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Status: Finalised First registered on: 29/06/2016

Last updated on: 24/11/2017

1. Study identification

EU PAS Register NumberEUPAS13908

Official titleADVANCE POC Study Protocol - Testing new approaches to monitoring benefit/risk with pertussis vaccines as test case. Coverage rates of acellular and whole-cell pertussis-containing vaccines in preschool children

Study title acronymADVANCE Coverage POC

Study typeObservational study

Brief description of the studyThe overall ADVANCE proof-of-concept (POC) question is to test the system for benefit-risk monitoring of vaccines in Europe. This will first be done by using test cases. For this POC, the following research question is used: “Has the initial benefit-risk profile in children prior to school-entry booster been maintained after the switch from whole-cell pertussis vaccines to acellular pertussis vaccines”?

Was this study requested by a regulator?No

Is the study required by a Risk Management Plan (RMP)? Not applicable

Regulatory procedure number (RMP Category 1 and 2 studies only)

Other study registration identification numbers and URLs as applicable

2. Research centres and Investigator details

Coordinating study entity

Centre nameStatens Serum Institut

Centre locationArtillerivej 5, 2300 Copenhagen, Denmark

Details of (Primary) lead investigator

Title Dr

Last name Emborg

First name Hanne-Dorthe

Is this study being carried out with the collaboration of a research network?

Yes

ADVANCE

Other centres where this study is being conducted

Multiple centres

In total how many centres are involved in this Study?7

IDIAPJGol

ARS

Erasmus MC Pharmacoepi

THIN, UK

FISABIO, Spain

BIFAP, spain

SSI, Denmark

Countries in which this study is being conducted

International study

Denmark

Italy

Spain

United Kingdom

3. Study timelines: initial administrative steps, progress reports and final report

PlannedActual

Date when funding contract was signed01/10/201301/10/2013

Start date of data collection01/06/201601/06/2016

Start date of data analysis

Date of interim report, if expected

Date of final study report15/09/201629/06/2016

4. Sources of funding

Please provide estimates of the percentage of funding by source for this study

Names(s)Approximate % funding

Pharmaceutical companiesGSK, SP, NOVARTIS, SP MSD, CRUCELL, PFIZER, TAKEDA50

Charities

Government body

Research councils

EU funding scheme

OtherIMI50

5. Contact details for enquiries

Scientific Enquiries

Title Dr

Last name Emborg

First name Hanne-Dorthe

Address line 1Artillerivej 5

Address line 2

Address line 3

CityCopenhagen

Postcode2300

CountryDenmark

Phone number (incl. country code)45-32683937

Alternative phone number

Fax number (incl. country code)

Email address hde@ssi.dk

Public Enquiries

Title Dr

Last name Emborg

First name Hanne-Dorthe

Address line 1Artillerivej 5

Address line 2

Address line 3

CityCopenhagen

Postcode2300

CountryDenmark

Phone number (incl. country code)45-32683937

Alternative phone number

Fax number (incl. country code)

Email address hde@ssi.dk

11. Scope of the study

What is the scope of the study?

Coverage study

Primary scope : Coverage study

12. Main objective(s)

What is the main objective of the study?

To estimate the coverage of pertussis-containing vaccines in children less than 6 years of age. The specific objective of this study is to assess the system capability to estimate acellular pertussis and whole-cell pertussis vaccine coverage

Are there primary outcomes?Yes

Coverage rate overall and for wP and aP vaccines is the proportion of vaccinated children by database, birth cohort, age in months and per dose The variability of vaccine administration is defined as the time elapsed between birth and the first dose and the time elapsed between subsequent scheduled doses. Changes of coverage rates over time will be described by general descriptive statistic

Are there secondary outcomes?No

13. Study design

What is the design of the study?

retrospective population based cohort study

14. Follow-up of patients

Will patients be followed up?Not applicable/no follow-up

15. Data analysis plan

Please provide a brief summary of the analysis method

• The coverage by age in months per birth cohort will be calculated using a Kaplan-Meier method. The proportion of vaccinated children with dose 1, 2, 3, and subsequent boosters will be calculated stratified by year of birth, type of vaccine and database. • The change of coverage rates over time will be calculated by the difference between coverage rates and a defined threshold. Low coverage thresholds will be determined for identification of variability of interest/concern. Data-driven thresholds will be compared with set values based on coverage rates required for herd immunity. CUSUM involves the calculation of a cumulative sum (which is what makes it ‘sequential’). It is designed to detect changes in the difference. It differs from Sequential Probability Ratio Test (SPRT) by always using zero function as the lower ‘holding barrier’. Also, CUSUM does not require the use of the likelihood function.