The immunogenicity and sero-efficacy of pneumococcal vaccines

Lead Investigator: Merryn Voysey, University of Oxford
Title of Proposed Research: The immunogenicity and sero-efficacy of pneumococcal vaccines
Vivli Data Request: 4120
Funding Source: Government Funding – UK National Institute of Health Research, Health Technology Assessment Programme (HTA 17.148.03,PI: M.VOYSEY)
Potential Conflicts of Interest: None.

Summary of the Proposed Research:

Decisions about which vaccines to use should be made based on good data to make sure the population is well protected against disease.

Pneumococcal disease is a serious illness caused by a bacterial infection that can result in death. Children in the UK receive one type of pneumococcal vaccine to prevent this disease and the vaccine in use has been very successful. Another vaccine is used in other countries, and might be a good option for the UK. From studies in this area, however, there is very little information directly comparing vaccines, so it is difficult to know which is best.
We plan to do a large analysis combining data from multiple pneumococcal vaccine studies in a ‘meta-analysis’. We will conduct a meta-analysis of Pfizer studies that directly compared licensed pneumococcal vaccines in randomised head-to-head trials. The primary outcome will be antibody levels measured 4- 6 weeks after vaccination.
We aim to show which vaccine produces the highest responses when measured in blood samples in infants and also to show which vaccine protects infants best against infection.

Our results will provide the best comparison of pneumococcal vaccines done so far. This will help the policy-makers to decide whether to keep the current vaccine or to change. In turn, this will help to continue to protect the population against disease.

Statistical Analysis Plan:

Meta-analysis of immunogenicity

 

We will conduct a meta-analysis of studies that directly compared licensed pneumococcal vaccines to compare immunogenicity of vaccine serotypes. The primary outcome will be antibody levels measured 4- 6 weeks after vaccination.

Meta-analyses will be conducted for each serotype and each time point (e.g. at 4 weeks post-primary or 4 weeks post-booster vaccine) separately.

Each trial that has individual participant data available will be analysed separately using the online Vivli portal. Geometric mean ratios and standard errors will be computed for each serotype and time point of interest separately for each trial and each vaccine comparison.

Trial-specific estimates and standard errors will be exported and saved into an offline database and used to conduct the meta-analysis. If individual participant data are unavailable for some studies, published estimates and standard errors may be included where applicable.

 

Meta-analysis of sero-efficacy

 

We will conduct a second set of meta-analyses in a similar way as the comparison of immunogenicity, but the outcome of interest will instead be sero-efficacy. For each participant we will define their recent infection status from their antibody data. This will be a binary variable equivalent to 1 if antibody levels have increased between the one-month post-primary time point and the booster visit, or 0 otherwise. During this time period antibody levels typically decline substantially, therefore when antibody increases instead of declining sharply, it is evidence of exposure to the bacteria in the intervening period. Binary data can then be compared between vaccine groups to estimate odds ratios with corresponding standard errors. This will be done for each serotype for each trial separately. These estimates will then be exported and meta-analysed.

Requested Studies

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND, TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATION IN FRANCE
Data Contributor: Pfizer Inc.
Study ID: NCT00366678 / B1851091

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN CANADA
Data Contributor: Pfizer Inc.
Study ID: NCT00475033 / B1851008

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN BRAZIL
Data Contributor: Pfizer Inc.
Study ID: NCT00676091 / B1851003

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN THE UNITED KINGDOM
Data Contributor: Pfizer Inc.
Study ID: NCT00384059 / B1851090

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 3 LOTS OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN THE UNITED STATES
Data Contributor: Pfizer Inc.
Study ID: NCT00444457 / B1851006

A PHASE 2, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN KOREA
Data Contributor: Pfizer Inc.
Study ID: NCT00689351 / B1851001

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY AND IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATION IN TAIWAN
Data Contributor: Pfizer Inc.
Study ID: NCT00688870 / B1851005

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOLOGIC NONINFERIORITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE COMPARED TO A 7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN THE UNITED STATES
Data Contributor: Pfizer Inc.
Study ID: NCT00373958 / B1851101

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN ITALY
Data Contributor: Pfizer Inc.
Study ID: NCT00366899 / B1851096

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL OF THE SAFETY, TOLERABILITY, AND IMMUNOLOGIC NONINFERIORITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE COMPARED TO A 7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN IN A 2-, 3-, 4-, AND 11- TO 12-MONTH SCHEDULE WITH ROUTINE PEDIATRIC VACCINATIONS
Data Contributor: Pfizer Inc.
Study ID: NCT00366340 / B1851089

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN WITH DTAP COMPARED TO OPEN-LABEL DTAP IN HEALTHY JAPANESE INFANTS
Data Contributor: Pfizer Inc.
Study ID: NCT01200368 / B1851056

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13VPNC COMPARED WITH A 7VPNC IN HEALTHY INFANTS IN CHINA
Data Contributor: Pfizer Inc.
Study ID: NCT01692886 / B1851015

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH A MENINGOCOCCAL C-TETANUS TOXOID CONJUGATEVACCINE AND OTHER ROUTINE PEDIATRIC VACCINATIONS IN SPAIN.
Data Contributor: Pfizer Inc.
Study ID: NCT00474539 / B1851095

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN INDIA
Data Contributor: Pfizer Inc.
Study ID: NCT00452790 / B1851002

A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE MANUFACTURED WITH AND WITHOUT POLYSORBATE 80 IN HEALTHY INFANTS GIVEN IN A 2-, 3-, 4-, AND 12-MONTH SCHEDULE WITH ROUTINE PEDIATRIC VACCINATIONS
Data Contributor: Pfizer Inc.
Study ID: NCT00366548 / B1851092

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, DOUBLE-BLIND TRIAL EVALUATING THE IMPACT OF A 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE ON NASOPHARYNGEAL COLONIZATION WITH VACCINE SEROTYPES OF S PNEUMONIAE IN HEALTHY INFANTS IN ISRAEL
Data Contributor: Pfizer Inc.
Study ID: NCT00508742 / B1851007

Public Disclosures:

Shuo Feng, Julian Higgins, Maria Knoll, Julie Mclellan, Kim Muholland, Nicola Pidduck, Andrew Pollard, Beth Temple, Merryn Voysey. COMPARISON OF IMMUNOGENICITY AND SEROEFFICACY BETWEEN TEN- AND THIRTEEN-VALENT PNEUMOCOCCAL CONJUGATE VACCINES – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS. ESPID-2022-Abstracts-Book. Page 294 PD103 / #743.