Immune Response Induced by a Vaccine Against Group B Streptococcus and Safety in Pregnant Women and Their Offsprings: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immune Response Induced by a Vaccine Against Group B Streptococcus and Safety in Pregnant Women and Their Offsprings (NCT01446289), a randomized phase 2 study. The primary outcome is Geometric Mean Concentrations (GMCs) of Antibodies in Mothers and Infants at Delivery/Birth.

2. Clinical Question

3. Trial Design

This was a Phase II, randomized, parallel-group, controlled study of a trivalent Group B Streptococcus vaccine in healthy pregnant women. The official study description identifies it as observer-blind and multicenter. The registry record classifies masking as single, but does not identify who was masked. Participants were assigned to receive one injection of vaccine or one injection of saline solution as placebo. The total enrollment was 86.

The primary endpoint was immunogenicity rather than a clinical disease outcome: antibody geometric mean concentrations against GBS capsular polysaccharide serotypes Ia, Ib and III in mothers and infants at delivery or birth. The defined primary analysis population was the Immunogenicity Per Protocol Set. It included enrolled participants who correctly received the vaccine, had evaluable serum samples at relevant time points and had no major protocol violation as defined before unblinding. The number included in this set is not reported in the registry record.

The registry also lists secondary maternal and infant antibody outcomes, including antibody concentrations and geometric mean ratios, as well as several safety outcomes. These include solicited local and systemic adverse events, unsolicited adverse events, serious adverse events in mothers, and serious adverse events in infants. The listed secondary outcomes extend beyond the primary time point, including infant measurements at 3 months and after routine infant immunization. Numerical results for those immune outcomes are not reported in the registry record.

The record marks the study as completed. It does not report the allocation ratio, the randomization method, the details of the masking procedures, the sample-size justification, or the full statistical analysis plan. The registry record also lists zero analyses. These omissions limit assessment of how the planned comparisons were conducted and how well the analyzed populations correspond to the randomized groups.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 86 pregnant subjects were enrolled in the study. 86 infants were enrolled in this study, delivered by 86 maternal subjects. There were 86 singleton deliveries.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was done on the Immunogenicity Per Protocol Set (PPS), ie: all subjects in the enrolled population who correctly received the vaccine, provided evaluable serum samples at the relevant time points and had no major protocol violation as defined prior to un-blinding.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All enrolled population

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Concentrations (GMCs) of Antibodies in Mothers and Infants at Delivery/Birth, measured over Day of delivery/birth.

The primary endpoint measures geometric mean concentrations of antibodies against GBS capsular polysaccharide serotypes Ia, Ib and III in maternal and infant samples at delivery or birth. Concentrations are expressed in µg/mL, with 95% confidence intervals. The endpoint therefore focuses on the antibody response associated with vaccination and the antibody concentrations present in infants at birth, rather than on whether mothers or infants developed a clinical infection.

A geometric mean is a useful summary when measurements vary multiplicatively or have a right-skewed distribution. In general, it gives a central estimate on a multiplicative scale and can be less influenced by unusually high values than an arithmetic mean. A confidence interval describes the uncertainty around an estimated quantity; its width conveys precision, while its limits indicate values compatible with the analysis under the methods used.

The endpoint is presented separately for mothers and infants and across multiple serotypes. This structure can describe antibody levels in both members of the mother-infant pair and across the specified vaccine targets. However, the registry record does not report numerical GMC estimates or confidence intervals. It therefore does not allow a reader to assess the magnitude, precision or pattern of the primary antibody findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean describe?

A geometric mean summarizes measurements on a multiplicative scale. In general, it is most naturally interpreted as a central value when observations vary by multiplication rather than by equal additive amounts, as can occur with concentration measurements. The primary endpoint uses geometric mean concentrations for antibody measurements against serotypes Ia, Ib and III. This choice describes typical concentration levels without treating each absolute increment as equally meaningful across the measurement range.

The registry record does not specify the transformation, estimation procedure or handling of values below assay limits. Those details are not reported in the registry record. Consequently, the endpoint definition identifies the summary measure, but not every computational choice behind it.

How should the confidence intervals be read?

A 95% confidence interval expresses uncertainty around an estimated quantity under the analysis assumptions. In general, a narrower interval indicates greater precision, whereas a wider interval indicates more uncertainty. For a GMC, the interval provides context for the antibody concentration estimate; for a comparison, an interval would help show the range of effects compatible with the data and model.

The registry record specifies 95% confidence intervals for the primary endpoint, but no primary GMC estimates or interval limits are reported in the registry record. Without the estimates and interval limits, their precision cannot be evaluated. A confidence interval is not a guarantee that a particular value is correct, and it does not replace assessment of the study design or analysis population.

What does randomization contribute?

In general, random assignment is intended to make the study groups comparable at the start, on average, with respect to measured and unmeasured characteristics. It supports a causal interpretation of a between-group comparison when allocation is implemented as planned and the analysis appropriately accounts for the randomized groups. This study is classified as randomized and parallel-group. The specific sequence-generation and allocation-concealment procedures are not reported in the registry record.

The trial is described as observer-blind, and the registry classifies masking as single. Masking can reduce the chance that knowledge of group assignment influences measurements or assessments. The record does not identify which individuals were masked or give procedural details. It is therefore not possible to assess the masking process beyond the classification stated in the registry.

What is the role of the per-protocol population?

The primary analysis population was the Immunogenicity Per Protocol Set. As defined in the registry record, it includes enrolled subjects who correctly received the vaccine, provided evaluable serum samples at relevant times and had no major protocol violation as defined before unblinding. Restricting analysis to participants meeting those conditions can focus attention on measurements obtained under the specified protocol. At the same time, exclusions after enrollment can affect comparability if eligibility for the analysis set is related to group assignment, adherence or outcomes.

The registry record does not report the number of participants in this set, reasons for exclusion, or results from a separate analysis of all randomized participants. It also does not report how missing serum measurements were handled. Those omissions prevent assessment of how much the per-protocol analysis differs from the randomized population.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event planning quantities are expressed as participants per arm. These are planning assumptions, not a report of the trial’s original sample-size justification. The trial’s own sample-size justification is not reported in the registry record.

Any planning illustration based on an observed effect is retrospective and depends on the chosen fraction and assumptions. It should not be read as observed power or as evidence that the trial had a particular probability of detecting an effect. The registry record does not report a protocol-based sample-size calculation or interim-analysis plan.

Why does the endpoint structure matter?

The primary endpoint includes multiple serotypes and two populations, mothers and infants. Such a set of estimates can describe antibody patterns, but it does not automatically define a single treatment comparison. The registry record notes that the primary outcome has several categories or time points and was not reduced to one comparison. No single pooled or selected result should therefore be inferred from the endpoint description.

Multiple outcomes can raise multiplicity concerns when many hypotheses are tested. In general, testing multiple outcomes without an adjustment can increase the chance of at least one apparently unusual result under a collection of null hypotheses. Whether an adjustment is needed depends on the prespecified objectives and analysis strategy. The multiplicity strategy is not reported in the registry record, and no numerical primary tests or analysis results are reported there.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome spans antibody concentrations in mothers and infants and includes serotypes Ia, Ib and III. The registry record indicates that the outcome has several categories or time points and was not reduced to one comparison. It also lists secondary outcomes covering maternal and infant antibody measures and multiple safety outcomes. With several measures, a reader needs to know which comparisons were prespecified as confirmatory and how multiplicity was handled. That strategy is not reported in the registry record.

The registry record lists 10 outcome measures and zero analyses. Numerical primary results and numerical results for the listed immune-response secondary outcomes are not reported in the registry record. The record therefore does not allow reconstruction of the analysis sequence or identification of which estimates were selected for reporting.

The primary analysis population is the Immunogenicity Per Protocol Set, requiring correct receipt, evaluable serum samples at relevant time points and no major protocol violation as defined before unblinding. The size of this set, the number excluded, and reasons for exclusion are not reported in the registry record. The record does not state whether an intention-to-treat analysis was performed or how missing antibody measurements were handled.

These omissions matter because exclusions and missing measurements can affect the population represented by an estimate. They also limit comparison of the per-protocol findings with results among all randomized participants. The sample-size justification, interim-analysis plan and detailed statistical analysis plan are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: premature labour (5.7%), jaundice acholuric (2.9%), cataract congenital (2.9%), ventricular septal defect (2.9%), crying (2.9%).

The safety record gives counts of participants affected within each listed group. For serious adverse events, it reports 7 of 51 mothers in the GBS group and 8 of 35 mothers in the placebo group; among infants, it reports 12 of 51 in the GBS group and 11 of 35 in the placebo group. For other adverse events, the corresponding counts are 35 of 51 and 24 of 35 for mothers, and 0 of 51 and 2 of 35 for infants.

These figures should be read as descriptive group counts. They are not adjusted effect estimates and do not indicate how many events each participant experienced. Counts alone do not establish a causal relationship to the injection. The registry record does not report details needed to interpret event timing, duration of observation, severity classifications beyond the serious-event category, or whether events were judged related to study treatment.

The serious-event term listing gives premature labour at 5.7%, and jaundice acholuric, cataract congenital, ventricular septal defect, crying and appendicitis at 2.9% each. The term listing does not identify the group for each entry. Death counts are not reported in the registry record. These limits mean the listed counts and terms should not be treated as a complete account of comparative safety.

12. What the Result Does, and Does Not, Mean

The study addresses an important measurement question: whether a trivalent GBS vaccine is associated with maternal and infant antibody concentrations at delivery or birth. Its randomized, controlled design sets up a comparison between one vaccine injection and one saline injection. The endpoint focuses on antibody concentrations against serotypes Ia, Ib and III rather than on clinical infections or other health outcomes.

However, the registry record does not report numerical primary GMC results or 95% confidence intervals. It therefore cannot show the estimated level of antibodies in either group, the magnitude or direction of a between-group difference, or how precisely any estimate was measured. The record also does not report numerical results for the listed secondary antibody outcomes.

The safety record contains counts of participants with serious and other adverse events in mothers and infants. Those figures provide descriptive information about participants recorded in each category, but they do not establish that the intervention caused an event or that groups differed in risk. The term listing is not assigned to groups, and the record does not report death counts. Further details about event definitions, follow-up and attribution are not reported in the registry record.

The endpoint’s per-protocol definition identifies a selected analysis population based on receipt, evaluable samples and protocol compliance. Because the size of that population and the missing-data approach are not reported in the registry record, the extent to which the primary analysis represents everyone enrolled cannot be assessed.

Accordingly, the record describes the trial design, planned antibody measurements and some safety counts, but it does not provide the primary numerical evidence needed to characterize the antibody response. It cannot establish clinical benefit or harm, and it does not support medical advice.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a study where the endpoint is an intermediate biological measurement rather than a clinical event. Antibody concentrations can be summarized separately in mothers and infants and by serotype, allowing the study question to address both maternal response and antibody levels in newborns. Geometric means and confidence intervals are appropriate concepts for describing concentration estimates, but the numerical estimates are not reported in the registry record.

The design also highlights how the chosen analysis population affects interpretation. The primary endpoint is defined for a per-protocol set that requires correct receipt, evaluable samples and no major protocol violation. This can make the analysis more closely reflect participants with measurements meeting protocol requirements, while also making the number excluded and reasons for exclusion important. Those details are not reported in the registry record.

Another statistical issue is the multiplicity inherent in several serotypes, two populations and multiple secondary outcomes. Separate estimates may be useful descriptively, but inference requires clarity about which comparisons were prespecified and whether an adjustment strategy was used. That strategy is not reported in the registry record. The absence of numerical primary results further limits assessment of both effect size and precision.

The safety counts illustrate why denominators, event definitions and follow-up context matter. The record gives counts within groups, but does not provide a full comparative analysis or all details needed to interpret those counts. Taken together, the study is a useful case for distinguishing an endpoint’s scientific purpose from the evidence actually available for statistical interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation is that numerical primary endpoint results are not reported in the registry record. Although the primary endpoint is defined as maternal and infant GMCs for serotypes Ia, Ib and III at delivery or birth, the record provides no concentration estimates or 95% confidence intervals. The primary result’s magnitude, direction and precision therefore cannot be assessed.

The registry record lists zero analyses and does not provide numerical results for the listed secondary immune-response outcomes. It also does not report a detailed statistical analysis plan, multiplicity approach, interim-analysis plan or protocol-based sample-size justification. The planning illustration described in the record is based on an observed effect and should not be mistaken for the trial’s original design rationale.

The primary analysis population is a per-protocol set, but its size and the number or characteristics of excluded participants are not reported in the registry record. Missing-data handling and results for all randomized participants are also not reported. These details are necessary to understand how the analytic population may differ from the enrolled population.

Safety information is limited to counts and a list of serious-event terms. The record does not report group assignment for the listed terms, deaths, detailed event definitions, follow-up duration, or treatment attribution. The randomization procedures and identities of those masked are likewise not reported in the registry record. These limitations constrain both the statistical interpretation and the assessment of how the study was conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immune Response Induced by a Vaccine Against Group B Streptococcus and Safety in Pregnant Women and Their Offsprings — NCT01446289.
• Registry record last updated 2014-09-08; status last verified 2014-09.
• Results first posted 2014-09-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed Phase II, randomized, parallel-group, controlled, observer-blind study of a trivalent Group B Streptococcus vaccine in healthy pregnant women. It reports enrollment of 86 participants and compares one vaccine injection with one saline injection. The primary endpoint is maternal and infant geometric mean antibody concentrations against serotypes Ia, Ib and III at delivery or birth, measured in µg/mL with 95% confidence intervals.

The primary analysis population is defined as the Immunogenicity Per Protocol Set. Numerical primary antibody results are not reported in the registry record. The record lists maternal and infant antibody outcomes as secondary measures and reports descriptive serious and other adverse-event counts for mothers and infants. It does not report a detailed analysis plan, multiplicity strategy, missing-data approach or sample-size justification. The available record therefore supports description of the trial design and selected safety counts, but not quantitative interpretation of the primary immunogenicity findings.