Safety and Immunogenicity of a Booster Dose of GSK Biological's Boostrix-Polio Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of a Booster Dose of GSK Biological's Boostrix-Polio Vaccine (NCT00635128), a non-randomized phase 4 study. The primary outcome is Number of Subjects With Any Grade 3 Solicited Local Symptoms.

2. Clinical Question

3. Trial Design

This completed Phase 4 study evaluated a booster dose of Boostrix-Polio in children and adolescents. The registry lists an enrollment of 415, a parallel-group model, non-randomized allocation and no masking. The study start date was 2008-02-01, and primary completion was 2008-07-08. These design details describe how the trial was recorded; they do not establish that the groups were comparable at baseline.

Participants were aged 9 to 13 years and had taken part in the dTpa-IPV-001 (711866/001) study 5 years earlier. The two group labels refer to the earlier vaccination: Boostrix-Polio Group and Boostrix + IPV Mérieux Group. In the current study, both groups received a single booster dose of Boostrix-Polio. Consequently, the comparison is between groups with different prior vaccination histories, rather than between current booster and no booster.

The registry describes evaluation of immune persistence as well as immunogenicity, safety and reactogenicity after vaccination. It lists outcomes covering solicited symptoms, antibody concentrations or status for diphtheria, tetanus and pertussis antigens, and polio protection or antibody titers. The listed primary outcome is a count of participants with any Grade 3 solicited local symptom during the specified follow-up period.

Because assignment was non-randomized and both groups received the booster, observed differences between the groups would not, by themselves, isolate a causal effect of the current booster or establish what would have happened without it. The registry record does not report the allocation procedure, a masking procedure, or a randomized control group. It also does not report a statistical analysis plan or sample-size justification.

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: During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Any Grade 3 Solicited Local Symptoms, measured over During the 4-day (Days 0-3) follow-up period after booster vaccination.

The primary endpoint counts participants who experienced any Grade 3 solicited local symptom during the 4-day (Days 0-3) follow-up period after booster vaccination. The solicited local symptoms were pain, redness and swelling at the injection site. Each symptom has a defined severity threshold in the registry: Grade 3 pain prevented normal activity, while Grade 3 redness or swelling spread beyond 50 millimeters from the injection site.

This is a binary participant-level outcome: a participant either met the definition for at least one of the specified Grade 3 local symptoms during the follow-up period or did not. The endpoint is reported as a number of participants, not as the total number of symptom episodes. A participant with more than one qualifying symptom would still count once for this endpoint.

Soliciting symptoms means the study specifically assessed the listed reactions rather than relying only on spontaneous reports. A severe-symptom threshold focuses the endpoint on reactions meeting the registry's Grade 3 definitions. Such a count can describe how often the defined outcome was recorded in the assessed participants. It does not, on its own, characterize every local symptom, its duration, or the broader safety profile.

The registry record states the endpoint definition and analysis population but does not report the primary endpoint result. Therefore, the number meeting this definition, and the precision of that estimate, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count of participants meeting a yes-or-no definition. For each participant in the analysis population, the relevant question is whether any solicited local symptom met the Grade 3 definition during the stated follow-up period. In a binary outcome analysis, the event count is interpreted alongside the number of participants whose outcome data were included. This makes the denominator important: a count without its analysis population does not show how completely the outcome was assessed.

The registry says that the primary analysis used the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available. This wording identifies the intended population for that endpoint, but it does not describe how many participants had missing symptom information, how missing observations were handled, or whether any other analysis population was used for secondary outcomes. Those details are not reported in the registry record.

For a participant-level binary endpoint, a group estimate is often expressed as the proportion with the event, accompanied by a confidence interval. A confidence interval describes the uncertainty around an estimate under the assumptions of the analysis; it is not a guarantee that the true value lies within the interval. When event counts are small or absent, ordinary approximations can be unreliable, and methods suited to sparse binary data may be considered. The registry record does not report an estimate, confidence interval, statistical test or method for the primary endpoint, so no such analysis can be evaluated from the recorded results.

A contrast between groups could be expressed using a difference in proportions or another measure of relative or absolute association. Each measure answers a different question, and each requires the actual event counts and denominators. No new contrast can be derived from the registry information without the primary outcome counts. More fundamentally, this trial's non-randomized allocation means any group contrast would remain vulnerable to differences associated with the groups' earlier vaccination histories. Statistical adjustment, if used, might address measured differences but would not automatically remove unmeasured confounding. Whether adjustment was planned or performed is not reported in the registry record.

The registry lists 12 outcome measures, covering solicited symptoms and several immune-response measures. When many outcomes are examined, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for multiplicity. Multiplicity procedures can control or otherwise describe this issue, but the choice depends on the analysis plan and the purpose of the comparisons. The registry record does not report a multiplicity strategy or outcome-specific analyses. It reports no analyses, so there are no listed p-values to interpret as confirmatory or exploratory.

The registry also describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations are hypothetical planning tools: they illustrate the number of participants per arm under selected assumptions, rather than report an outcome of the trial. They are not observed power. The record does not report the trial's own sample-size justification, and no planning count should be treated as evidence that the study was designed to detect a particular clinically meaningful effect.

In general, power is the probability that a specified statistical procedure will detect an effect of a chosen size under stated assumptions. A planning calculation depends on the assumed effect, outcome variability, significance threshold, allocation and analysis method. If the assumed effect comes from observed data, the illustration inherits the uncertainty of that estimate. A smaller effect to detect generally requires more information for the same target power, all else equal; this is a general statistical relationship, not a result reported for this trial. The posted calculations should be read as planning illustrations under their stated assumptions, not as a retrospective measure of whether the trial succeeded.

Counts of adverse events require similarly careful interpretation. Serious-event counts and other adverse-event counts are distinct categories, and the denominator at risk indicates the group considered for those figures. Zero observed serious events does not imply zero possible risk. Estimating how precisely a low event frequency has been characterized would require an appropriate interval and clarity about event ascertainment and follow-up. Those details are not reported beyond the endpoint's stated follow-up period and the listed safety counts.

The study's design also shapes what methods can establish. Randomization is a method for balancing, on average, measured and unmeasured baseline factors across groups; it was not used. Masking can reduce some forms of measurement or reporting bias; the registry lists no masking. These design features do not make recorded counts meaningless, but they limit the strength of causal comparisons. The registry record does not report additional procedures that might address these limitations.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures spanning safety, reactogenicity and immunogenicity, but reports no analyses. It does not state how the primary endpoint was prioritized relative to secondary outcomes for statistical testing, whether any adjustment for multiple comparisons was planned, or whether the listed outcomes were intended to be descriptive or confirmatory. A multiplicity strategy is not reported in the registry record. Without results and a stated testing approach, there is no basis for judging a family of p-values or identifying a statistically supported secondary finding.

For the primary endpoint, the Total Vaccinated Cohort included all vaccinated subjects for whom data were available. This defines the population described for that analysis, but the record does not say how missing symptom records were handled, whether participants with incomplete follow-up were excluded, or how missingness was assessed. Methods for missing data in the secondary outcomes are also not reported in the registry record. Missingness can affect both the denominator and the interpretation of an outcome, particularly if availability of measurements is related to symptoms or participant characteristics.

The registry does not report whether outcomes were analyzed by assigned group, by actual vaccination, or using another population definition beyond the stated primary analysis population. It does not give analysis-specific denominators for the primary endpoint or immunogenicity outcomes. The safety figures do list participants at risk for the adverse-event categories, but they do not fill in the absent primary endpoint results. These gaps limit assessment of completeness, selective analysis and the robustness of any comparison.

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 non-serious adverse event terms

The registry lists serious adverse events as 0 among 351 participants at risk in the Boostrix-Polio Group and 0 among 64 participants at risk in the Boostrix + IPV Mérieux Group. Deaths are listed as 0 in each group, and no top serious-event terms are listed. These are recorded counts, not proof that serious events cannot occur. With zero observed events, the underlying risk remains uncertain; an uncertainty interval and fuller event-ascertainment details would be needed for a more complete assessment.

The registry separately records other adverse events affecting 281 of 351 participants in the Boostrix-Polio Group and 51 of 64 participants in the Boostrix + IPV Mérieux Group. These figures should not be confused with the primary outcome, which counts participants with Grade 3 solicited local symptoms during the 4-day (Days 0-3) follow-up period. The record does not provide a breakdown of these other events by type, severity or timing.

Because the study was non-randomized and both groups received the booster, the listed counts are descriptive. The groups also reflect different earlier vaccination histories. These safety figures alone cannot establish a causal difference between the groups or characterize all possible adverse events.

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

The registry record establishes the study question and design: children and adolescents who had participated in an earlier study received a Boostrix-Polio booster, and the study was intended to assess immune persistence, immunogenicity, safety and reactogenicity. It specifies a primary endpoint focused on participants with any Grade 3 solicited local symptom during a 4-day (Days 0-3) period. That definition makes clear what the endpoint was intended to count.

However, the primary endpoint result is not reported in the registry record. The record therefore does not show how many participants met the Grade 3 local-symptom definition, how precisely the outcome was estimated, or whether the groups differed on that endpoint. The registry lists other adverse-event counts, including zero serious adverse events in the groups, but these are not substitutes for the missing primary outcome result.

The study also lists antibody and seroprotection outcomes, but their results are not reported. No conclusion about persistence of immunity, response to the booster, or protection can be drawn from outcome titles alone. Likewise, an outcome being listed does not show that it was analyzed or that a particular result was obtained.

The non-randomized design matters for interpretation. Both groups received the current booster, while their earlier vaccination histories differed. A comparison between them cannot directly estimate what would have happened without the booster, and group differences would not necessarily be attributable to the current vaccination. The record does not report analyses that could clarify or adjust for such differences.

Accordingly, the posted information supports a description of the trial's stated purpose, endpoint, design and recorded safety counts. It does not establish the frequency of the primary outcome, a treatment effect, a comparative immune response, or the absence of risk. Those questions require outcome results and methods that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and outcome results need to be read separately. The primary endpoint is specified in detail: it counts participants with at least one qualifying Grade 3 local symptom during a defined follow-up period. Yet the registry record does not report the corresponding count. A precise definition helps explain what a result would mean, but it cannot replace the result itself.

The study also shows how prior treatment history can shape a comparison. The two groups were formed around different vaccinations in an earlier study, and both received Boostrix-Polio in the present study. Because allocation was non-randomized, a contrast between groups would not have the same interpretation as a randomized comparison. This is especially relevant when a reader might otherwise interpret the group labels as intervention and control.

Safety reporting further demonstrates the distinction between event categories. The registry records no serious adverse events in either group, while other adverse events are recorded in both. The primary endpoint is a separate, narrowly defined solicited local symptom outcome. Keeping these categories distinct prevents one count from being mistaken for another and avoids treating a zero serious-event count as proof of no risk.

Finally, the listed immune outcomes and the absence of reported analyses set limits on statistical interpretation. The number of outcomes makes multiplicity a relevant consideration, but no analysis or multiplicity approach is recorded. The trial can therefore be understood from its design and outcome definitions, while conclusions about efficacy, immunogenicity and the primary safety endpoint remain unsupported by the registry results.

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 most important limitation for interpreting outcomes is that the primary endpoint result is not reported in the registry record. Without the event count, denominator for that endpoint, or an uncertainty estimate, its frequency and precision cannot be assessed. The record lists 12 outcome measures but reports no analyses, leaving the listed immune and symptom outcomes without reported results.

Allocation was non-randomized and masking was absent. The two groups differed in earlier vaccination history, while both received the same current booster. This design does not provide a randomized no-booster comparison and cannot by itself separate the effect of the current booster from other group differences. The registry record does not report baseline comparisons, adjustment methods or other analytic approaches that might help evaluate confounding.

The primary analysis population is described as the Total Vaccinated Cohort, including vaccinated subjects for whom data were available. However, the registry record does not report the number with primary outcome data, the extent or pattern of missing observations, or the method used to handle missingness. It also does not state whether the same population definition applied to all secondary outcomes.

The safety figures give serious and other adverse-event counts, but the record does not provide detailed terms for serious events, uncertainty intervals, or a full breakdown of other adverse events. Zero recorded serious events should not be read as evidence that the risk is zero. Finally, the registry record does not report a sample-size justification, statistical analysis plan or multiplicity procedure. These omissions prevent a full assessment of planned comparisons, precision and selective outcome reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of a Booster Dose of GSK Biological's Boostrix-Polio Vaccine — NCT00635128.
• Registry record last updated 2018-06-06; status last verified 2017-04.
• Results first posted 2017-07-05.
• 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

NCT00635128 is a completed Phase 4, non-randomized, unmasked, parallel-group study sponsored by GlaxoSmithKline. It evaluated a single Boostrix-Polio booster in healthy male or female subjects aged 9 to 13 years who had participated in the dTpa-IPV-001 study 5 years earlier. Both groups received the current booster, with group labels reflecting earlier vaccination history. Enrollment was 415; the study started on 2008-02-01 and primary completion was 2008-07-08.

The primary endpoint was the number of participants with any Grade 3 solicited local symptom during the 4-day (Days 0-3) follow-up period. Primary endpoint results and analyses are not reported in the registry record. The safety figures list 0 serious adverse events and 0 deaths in each group, alongside other adverse events affecting 281 of 351 and 51 of 64 participants, respectively. The registry lists 12 outcome measures but no analyses, limiting conclusions about the primary outcome, immunogenicity and comparisons between groups.