A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF A GROUP B STREPTOCOCCUS 6 VALENT POLYSACCHARIDE CONJUGATE VACCINE (GBS6) IN HEALTHY ADULTS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF A GROUP B STREPTOCOCCUS 6 VALENT POLYSACCHARIDE CONJUGATE VACCINE (GBS6) IN HEALTHY ADULTS (NCT04258995), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Reporting Prompted Local Reactions Within 14 Days Following Booster Dose (Redness, Swelling, and Pain at the Injection Site).

2. Clinical Question

3. Trial Design

This is a Phase 2, open-label, non-randomized, parallel-group trial of a GBS6 booster in healthy adults. The registry lists Pfizer as the sponsor and enrollment of 151 participants. The study is marked completed. It began on 2020-02-11, and its primary completion date is 2020-09-15.

The study is described as an extension to a completed first-in-human study. Participants had received a primary GBS6 dose, and the booster was to be given approximately 2 years or more later. The stated purpose was to evaluate safety and immunogenicity after a single booster dose and determine whether individuals who had received a primary dose had additional benefit following boosting. That statement describes the study’s aim, not a result.

The registry lists two groups: GBS6 20 μg with aluminum phosphate and GBS6 20 μg without aluminum phosphate. Allocation is recorded as non-randomized and masking as none; the model is parallel. Because treatment assignment was not randomized, observed differences between groups cannot be interpreted as if the groups were necessarily comparable at baseline. The registry explicitly cautions that the arms are not a like-for-like control comparison. The basis for assignment, and any additional information needed to assess comparability, is not reported in the registry record.

The primary endpoint concerns prompted local reactions during the 14 days after vaccination. Secondary outcomes cover serotype-specific IgG geometric mean concentrations, opsonophagocytic activity geometric mean titers, geometric mean fold rises, and post-booster IgG concentrations stratified by pre-vaccination status before the primary dose. These outcome descriptions identify what was intended to be assessed; numerical immunogenicity results are not reported in the registry record.

The record does not report a sample-size justification, detailed allocation procedure, or statistical analysis plan. The enrollment figure describes how many participants entered the study, not how many contributed data to every endpoint.

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: Overall, a total of 151 participants were assigned and vaccinated with a single booster dose of group B streptococcus 6-valent polysaccharide conjugate vaccine (GBS6) (20 microgram \[μg\] capsular polysaccharide \[CPS\]/serotype/dose) formulated with or without aluminum phosphate (AlPO4) based on the formulation received in the primary C1091001 study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All the participants reporting "yes" or "no" for at least 1 day were included in the analysis.

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: Safety population included all participants who received 1 booster dose and had at least 1 safety assessment after receiving the booster dose.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Reporting Prompted Local Reactions Within 14 Days Following Booster Dose (Redness, Swelling, and Pain at the Injection Site), measured over Within 14 days after booster dose.

The primary endpoint is the percentage of participants reporting a prompted local reaction within 14 days after the booster dose. The reactions are pain, redness, and swelling at the injection site. Local symptoms are commonly recorded as safety outcomes because they describe events participants experience soon after vaccination and can be assessed using prespecified categories of severity.

Participants recorded local reactions using an electronic diary. Pain was graded from mild, meaning it did not interfere with activity, to moderate, severe, or grade 4. Moderate pain included repeated use of a nonnarcotic pain reliever for more than 24 hours or interference with activity. Severe pain included any use of a narcotic pain reliever or prevention of daily activity. Grade 4 meant an emergency room visit or hospitalization.

Redness and swelling were graded by size: mild was 2.0-5.0 centimeters, moderate was greater than 5.0-10.0 centimeters, and severe was greater than 10.0 centimeters. Grade 4 redness meant necrosis or exfoliative dermatitis; grade 4 swelling meant necrosis. The maximum severity for each reaction location within the 14-day period was derived, so the recorded grade reflects the highest grade reported during that period.

The endpoint’s analysis population includes participants who reported yes or no for at least 1 day. This definition does not establish that every participant completed all diary days. The number of participants with endpoint data, the percentages by group, and the associated confidence intervals are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are converted into summaries and how much uncertainty accompanies those summaries. The registry describes a percentage endpoint and lists a 95% confidence interval as its dispersion measure. It does not report the method used to calculate that interval, any group-comparison method, or a complete statistical analysis plan. The concepts below are general explanations of how such methods are commonly interpreted, not claims about unreported procedures in this trial.

What does a percentage endpoint describe?

A percentage of participants with an event is a binary outcome summary: each participant is classified as having reported the event or not having reported it under the endpoint definition. For this endpoint, the event is at least one prompted local reaction in the 14-day period. The percentage depends on both the number of participants classified as having a reaction and the number contributing endpoint data. The registry specifies that participants reporting yes or no for at least 1 day were included, but the actual endpoint denominators and event counts are not reported in the registry record.

That analysis-population definition matters. A participant with diary information for only part of the observation period may be eligible for inclusion under the stated rule, while a participant with no yes-or-no report for any day would not meet that rule. The record does not report how many participants had incomplete diaries, how missing days were handled, or whether sensitivity analyses were performed. Therefore, the stated rule should not be mistaken for evidence that all participants had complete observations.

What does a confidence interval communicate?

A 95% confidence interval is an uncertainty summary around an estimate. In general, repeated use of a method with suitable assumptions would yield intervals that cover the target value at the stated long-run rate. A confidence interval is not a guarantee that a particular interval contains the true value, and it is not a statement that there is a 95% probability the result is correct. Its practical interpretation depends on the interval method and the data structure.

For a percentage, precision is influenced by the number of participants with endpoint data and the observed frequency. Smaller denominators generally lead to less precise estimates than larger denominators, though the precise interval width also depends on the estimate and the calculation method. The registry names a 95% confidence interval for the primary outcome but does not report the estimate or interval. Its precision therefore cannot be judged from the record.

Why distinguish description from comparison?

Group-specific counts and percentages describe what was observed in each group. A comparison asks whether the observed difference is compatible with chance variation under a specified model and, where relevant, whether the groups can support a causal interpretation. Non-randomized assignment can leave groups different in ways that affect outcomes. Even a formal statistical test cannot by itself remove confounding created by assignment or make non-comparable groups equivalent.

The registry identifies non-randomized allocation and states that the arms are not a like-for-like control comparison. The group safety figures should therefore be read descriptively. The record does not report an adjusted comparison, a hypothesis test, or a method for accounting for potential baseline differences. No comparative effect estimate or p-value for the primary endpoint is reported.

What is the role of severity grading?

Severity categories make symptom reports more interpretable than an undifferentiated yes-or-no record alone. In this trial, pain grading incorporates interference with activity, medication use, or emergency care. Redness and swelling grading uses measured size and specifies severe tissue outcomes for grade 4. Taking the maximum severity by reaction location over the observation period summarizes the highest recorded grade, rather than the duration or cumulative burden of symptoms.

These grading rules define how a reported event is categorized; they do not provide the actual distribution of grades. The registry record does not report counts by severity grade, nor does it report the local-reaction percentages. It is therefore not possible to distinguish the frequency of mild reports from more severe reports using the available results.

How should planning calculations be read?

Planning sample-size calculations are design illustrations, not observed results. The described planning approach uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Such assumptions describe a hypothetical calculation and do not establish that the trial used those assumptions to choose its enrollment. The registry does not report its own sample-size justification.

Calculations based on an observed effect are sensitive to the effect estimate chosen, especially when that estimate is uncertain. A planning illustration does not show that a completed study had a particular probability of detecting an effect. It is not observed power, and it does not replace examination of the estimate and confidence interval. No numerical planning outputs or observed primary effect are reported in the registry record, so no calculation result can be interpreted from the information available.

For event-count outcomes in general, methods may differ from those for continuous outcomes such as geometric mean concentrations. The registry lists immunogenicity summaries based on geometric means and fold rises, but does not describe transformations, modeling choices, handling of values below assay limits, or inferential procedures. Those details are not reported in the registry record and should not be inferred from the outcome names alone.

10. Multiplicity, Missing Data and Analysis Populations

The study lists several secondary immunogenicity outcomes across serotypes and measurement types. Examining multiple outcomes can create a multiplicity issue: when many statistical tests are conducted, the chance of at least one apparently unusual result can increase if each test is interpreted independently. General approaches include prespecifying a hierarchy of outcomes, adjusting significance thresholds, or treating results as exploratory. The registry record does not report whether any such approach was planned or used.

The registry describes 10 outcome measures and 0 analyses. It does not report a complete analysis plan, planned hypothesis-testing hierarchy, adjustment for multiple comparisons, or outcome-specific statistical results. The number and variety of listed outcomes alone do not reveal how they were prioritized or interpreted.

Missing-data handling is also not reported. For the primary local-reaction analysis, the stated population includes participants who reported yes or no for at least 1 day. The record does not say how partial diary completion was handled beyond that criterion, how many records were incomplete, or whether missingness differed between groups. For immunogenicity outcomes, the registry does not report the number of participants with measurements at each time point or how missing measurements were handled.

The enrolled population and an endpoint analysis population need not be identical. Enrollment of 151 does not establish that 151 participants contributed to every outcome. The available safety denominators are 76 and 75 for each group, but these denominators should not automatically be treated as the analysis populations for the primary endpoint or immunogenicity outcomes.

Analysis populations such as all enrolled participants, participants who received vaccination, or participants with evaluable measurements can answer different questions. The registry does not report a full set of population definitions or endpoint-specific denominators. These omissions limit assessment of whether exclusions or missing measurements could have influenced the reported summaries.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thermal burn (1.3%).

The safety summary lists serious adverse events for 76 participants in the GBS6 20 μg with AlPO4 group and 75 in the GBS6 20 μg without AlPO4 group. Serious events affected 1 participant in the group with AlPO4 and 0 in the group without AlPO4. Other adverse events affected 59 and 54 participants, respectively. The registry reports 0 deaths in each group.

The registry lists Thermal burn, 1.3%, among the top serious terms. That entry identifies a term and a percentage in the serious-event summary; it does not, on its own, establish that the event was caused by the vaccine. The available record does not provide additional detail about the event or a causal assessment.

These figures are counts from the listed groups, not a randomized comparison. The study was non-randomized, and the registry cautions that the arms are not like-for-like controls. Differences in counts cannot therefore be treated as evidence that one formulation caused more or fewer events than the other. The record also does not report the full event narratives or all details needed to interpret exposure time and event attribution.

Zero deaths means none were recorded in the listed groups in this summary; it does not establish that an event is impossible or that all potential safety concerns have been excluded.

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

The trial record describes a booster study in adults previously given a primary GBS6 dose, and it defines how local reactions were to be recorded and graded. It also provides selected safety counts. These elements help readers understand the questions asked and the information captured, but they are not a substitute for the endpoint results.

The primary question concerns the percentage of participants reporting local reactions within 14 days. The registry record does not report that percentage, its confidence interval, or the group-specific event counts. It is therefore not possible to quantify the primary endpoint or its precision from the record. The listed immunogenicity outcomes likewise lack numerical results, so no conclusion about changes in IgG concentrations, opsonophagocytic activity, or fold rises can be drawn from the outcome descriptions alone.

The safety counts show that serious adverse events were reported for 1 participant in the group with AlPO4 and 0 in the group without AlPO4, while other adverse events were reported for 59 and 54 participants. Those counts are descriptive, and the non-randomized design does not support treating the groups as equivalent apart from the formulation difference. The serious-event term listing does not establish causality.

In general, interpreting a clinical trial requires attention to both the estimated effect and its uncertainty, the population analyzed, missing observations, and the design used to form comparisons. Here, the record does not report primary effect estimates, confidence intervals, or a detailed analysis plan. It also does not report its own sample-size justification or missing-data procedures.

The study’s stated aim was to evaluate safety and immunogenicity and to determine whether participants had additional benefit following a booster. That is an objective, not a finding. The available registry information supports description of the design and selected safety summaries, but not a conclusion that the booster did or did not produce a particular clinical or immunological effect.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how endpoint definitions and study design shape interpretation. The primary outcome is a participant-level percentage, but its meaning depends on the observation window, diary completion rule, and severity definitions. The registry specifies these features, including the 14-day window and the use of maximum severity by reaction location. That makes the intended measure more explicit, even though the numerical result is not reported.

The non-randomized allocation is central to interpreting the two groups. When assignment is not random, group differences can reflect factors other than the intervention contrast. The registry itself cautions against treating the arms as like-for-like controls. This means descriptive summaries should not be mistaken for causal estimates, and statistical adjustment cannot be assumed because it is not reported in the record.

The study also includes multiple immunogenicity measures: concentrations, functional titers, fold rises, and a stratified post-booster concentration outcome. These measures address different statistical summaries and questions. Their presence illustrates why outcome definition and multiplicity planning matter. However, without numerical results or an analysis plan, readers cannot judge the size, precision, or evidential strength of an immunogenicity finding.

Finally, the record distinguishes enrollment from endpoint-specific information by giving safety denominators while leaving primary and immunogenicity results unreported. This is a useful reminder that an enrolled total does not automatically define the denominator for every outcome. Clear reporting of estimates, intervals, analysis populations, and missing-data handling is necessary for a complete 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 main limitation for interpreting efficacy-related or immunogenicity findings is that the registry does not report numerical results for the primary local-reaction endpoint or the listed secondary immunogenicity outcomes. No event percentages, confidence intervals, antibody summaries, fold rises, or group comparisons are available in the record. As a result, neither effect size nor precision can be assessed for those outcomes.

Design also limits comparative interpretation. The study was open-label and non-randomized, and the registry specifically warns that its groups are not a like-for-like control comparison. The record does not report the assignment basis or a method to address potential differences between groups. Accordingly, the group-level safety counts are descriptive rather than evidence of a causal formulation contrast.

For the local-reaction endpoint, participants needed to report yes or no for at least 1 day to be included. The record does not report the number excluded under this rule, diary completeness, or the handling of missing days. It also does not provide severity-specific results, although severity grading is described.

The registry record does not report a statistical analysis plan, multiplicity strategy, sample-size justification, or detailed analysis populations. It lists multiple immunogenicity outcomes but provides no numerical analyses. These omissions make it difficult to assess planned versus reported analyses, endpoint prioritization, or the impact of missing observations.

The available safety summary is limited to listed event counts, deaths, and a top serious term. It does not provide enough detail to assess all event characteristics or determine causality. These limitations are specific to the information recorded and should not be filled by assumptions about procedures or results that are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF A GROUP B STREPTOCOCCUS 6 VALENT POLYSACCHARIDE CONJUGATE VACCINE (GBS6) IN HEALTHY ADULTS — NCT04258995.
• Registry record last updated 2021-10-13; status last verified 2021-10.
• Results first posted 2021-10-13.
• 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

NCT04258995 is a completed Phase 2, open-label, non-randomized, parallel-group study of a GBS6 booster in healthy adults who had previously received a primary dose. The registry lists enrollment of 151 and two groups receiving GBS6 20 μg with or without AlPO4. The primary endpoint is the percentage reporting prompted local reactions within 14 days. Listed secondary outcomes concern serotype-specific IgG and opsonophagocytic activity measures.

Safety summaries report 1 serious adverse event among 76 participants in the group with AlPO4 and 0 among 75 in the group without AlPO4; other adverse events affected 59 and 54 participants, respectively. No deaths are reported. The registry does not report numerical results for the primary or immunogenicity outcomes, or a detailed statistical analysis plan. Because allocation was non-randomized, the groups are not a like-for-like control comparison.