Status: Finalised
First registered on:
14/06/2016
Last updated on:
22/11/2017
1. Study identification
EU PAS Register NumberEUPAS13779
Official titleADVANCE POC I Risk pillar - Testing new approaches to monitoring benefit/risk with pertussis vaccines as test case: Incidence rates of safety outcomes of whole-cell pertussis and acellular pertussis vaccines in pre-school children
Study title acronymADVANCE POC I Risk
Study typeOther: Proof of concept feasibiliy study
Brief description of the studyRATIONALE: The ADVANCE proof-of-concept (POC) question is to test the system for benefit-risk monitoring of vaccines in Europe. For this POC feasibility study, the research question “Has the initial benefit-risk profile in children prior to school-entry booster been maintained after the switch from whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines?” is used.
OBJECTIVES:
1. To evaluate participating databases on quality criteria for inclusion in the study.
2. To provide incidence rates of specific events (i.e. injection site reactions, fever, somnolence, persistent crying, irritability, febrile or afebrile seizure/convulsion, hypotonic-hyporesponsive episode [HHE], extensive limb swelling) within risk periods after each dose of wP or aP vaccine and within the periods outside the risk windows (baseline) in pre-school children for a benefit/risk analysis model.
3. To provide calendar time specific incidence data as test for methods development in ADVANCE WP4.
STUDY DESIGN: is a retrospective dynamic cohort study.
The study will be conducted utilizing electronic health care data from ADVANCE partners in different European countries
POPULATION: The study population will comprise all children registered in any of the participating databases during the study period and for whom an adequate start and end of follow-up and date of birth can be defined.
Children will be followed from start of the study period, one month after date of birth, or date of valid data in the database (whichever is the latest) until the end of study period (31-12-2015, the school-entry pertussis booster, transferring out of the database, death, reaching age 6 years: whichever is the earliest).
Data Analysis: incidence rates (i.e. baseline and risk-window specific) of known adverse reactions following vaccination with pertussis-containing vaccines for use in a multi-criteria decision analysis (MCDA) model of benefits and risks of wP versus aP 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
Department/Research groupPharmacoepidemiology Erasmus University
Organisation/affiliationErasmus University Medical Center
Details of (Primary) lead investigator
Title Dr
Last name Weibel
First name Daniel
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?6
SSI, Denmark
BIFAP, Spain
FISABIO, Spain
THIN, UK
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 report01/06/201617/08/2017
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government body
Research councils
EU funding schemeIMI100
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Weibel
First name Daniel
Address line 1POBOX 2040
Address line 2dep. Medical Informatics
Address line 3
CityRotterdam
Postcode3000 CA
CountryNetherlands
Phone number (incl. country code)31107037889
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Weibel
First name Daniel
Address line 1POBOX 2040
Address line 2dep. Medical Informatics
Address line 3
CityRotterdam
Postcode3000 CA
CountryNetherlands
Phone number (incl. country code)31107037889
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Single-Constituent (Substance INN)PERTUSSIS, INACTIVATED, WHOLE CELL, COMBINATIONS WITH TOXOIDS
Single-Constituent (Substance INN)ACELLULAR PERTUSSIS VACCINE
7. Medical conditions to be studied
Medical condition(s)Yes
Injection related reaction
Somnolence
Crying
Convulsion in childhood
Lip swelling
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
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?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
1. To evaluate participating databases on quality criteria for inclusion in the study
2. To provide incidence rates within specific risk windows after each dose of wP or aP vaccine in pre-school children and within the periods outside the risk windows (baseline) for a benefit/risk analysis model
3. To provide calendar time specific incidence data as test for methods development in ADVANCE WP4.
Are there primary outcomes?Yes
Exposure of interest
Any wP vaccines and aP pertussis-containing vaccines and their doses in the vaccine schedule (D1, D2, D3, D4, D5)
Outcomes
Injection site reactions: erythema, edema, induration/nodule/sterile abscess, pain/tenderness
Fever
Somnolence
Persistent crying, irritability
Generalized convulsive seizures
HHE
Extensive limb swelling
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Children will be followed from start of the study period, one month after date of birth or date of valid data in the database (whichever is the latest) until the end of study period (31-12-2015, the school-entry pertussis booster, transferring out of the database, death, reaching age 6 years: whichever is the earliest).
15. Data analysis plan
Please provide a brief summary of the analysis method
Data Analysis: The purpose of this study is to provide incidence rates (i.e. baseline and risk-window specific) of known adverse reactions following vaccination with pertussis-containing vaccines for use in a multi-criteria decision analysis (MCDA) model of benefits and risks of wP versus aP pertussis vaccines (models are described in a separate benefit-risk study protocol). In some more recent databases, wP information will not be captured. To generate risk-window specific incidence rates for the wP period in these databases, the IR ratio originating from an SCCS analysis of wP versus baseline in other databases will be multiplied by the baseline IR.
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 documents
DescriptionDocumentLatest version
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
