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
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)
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)
6. Study drug(s) information
Multi-Constituent (Substance INN(s))PERTUSSIS, INACTIVATED, WHOLE CELL, COMBINATIONS WITH TOXOIDS
ACELLULAR PERTUSSIS VACCINE
7. Medical conditions to be studied
Medical condition(s)No
8. Population under study
Age
Infants and toddlers (28 days - 23 months)
Children (2 - 11 years)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects10000000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Data sources not registered with ENCePP
FISABIO, Spain
National registers, Denmark
Sources of data
Administrative database, e.g. claims database
Routine primary care electronic patient registry
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.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
