Status: Finalised
First registered on:
06/07/2016
Last updated on:
02/09/2019
1. Study identification
EU PAS Register NumberEUPAS13978
Official titleADVANCE POC I Benefit-Risk pillar – testing new approaches to monitoring benefit/risk with pertussis vaccines as test case: benefit-risk analysis of pertussis vaccines in pre-school children comparing whole-cell and acellular formulations in the post-marketing setting
Study title acronymADVANCE POC I Benefit-Risk
Study typeOther: proof of concept feasibility 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?”
The objectives of this specific benefit-risk modelling exercise, which focuses on testing methods for benefit-risk analysis with pertussis vaccines as test case, are the following:
1. To analyze the benefit-risk balance of pertussis-containing vaccines in children comparing wP and aP formulations at the time of the switch from wP to aP adopting a public health perspective (historical benefit-risk)
2. To investigate the impact of (1) statistical uncertainty in benefit and risk estimates as obtained from the literature, clinical trials, observational databases (uncertainty analyses), (2) differences in preferences and (3) subjective model choices (scenario analyses).
3. To identify the benefit and risk criteria that would most likely modify the benefit-risk balance in case they would change over time (i.e. the pivotal parameters).
4. To assess the feasibility of (retrospectively) monitoring the benefit-risk balance of pertussis-containing vaccines over time (this to mimic prospective monitoring)
5. To re-analyze the benefit-risk balance of pertussis-containing vaccines in children comparing wP and aP formulations from a public health perspective using all currently available evidence (current assessment).
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 to which the investigator belongsP95
Department/Research group
Organisation/affiliationP95
Details of (Primary) lead investigator
Title Dr
Last name Bollaerts
First name Kaat
Is this study being carried out with the collaboration of a research network?
Yes
ADVANCE
Other centres where this study is being conducted
Not applicable (single centre)
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 analysis01/09/201601/09/2016
Date of interim report, if expected30/04/2017
Date of final study report01/02/201730/07/2017
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 Bollaerts
First name Kaat
Address line 1Koning Leopold III laan 1
Address line 2
Address line 3
CityLeuven
Postcode3001
CountryBelgium
Phone number (incl. country code)32-485789657
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Bollaerts
First name Kaat
Address line 1Koning Leopold III laan 1
Address line 2
Address line 3
CityLeuven
Postcode3001
CountryBelgium
Phone number (incl. country code)32-485789657
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Single-Constituent (Substance INN)ACELLULAR PERTUSSIS VACCINE
Single-Constituent (Substance INN)PERTUSSIS, INACTIVATED, WHOLE CELL, COMBINATIONS WITH TOXOIDS
7. Medical conditions to be studied
Medical condition(s)Yes
Injection related reaction
Somnolence
Crying
Convulsion in childhood
Lip swelling
Pertussis
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 subjects1
Additional information
not applicable
10. Source of data
Is this study being carried out with an established data source?No
Sources of data
not applicable
11. Scope of the study
What is the scope of the study?
benefit-risk modeling
Primary scope : benefit-risk modeling
12. Main objective(s)
What is the main objective of the study?
1.Analyze the benefit-risk of pertussis vaccines in children comparing wP and aP at the time of switch from wP to aP (historical)
2.Investigate the impact of uncertainty in benefits, risks and preferences
3.Identify the criteria that most likely modify the benefit-risk
4.Assess the feasibility of monitoring benefit-risk over time
5.Re-analyze the benefit-risk using currently available evidence
Are there primary outcomes?Yes
Exposure of interest: any whole-cell and acellular pertussis-containing vaccines and their doses in the vaccine schedule
Outcomes:
Injection site reactions, fever, somnolence, persistent crying, generalized convulsive seizures, HHE, extensive limb swelling, pertussis, pertussis related death
Are there secondary outcomes?No
13. Study design
What is the design of the study?
cohort state transition model, MCDA
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 benefit-risk assessments will be carried out following the Multi-Criteria Decision Analyses (MCDA) methodology. MCDA is a quantitative methodology for appraising alternatives on individual, often conflicting criteria and combining them into one overall appraisal, through incorporating elicited preferences (weights). The preferences will be elicited using MCDA-swing weighting. In addition, several sensitivity analyses will be conducted to investigate the impact of uncertainty in the benefits, risks and preference estimations on the overall benefit-risk balance. A state transition model will be build to generate the effects table, which will be used for the MCDA swing weighting.
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
