www.ncirs.usyd.edu.au

Vaccine Safety – In Australia and Internationally

NCIRS 20th Anniversary celebrations

November 2017

Associate Professor Kristine Macartney

Deputy Director, NCIRS

Vaccines held to highest possible safety standards

Why are so well placed to understand vaccine safety?

Clinical trials › Policy advisory › Evaluation › Clinical services

What we see determines our view

Case study

Population = 200,000

Vaccination coverage = 80%

Background event rate = 1 case per 10,000 (eg MS, GBS)

We need the whole picture !!!

Adverse Event

Total Rate = same (0.0001%)

Yes No

Vaccinated 16 159,984 160000

Not vaccinated 4 39,996 40000

Slide adapted from Alex Vorsters, Belgium with thanks

http://www.euro.who.int/__data/assets/pdf_file/0010/339625/Vaccine-safety-messages.pdf

Expected coincidental deaths following DTP vaccination in selected

countries

1999 USA

NCIRS analysis: Adverse events following immunisation, TGA ADRS database, 2000 to 2016, by

quarter of vaccination, by date of vaccination

2001: NCIRS commences analysis of national AEFI reports

NCIRS analysis: Adverse events following immunisation for children aged <1 year, ADRS

database, 2000 to 2016, by quarter of vaccination, by date of vaccination

Numbers of reports increase:

• New vaccines added

• Population growth

2005 NCIRS National vaccine safety workshop

Recruit patients that meet criteria

•Waiver of consent •Patient data collection •Collection of specimens

Analyses

Before – after incidence (RI)

VE using TND (controls)

Severity, risk factors

2007: 3 conditions

↓

2017: 9 conditions

Active Surveillance by NURSE

Emergency department

Inpatients

Intensive care

Laboratory results

Clinician notification

Sentinel real-time hospital-based

surveillance www.paeds.edu.au

Australia’s landmark contribution to definining

Intussusception (IS) following new rotavirus vaccines

2007 rotavirus vaccination on NIP

2011 PAEDS Sentinel surveillance – clinically

confirmed cases: comparison with historical ICD-coded

data

2013 Case ascertainment (PAEDS and S/T) 2 sources

Self controlled case series – IRR in risk v. non risk

periods (0-7;0-21 days post vaccination compared with

non risk periods)

2014 No difference in clinical outcomes (vaccine

associated/non vaccine associated)

2016 Trends in hospital-coded IS – temporary increase

in dose 1 age group (1-3 months only)

Buttery, J, Danchin M et al, Vaccine 2011; Quinn, et al, PIDJ 2012; Carlin JB, Macartney K, Lee KJ, et al. Clinical Infectious

Diseases 2013;57:1427-1434; Buttery et al PHAA NIC 2014; Dey, A International Rotavirus meeting 2016, Melbourne.

Methods: Estimates based on method of Patel, et al, NEJM 2011

#: annual number of ICD-coded hospitalisations (data from the Australian Institute of Health and Welfare) for rotavirus AGE and estimated for rotavirus-attributable

AGE (derived from Dey et al, MJA 2012 and Jayasinghe et al, Vaccine 2013). Vaccine effectiveness estimates applied by dose (see appendix).

•derived from using ICD-coded hospitalisations (data from the Australian Institute of Health and Welfare) for IS with adjustment for cases confirmed as IS, vaccine

coverage, age

Annual Hospitalisations

in children < 5 years of

age

Without

vaccination

program

With

vaccination

program

Number of events

averted or caused

Rotavirus attributable

gastroenteritis#

11073 4545 - 6528

Intussusception using

RotaTeq and/or Rotarix* 144 158 14

Effect of a rotavirus vaccination program, as compared with

no rotavirus vaccination program in Australia

Carlin JB, Macartney K, Lee KJ, et al. Clinical Infectious 2013;57:1427-1434.

Conclusions

• Additional 2 cases of IS per 100,000 infants vaccinated

• 14 extra cases above ~ 200 seen annually

• Benefits of vaccination outweigh risks – Australia and internationally

• www.immunise.health.gov.au

2007

• 1 month into program commencement

• 1 school: 26 girls in sick bay post vaccination, 4 to ED

• no organic cause

• prompt thorough response, follow-up, communication

Buttery J et al, MJA 2008; Clements ANZJPH 2007

Key HPV vaccine safety events

Australia

2007 Mass psychogenic illness

Anaphylaxis signal - NSW

2009 Mulitple sclerosis

Injection site adverse events

2013 New vaccine safety plan for

adding males to NIP

2013 Key NCIRS systematic review

Alarming recent declines in

HPV vaccine uptake

overseas

http://globalcancerinstitute.org/health-trends/hpv-vaccine-uptake-latin-america/

Australia:

Vaccine coverage is rising over time National human papillomavirus (HPV) vaccination coverage for girls at age

15, by dose number and year, Australia, 2007–2015

Source: Brotherton et al, Med J Aust 2017 www.hpvregister.org.au/research/coverage-data

Dose 1/2/3 coverage 15 yrs

86/83/78% females

78/75/67% males

14 years in 2015 = higher

87/85/79% females

82/79/74% males

An adult flu shot did this to my boy The Telegraph Sunday November 10, 2013

2010 – Influenza vaccine (Fluvax/CSL) and febrile seizures

0%

10%

20%

30%

40%

50%

60%

WA: Fluvax 2010

Febrile convulsions in 0.5-1% of

children receiving influenza vaccine

National Immunisation Strategy

2013-2018 Horvath review of vaccine adverse

events system 2011

Investigation into influenza vaccine

safety problems

7 Recommendations

including: • Evaluate benefits of additional

surveillance mechanisms to ensure

vaccine safety

• Collection of vaccine usage and safety

monitoring data key priority

www.immunise.health.gov.

au

Strategic Priority 4: Continue to

enhance vaccine safety monitoring

systems • Improve AEFI surveillance

• Vaccine safety plans for NIP

• Raise awareness of safety systems

• Data linkage for vaccine safety

Vaccine Safety plans

New vaccine introduction

Issues specific to

new vaccine

Pre-emptive safety surveillance plan

HPV vaccine

for

males

MMRV vaccine

Horvath review

Influenza vaccine in children

Pertussis vaccines in

children

Zoster vaccine

AUSVAXSAFETY SURVEILLANCE AEFI-CAN

School-based

TGA/JIC

PHREDDS

Febrile

seizures

(PAEDS)

Inappropriate

administration AEFI-CAN

(ELS)

PAEDS (SNE)

• Varicella uptake improved at age 2 years by 4% (from 85.9 to 89.9%)

• On time vaccination for measles-containing vaccine dose 2 increased by 13.5%

• No increased risk of febrile seizures post MMRV vaccine

(used as dose 2 at age 18 months)

Aug 2017

Are alternative vaccines safe? Yes

0%

10%

20%

30%

40%

50%

60%

WA: 2011-2012

0%

10%

20%

30%

40%

50%

60%

WA: Fluvax 2010

0%

10%

20%

30%

40%

50%

60%

WA, NSW, Vic: 2014

0%

10%

20%

30%

40%

50%

60%

WA, NSW, Vic, Qld, SA: 2013

Wood NJ et al MJA 2014; AusVaxSafety report 2014, Blyth et al; Vaccine 2011; Blyth et al, MJA 2011; Markus TY –

unpublished data

AUSVAXSAFETY SURVEILLANCE

What is AusVaxSafety?

Active and novel

Sentinel, routine vaccination

Automated from data extraction from practice software

SMS prompted survey

Patient reported outcomes

All ages

Vaccines: Influenza → Influenza/Pertussis/Zoster → all vaccines

Rapid analysis → weekly, including bayesian signal detection

Real time data

• Vaccine safety

• Vaccine utilisation

• Brand specific

AusVaxSafety: sites and key facts

224 national surveillance sites

~70% response rate at ~3 days

Focus vaccines • Influenza all ages

• Pertussis boosters children

• Zoster

Pillsbury et al, Eurosurveillance 2016

GPs (89%)

Community

Clinics (7%)

Hospitals (4%)

Influenza vaccine safety surveillance 1 April 2017 – 3 September 2017

73,560 participants responded (>100K contacted)

• Median age: 57 years (6 months – 102 years)

• 2% ATSI

• 2.7% pregnant

6.6% event rate

0.4% medical attendance rate

Weekly reporting - No safety signals identified

0123456789

% p

art

icip

an

ts

6 months - 4years5 years - 64years65+ years

NCIRS analysis: Adverse events following immunisation for children aged <1 year, ADRS

database, 2000 to 2016, by quarter of vaccination, by date of vaccination

2017 Australia

NCIRS and

Vaccine safety

State/Territory based AEFI

reporting

Vaccine safety initiatives

TGA national AEFI reporting

Signal investigation support

Clinical Assessment

AEFI-CAN and NSWISS (AusVaxSAfety)

AusVaxSafety

Participant-based active real-time surveillance

Large linked databases

(WA-NSW)

Primary care data analysis

•- MBS encounters GPRN

•- NPS-Medicine Insight

•(With AusVaxSafety)

Sentinel hospital based surveillance

for serious AEFI

(PAEDS)

www.ncirs.usyd.edu.au

THANK YOU to all our leaders, dedicated staff, collaborators and stakeholders and all who prevent disease through immunisation

#NCIRS20YR

Session 4 – Vaccine Communication and Safety – In Australia and

Internationally

Time Topic Speakers and Chairs

3.20 – 4.50 pm Session 4 – Vaccine Communication and Safety – In Australia and Internationally

Chair: Dr Michael Brydon

Chief Executive, The Sydney Children’s

Hospitals Network

3.20 – 3.40 pm Vaccine Hesitancy – An International Perspective Professor Noni MacDonald

3.40 – 4.00 pm Vaccine Communication – Australian and International Lessons Associate Professor Julie Leask

4.00 – 4.20 pm Vaccination in Pregnancy – Effectiveness and Safety Professor Saad Omer

4.20 – 4.40 pm Vaccine Safety – In Australia and Internationally Associate Professor Kristine Macartney

4.40 – 4.50 pm Closing Remarks

Mr David Templeman

President, Public Health Association of

Australia

www.ncirs.usyd.edu.au

#NCIRS20YR