Extension Study to Evaluate the Immunogenicity and Safety of the Second Dose of GBS Trivalent Vaccine in Healthy Non-Pregnant Subjects.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study to Evaluate the Immunogenicity and Safety of the Second Dose of GBS Trivalent Vaccine in Healthy Non-Pregnant Subjects. (NCT02690181), a non-randomized phase 2 study. The primary outcome is Percentage of Subjects With ELISA Antibody Concentrations of GBS Serotype Ia Above Pre-specified Thresholds - Day 61.

2. Clinical Question

3. Trial Design

This was a Phase 2, non-randomized, controlled, open-label, parallel-group extension study. The registry lists enrollment of 80. The study began on 2016-03-29, had primary completion on 2016-11-02, and is listed as completed. GlaxoSmithKline is the sponsor.

The extension evaluated a single dose of unadjuvanted GBS Trivalent Vaccine. Participants were grouped according to their parent-study treatment history: unadjuvanted vaccine, alum-adjuvanted vaccine, full-dose MF59, half-dose MF59, placebo, or no previous GBS vaccination. The first five histories relate to parent study V98 06; the extension is identified as V98 06E1. The naive group had no prior GBS vaccination. Every group description specifies receipt of unadjuvanted vaccine in this extension.

The non-randomized structure matters for interpretation. Group membership partly reflects earlier vaccine or placebo exposure, rather than assignment to comparable groups at the start of the extension. Differences between group outcomes, if reported, could therefore reflect prior treatment history or other group differences, as well as response to the extension dose. The registry specifically cautions that the arms are not a like-for-like control comparison.

The study is open-label, with no masking. The registry record does not report the interval between doses, detailed eligibility criteria for all groups, or procedures used to assign participants to groups. It also does not report a protocol-based sample-size justification or interim-analysis plan. These details cannot be inferred from the extension's stated objective.

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: All enrolled subjects completed the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All screened subjects who provided informed consent and baseline screening measurements, received a subject ID, received study vaccine according to the protocol, and parent study vaccine (non-naïve subjects), and provided immunogenicity data at Day 1, Day 31 or Day 61 in this study.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With ELISA Antibody Concentrations of GBS Serotype Ia Above Pre-specified Thresholds - Day 61, measured over At Day 61.

The primary endpoint is the percentage of subjects with ELISA antibody concentrations for GBS serotype Ia above pre-specified thresholds at Day 61. The endpoint description specifies sequential serotype-specific serum antibody levels. It is therefore a threshold-based binary outcome at the participant level: a subject either reaches the defined threshold sequence or does not, according to the endpoint definition.

Antibody concentrations measured by ELISA provide a laboratory measure of the immune response. Reporting the percentage above thresholds expresses how often participants attained the specified response criteria, rather than reporting only a group average concentration. The registry also lists secondary outcomes for antibody thresholds and geometric mean antibody concentrations for serotypes Ia, Ib and III, including selected analyses among participants whose prevaccination antibody was below the lower limit of quantitation.

The registry record does not report the numerical antibody thresholds, the observed primary percentage, or its 95% confidence interval. It also does not state the biological or clinical basis for selecting the thresholds. Consequently, the endpoint definition can be described, but the magnitude and precision of the observed response cannot be assessed from the registry information recorded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is binary at the subject level: the primary definition classifies whether a participant reached the pre-defined sequence of serotype Ia antibody levels at Day 61. The outcome is expressed as a percentage of subjects. This is different from a continuous antibody concentration, which can take a range of measured values and is also represented among the listed secondary outcomes by geometric mean concentrations.

What does a confidence interval communicate?

A confidence interval describes uncertainty around an estimated quantity, such as a percentage. It reflects the fact that an estimate from participants in a study may vary from the value that would be observed in a broader population under comparable conditions. A narrower interval indicates greater statistical precision than a wider interval, but precision alone does not establish clinical importance or eliminate design limitations. The registry identifies a 95% confidence interval as the primary endpoint's dispersion measure, but does not report the interval or the underlying estimate.

For a percentage endpoint, uncertainty is influenced by how many participants contribute data and how many meet the endpoint. In general, fewer observations yield less precise estimates, particularly when the outcome is uncommon or very common. This is a general statistical explanation; the registry record does not give the endpoint-specific denominator or number meeting the threshold. The overall enrollment figure cannot substitute for those details because not every enrolled participant is necessarily part of the primary analysis population.

How should the groups be compared?

The study is non-randomized and open-label, and group membership is tied to parent-study history. Random allocation is commonly used to balance measured and unmeasured characteristics between groups, on average. That protection is absent when participants enter groups through prior exposure history. Differences in antibody measurements could reflect those histories or other differences between the participants, not only the extension vaccination. The registry warns that the arms are not a like-for-like control comparison, so group contrasts should be read descriptively rather than as randomized treatment effects.

The primary measure is a percentage meeting antibody thresholds, while secondary measures include geometric mean concentrations. A geometric mean is a way of summarizing measurements that are positive and may be skewed, often by averaging on a logarithmic scale and returning to the original scale. That is a general description; the exact transformation, handling of values below quantitation limits, and calculation procedures are not reported in the registry record. The endpoint list identifies analyses for some subjects with prevaccination antibody below the lower limit of quantitation, but does not specify the detailed statistical method.

What can sample-size illustrations tell readers?

Sample-size illustrations based on an observed effect are planning exercises, not observed evidence about how likely the study was to detect a result. The registry's stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations depend on assumptions and do not replace a design justification. The registry does not report that these assumptions were used to plan the trial, nor does it report a protocol sample-size justification. Any illustrated sample size should be read as a hypothetical planning quantity, not as the study's actual enrollment target or observed power.

Over-dispersion is a general concern when outcomes vary more than a simple statistical model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The primary outcome is a participant-level binary percentage, but the registry record does not describe an over-dispersion assessment or a model for the endpoint. It would therefore be inappropriate to state that a particular method was used or that this issue affected the results.

Likewise, statistical significance and estimation answer different questions. A significance test assesses compatibility of data with a specified null hypothesis under model assumptions; an estimate and confidence interval describe effect size and precision. No primary estimate, interval, or test result is reported in the registry record, so none can be interpreted. The outcome definition and confidence-interval label alone do not establish whether the endpoint was met.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple immunogenicity outcomes, including threshold-based percentages for serotypes Ia, Ib and III, geometric mean antibody concentrations, and measures in selected participants with low prevaccination antibody. It reports 19 outcome measures in total. When several outcomes or time points are examined, the chance of at least one apparently notable result can increase if each is tested separately without adjustment. This is a general statistical issue; the registry record does not report whether multiplicity was addressed or which outcomes, if any, were designated for formal hypothesis testing beyond identifying the primary endpoint.

Missing-data handling is also important for percentages and antibody summaries. The primary endpoint population is defined as screened subjects who met specified study participation and vaccination conditions and had immunogenicity data at Day 1, Day 31 or Day 61. The record does not report how missing Day 61 measurements were handled, whether participants with incomplete measurements were excluded, or whether any imputation or sensitivity analysis was performed. It does not report endpoint-specific denominators or reasons for missing data.

The registry record does not describe the statistical analysis plan, analysis populations beyond the primary population definition, interim analyses, or adjustment for baseline measurements and other covariates. It lists zero analyses. These omissions mean readers cannot determine which statistical procedures were prespecified or how deviations, if any, were handled. A completed study status does not supply this information, and absence of a reported analysis should not be interpreted as evidence that a particular method was or was not used.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts by group. In the GBS NoAdj/GBS NoAdj, GBS Alum/GBS NoAdj, GBS MF59 Half/GBS NoAdj, GBS MF59 Full/GBS NoAdj, Placebo/GBS NoAdj and Naive/GBS NoAdj groups, the respective numbers at risk were 14, 14, 15, 10, 6 and 21. The number with a serious adverse event was 0 in every group. Deaths were also 0 in every group.

For other adverse events, the reported counts were 13 of 14, 13 of 14, 13 of 15, 7 of 10, 4 of 6 and 17 of 21, respectively. These are participant counts, not counts of individual events. The registry record does not give event terms, severity, relatedness, duration, or the observation period for these other adverse events in the listed information.

Zero reported serious events means none were recorded among the participants at risk in these groups; it does not establish that the risk is absent. The groups are non-randomized and differ in size and prior vaccination history, so these counts do not support a like-for-like safety comparison. The record lists no top serious event terms.

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

This study was designed to make an initial assessment of safety and immunogenicity after a second dose of GBS Trivalent Vaccine, with the extension dose unadjuvanted. Its primary endpoint is a Day 61 antibody-threshold percentage for serotype Ia. The available registry information establishes how the endpoint was defined and identifies the planned measure of uncertainty, but it does not report the observed percentage or confidence interval. Therefore, it does not support a conclusion about the size or precision of the measured antibody response.

The recorded safety information reports zero serious adverse events and zero deaths in each listed group, alongside counts of participants with other adverse events. Those counts describe what was recorded in the groups; they do not show that adverse events were caused by the vaccine or establish a comparative safety effect. The detail needed to characterize the other events is not reported in the registry record.

The study's non-randomized, open-label structure further limits causal interpretation. Group histories differ because participants had received different treatments, placebo, or no GBS vaccine in the parent study. Every group received unadjuvanted vaccine in the extension. Comparisons across these groups cannot isolate the effect of prior formulations or function as randomized comparisons.

The registry record also does not report the antibody thresholds, detailed statistical analysis methods, handling of missing measurements, multiplicity procedures, or a protocol-based sample-size justification. These omissions do not mean that such procedures were absent; they mean the record does not document them. The appropriate reading is consequently bounded: the record describes the trial question, group structure, endpoint and safety counts, while leaving the primary immunogenicity result and its uncertainty unreported.

13. Why This Trial Matters Statistically

Statistically, this extension is notable because its groups encode treatment history rather than a newly randomized assignment. That distinction affects the meaning of any apparent difference. A comparison between participants previously exposed to different formulations and participants who were naive or previously received placebo can describe observed patterns, but cannot by itself separate the contribution of prior exposure from other differences between groups.

The primary endpoint also illustrates the difference between a laboratory measurement and a clinically interpreted outcome. The endpoint converts measured serotype Ia antibody concentrations into a percentage meeting pre-defined thresholds. The record does not state the cutoff values or their clinical basis, nor does it report the resulting percentage. Readers can identify what was measured, but cannot evaluate the observed response or the practical meaning of crossing the threshold.

The 95% confidence-interval label signals that uncertainty was intended to accompany the percentage estimate. That is important because a point estimate alone can conceal how variable or imprecise an estimate may be. Here, the numerical estimate and interval are not reported in the registry record, so their statistical precision cannot be assessed.

The trial also has multiple immunogenicity outcomes, covering three serotypes, threshold percentages and geometric mean concentrations. Such breadth can provide different views of antibody response, while raising questions about multiplicity, endpoint hierarchy and selective emphasis. The registry record does not report the relevant adjustment or analysis plan. The case therefore underscores why outcome definitions, denominators, estimation methods and uncertainty should accompany reported findings, especially in a non-randomized extension study.

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 largest limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. Neither the percentage meeting the Day 61 serotype Ia threshold criterion nor its 95% confidence interval is available in the recorded details. The threshold values themselves are also not reported, so the criterion cannot be independently characterized.

Non-randomized allocation and open-label conduct constrain comparisons. Participants entered groups according to prior study history, and those histories were not alike. Although the extension groups all received unadjuvanted vaccine, differences between groups would not be attributable to the extension dose alone. The registry explicitly cautions that the arms are not a like-for-like control comparison.

The enrollment figure is 80, but endpoint-specific denominators and the number analyzed for immunogenicity are not reported. The primary population description requires immunogenicity data at Day 1, Day 31 or Day 61, but the record does not detail the handling of missing Day 61 data. The statistical analysis plan, multiplicity procedures, interim-analysis plan, and sample-size justification are not reported in the registry record.

For safety, serious events and deaths are reported as zero across groups, but the record does not give further detail about other adverse events, including event terms or severity. The non-randomized group structure and limited group sizes also restrict what can be inferred from descriptive counts. These limitations concern interpretation of the registry record and should not be mistaken for evidence that unreported procedures or data do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extension Study to Evaluate the Immunogenicity and Safety of the Second Dose of GBS Trivalent Vaccine in Healthy Non-Pregnant Subjects. — NCT02690181.
• Registry record last updated 2024-04-04; status last verified 2024-03.
• Results first posted 2018-07-16.
• 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

NCT02690181 is a completed Phase 2, non-randomized, controlled, open-label, parallel-group extension study sponsored by GlaxoSmithKline. It lists enrollment of 80 and evaluates a single dose of unadjuvanted GBS Trivalent Vaccine in groups defined by parent-study history or no prior GBS vaccination.

The primary endpoint is the percentage of subjects reaching pre-defined sequential antibody levels for GBS serotype Ia at Day 61 by ELISA, with a 95% confidence interval specified as the dispersion measure. The registry lists 19 outcome measures and zero analyses. It does not report the primary endpoint estimate, interval, threshold values, detailed analysis plan, or missing-data procedures.

Serious adverse events and deaths are reported as zero in all six groups. Counts of participants with other adverse events are recorded, but event details are not included in the available safety information. The registry cautions that the non-randomized groups are not a like-for-like control comparison.