with association of
minimum available the checklist the AEFI to
criteria for information information vaccine /
causality vaccination
assessment
Step 1: Eligibility
• Ensure AEFI investigation is completed and all details of the case is
available
AEFI case • Retain case details in a retrievable database

• Identify one vaccine (implicated) administered before this event

Identify
vaccine(s)

• Select the unfavorable or unintended sign, abnormal laboratory finding,

symptom or disease you want to check causality.
Valid
Diagnosis

• Brighton Collaboration definition, Standard literature definition,

National definition or other approved definition
Case
definition
Step 2: Checklist
Y N UK NA
I. Is there strong evidence for other causes?

II. Is there a known causal association with the Vaccine /
Vaccination

• Relationship with vaccine ingredients
• Immunization error
• Relationship with vaccine administration

II (Time). Was the event within the time window of increased

risk?

III. Is there a strong evidence against a causal association?

IV. Other Qualifying Factors

 Step 3: Algorithm (summary)

I A. Inconsistent III A. Inconsistent

causal causal association
association to to immunization
immunization

Yes Yes
II. Is there a
III. Is there a
I. Is there strong known causal IV. Review other
strong evidence
evidence for association with qualifying factors
against a causal
other causes? the vaccine/
association?
vaccination

Yes

Is the event No
II (Time). Was the classifiable? IV D.
event within the Unclassifiable
time window of
increased risk? Yes
Yes

II A. Consistent IV A. Consistent IV C. Inconsistent

causal causal IV B. causal association
association to association to to immunization
Indeterminate
immunization immunization
 Step 4: Classification
A. Consistent causal B. Indeterminate C. Inconsistent causal
association to immunization association to immunization

A1. Vaccine product-related B1. *Temporal relationship is

reaction (As per published consistent but there is
literature) insufficient definitive
Adequate evidence for vaccine causing
event (may be new vaccine- C. Coincidental
informatio A2. Vaccine quality defect- linked event) Underlying or emerging
related reaction condition(s), or condition(s)
n available caused by exposure to
B2. Qualifying factors result in something other than vaccine
A3. Immunization error-related conflicting trends of
reaction
consistency and inconsistency
with causal association to
immunization
A4. Immunization anxiety-
related reaction

Unclassifiable
Adequate
information
Specify the additional information required for classification
not available

*B1 : Potential signal and maybe considered for investigation

 Key Considerations

The "critical" part is the valid diagnosis.

The first conclusion may not be final: as more

information becomes available, the causality
can change
 Multiple Vaccines, Multiple AEFI And Clusters
Multiple Vaccines in the same patient Multiple AEFI in the same
patient
Each event should be listed
separately and specific
Each vaccine should be eligibility question (step 1)
assessed separately asked and independently
evaluated.

AEFI cluster

Each patient in the

cluster should be
separately
evaluated
 Who Should Assess AEFI Causality
• A reviewing team/ committee that should
• Be independent
• Free of real or perceived government, industry conflicts
of interest
• Have broad range of expertise
• Infectious diseases, epidemiology, microbiology,
pathology, immunology, neurology, vaccine program
expertise, other…
• Have written terms of reference (tor)
• Can make use of an existing drug
causality assessment team but
modify and adapt to fit vaccines.
 What Can Go Wrong?
Causality assessment not done, not systematic, not done by trained
personnel and/or not done timely

Information in AEFI report is so limited that causality assessment

cannot be done

Lack of expertise and/or independence of the review committee

responsible for formal causality assessment undermines credibility

Non analysis of AEFI data may delay recognition of clusters and

programme errors

Lack of communication of findings, not addressing all target audiences, or

lack of diplomacy and/or cultural sensitivity
 Revised Causality Assessment Scheme
Ensures that AEFI
cases are classified Flexible approach that
Incorporates major
according to the evolves as more
criteria affecting
CIOMS/ WHO information becomes
causality*
guidelines available**

Simple – no
Can be adapted to
technology involved;
Minimizes errors computer logic if
can be used in
necessary
heterogenous settings

A convenient tool to
teach and learn

*Restricted ability to associate novel, previously unknown AEFI

**limitation due to insufficient information available for individual cases
 Conclusion

AEFI
Feedback
Detection

Causality
Notification
assessment

Analysis Investigation
TRIMAKASIH