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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

Website/Homepagewww.P-95.com

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)

Email address kaatje.bollaerts@p-95.com

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)

Email address kaatje.bollaerts@p-95.com

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.