Scope and limitations of registerbased research

Nordic Vaccine Meeting 2014

23rd –25th April in Bergen, Norway

Lill Trogstad, MD, PhD Norwegian Institute of Public Health

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Nasjonalt vaksinasjonsregister, The

Norwgian immunisation reSYSVAK

• National electronic immunisation register, SYSVAK since 1995

– Pilot project 1976 in 5 counties

– Legally based in the SYSVAK-regulation since 2003

– Contains approximately 27 mill. vaccinations for 3,5 mill. persons

– Based on personal identification numbers

The Norwegian immunisation

register- SYSVAK

Trogstad L, Ung G, Hagerup-Jenssen M, Cappelen I, Haugen I, Feiring B. The

Norwegian immunisation register – SYSVAK. Euro Surveill 012;17(16):pii=20147.

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Notification requirements

• All childhood immunisations – Compulsory

• During 2009/2010 pandemic: – All H1N1 vaccinations in children and adults

(approximately 2 mill. vaccinations)

– Compulsory

• Since January 2011: – All vaccinations also in adults included

– Oral consent by vaccinee

• Approximately 1 mill. notifications/ year

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Vaccine registries – utilisation

• Administrative purposes

• Keep track of vaccinations

– Health care personnel’

– Public ‘My vaccines’

• Descriptive studies

• Analytic studies 4

Descriptive studies

• Vaccination coverage

– Time trends

– Geographical variation

– Number of doses (adherence to schedule)

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Examples - descriptive studies

Time series. Proportion of 2-year olds vaccinated in Norway

2000-2013.

http://www.fhi.no/artikler/?id=84900 6

Vaccine coverage (%) MMR, 2013. National data (SYSVAK)

Age Year Measles, mumps,

rubella

2 year olds 2013 93

9 year olds 2013 95

16 year olds 2013 94

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Examples

- descriptive studies

MMR vaccine coverage (%) in 16-year olds, 2013

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Analytic studies

Exposure Vaccination Outcome

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Analytic studies

• Exposures- examples

– Socioeconomic factors

– Chronic diseases

• Outcomes – examples

– Vaccine effectiveness

– Disease burden

– Sero-prevalence/ genotype

alterations

– Adverse events

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Vaccination registries -linkage possibilities for exposures and outcomes

• Other registries

• Cohort studies

• Cross-sectional studies

• Case-control studies

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1. Cause of death registry (personid) 1925/1951

2. Medical Birth Registry (personid) 1967

3. Heart/ coronary disease registry (personid) 2010

4. Reporting system for communicable diseases (MSIS) (personid)

1977

5. TB-registry (personid)

1962

6. Norwegian immunisation register (SYSVAK) (personid) 1995

7. Surveillance system for antibiotic resistance in microbes (NORM) (anonymous)

2003

8. Surveillance system for nosocomial infections (NOIS) (anonymisert) 2005

9. Norwegian prescription database (NorPD)(pseudonymt)

2004

10. Abortion registry (non-identifiable)

1979/2007

11. Norwegian Cancer Registry (personid) 1952

12. Norwegian Patient Registrys (NPR) (personid) 2007

National health registers, Norway

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Vaccination registries

-linkage possibilities for exposures and outcomes

Exposure Exposure

• Population register

• Sosioeconomic register

Vaccination Vaccination

• Vaccination register

Outcomes Outcomes

• Patient register

• Birth register

• Infection register

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Vaccination registries

-linkage possibilities for exposures and outcomes

Exposure

• Cohort study

Vaccination

• Vaccination register

Outcomes

• Cohort study

• Case-control study

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See

poster 15

Examples - analytic studies

Håberg SE et al. N Engl J Med 2013. DOI: 10.1056/NEJMoa1207210.

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Does H1N1 immunisation or infection

cause fetal death?

Exposures Exposures

• Population Registry

• Medical Birth Registry

• Eligible pregnancies

Vaccination and infection Vaccination and infection

• Immunsation Registry

• Vaccination status

• Date of vaccination

• Primary-care data

• Influenza (R80)

• Infection register

• Positive H1N1 tests

Outcomes Outcomes

• Medical Birth Registry

• Fetal death

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Temporal Distribution of Vaccination and Laboratory-Confirmed Pandemic Influenza.

Håberg SE et al. N Engl J Med 2013. DOI: 10.1056/NEJMoa1207210

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Results (1)

• Vaccination during pregnancy not associated with

increased risk of fetal death

– HR: 0.88 (0.66 – 1.17)

• Vaccinated women had reduced risk of influenza

– HR: 0.30 (0.25 – 0.34)

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Results (2)

• Women who were pregnant during the main

pandemic wave had increased risk of fetal death

– HR: 1.26 (1.02 – 1.55)

• Women with a influenza diagnosis had nearly

doubled risk of fetal death

– HR: 1.91 (1.07 – 3.41)

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Is Chronic Fatigue Syndrome/ Myalgic Encephalo-

myelitis (CFS/ME) linked to H1N1 infection or

immunisation ?

Exposure

• Population Registry

• Age

• Sex

Vaccination or infection

• Immunsation Registry

• Vaccination status

• Date of vaccination

• Primary-care data

• Influenza (R80)

• Infection register

• Positive H1N1 tests

Outcomes

• National Patient Register

• CFS/ ME

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Results Table 3. Cumulative incidence of CFS/ME for the years 2010-2012, and

relative risks according to the joint distribution of vaccination and

influenza infection

Vacc Inf#

No of

Subjects

No of

cases

Cum

Incidence *

RR 95 %

CI

No No 2858459 2086 73.0 1 (reference)

Yes No 1804947 1316 72.9 1.00

No Yes 79625 159 200.0 2.74

Yes Yes 36934 63 170.6 2.34

#as reported from primary health care and from microbiology laboratories

*proportion: number of cases per 100,000 subjects 22

Conclusions

• Pandemic influenza A (H1N1) infection

appears to more than double the risk of

CFS/ME

• Immunisation with an inactivated,

adjuvanted influenza vaccine does not

increase the risk

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is linked to pandemic

influenza infection, but not to vaccination. Magnus et al. In prep 2014

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Limitations of registry based

research

• Incomplete notification

– Legal basis

– Technical issues

– Willingness (ability)to notify

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Limitations for analytic studies

• Legal basis

• Opinions of ethical committees

• Completeness and quality of data

• Time and costs

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Prospects

• Increase use of linked registerdata and

analytic methods in the vaccine field in

Norway

• Research purposes

• Systematic surveillance

• Enhance Nordic collaboration for register -

based analyses of rare outcomes

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Thank you

Easter in Southern Norway 2014

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