Immunogenicity and Safety of Boostrix Polio Vaccine as a Booster Dose in 5 to 6-year-old Children.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of Boostrix Polio Vaccine as a Booster Dose in 5 to 6-year-old Children. (NCT00871000), a randomized phase 3 study. The primary outcome is Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations.

2. Clinical Question

3. Trial Design

This completed phase 3 study, described in its summary as phase 3b, was designed to compare immunogenicity and reactogenicity after booster vaccination with Boostrix Polio or Tetravac in healthy children aged 5 to 6 years. The registry lists randomized allocation, no masking, and a parallel-group model. The sponsor was GlaxoSmithKline.

Children in both groups had previously received three doses of a DTPa-based vaccine according to the Italian 3-5-11 month schedule. The arm descriptions specify prior Infanrix vaccination. The Boostrix Polio group received a single booster dose of Boostrix Polio; the Tetravac group received a single booster dose of Tetravac. MMRV vaccine was co-administered to all children according to the study summary. Consequently, the intended comparison is between two booster vaccine regimens in the context of co-administration, not a comparison of co-administration against no co-administration.

The registry records enrollment of 303. It gives a study start date of 2009-04-01 and a primary completion date of 2009-11-18, and lists the study status as completed. These design details describe the planned and recorded study structure; they do not establish that every enrolled participant contributed data to every outcome. The analysis population for the primary immunogenicity outcome is described separately as an according-to-protocol cohort.

Although allocation was randomized, masking is listed as none. The registry record does not describe the allocation sequence or concealment procedures, or provide further detail about how the unmasked design was implemented. The interpretation of outcome estimates should therefore remain tied to the information recorded, without assuming procedures not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects who had received the booster dose of study/comparator vaccine and for whom immunogenicity data and assay results for antibodies against at least one study vaccine antigen component 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 Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations, measured over At Month 1, one month post-vaccination.

The primary outcome is anti-diphtheria and anti-tetanus antibody concentration measured at Month 1, one month post-vaccination. Concentrations are expressed in IU/mL and summarized as geometric mean concentrations, with 95% confidence intervals. The registry also gives a reference cut-off of at least 0.1 IU/mL.

Antibody concentration provides a quantitative measure of the immune response recorded after vaccination. A geometric mean is a summary suited to measurements that are analyzed on a multiplicative scale: it reflects the central level after accounting for the distribution of values on a logarithmic scale, then expressing the summary in the original units. This is a general description of the statistic, not a claim about the unreported calculation details of this trial.

The cut-off supplies a reference for interpreting whether a concentration meets the registry’s stated threshold. It is conceptually distinct from the group geometric mean: a group average does not show how many individual participants were above or below the cut-off. The registry lists seroprotection outcomes among the secondary outcomes, while the primary endpoint is concentration.

The registry record does not report the group GMC estimates or their confidence intervals for this primary endpoint. Thus the endpoint definition is available, but the recorded primary outcome information does not support a numerical description of the observed antibody concentrations or their comparative precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean summarize?

A geometric mean is a way to describe the central level of measurements when values are naturally interpreted multiplicatively or have a skewed distribution. In general, the values are transformed to a logarithmic scale, averaged on that scale, and transformed back. The result remains in the original measurement units, IU/mL in this trial. It is not the same statistic as an arithmetic mean, and it does not describe the spread of individual measurements by itself.

The registry identifies geometric mean concentrations as the primary summary, but it does not report the specific computational details used to derive them. Nor does the record give the actual GMCs. The explanation of the statistic is therefore general; it should not be mistaken for a reconstruction of the trial’s analysis.

How should a 95% confidence interval be read?

A confidence interval conveys uncertainty around an estimated quantity. In general, an interval that is narrower indicates greater precision for that estimate under the analysis assumptions, while a wider interval indicates more uncertainty. A 95% confidence interval is not a statement that 95% of individual antibody measurements lie within its limits. It concerns the estimated group summary, not the range of participant-level values.

The registry states that primary GMCs were reported with 95% confidence intervals, but it does not provide their limits. As a result, neither the precision of the group summaries nor the precision of a contrast can be evaluated from the primary outcome information in the record.

What does the antibody cut-off mean?

The record gives a reference cut-off of at least 0.1 IU/mL. A cut-off can be used to classify measurements according to a stated criterion, and the registry lists seroprotection outcomes as secondary outcomes. A continuous concentration summary and a threshold-based count answer different questions: the former describes a group’s concentration level, while the latter concerns how many participants satisfy the criterion. Neither can be derived from the other without participant-level information or the relevant reported results.

The threshold’s presence does not establish that a participant above it is protected in every clinical circumstance. The registry gives the cut-off as a reference value for the outcome; broader clinical meaning is not established by that definition alone.

What can be inferred from the design?

Random allocation is intended, in general, to make treatment groups comparable on average with respect to factors that could affect outcomes. A parallel-group design assigns participants to a group and compares outcomes across groups. Masking is listed as none, so the record does not describe a masked trial. The registry does not report further details on the allocation process or how outcome assessment was conducted.

Randomization does not guarantee that groups are identical in every respect, and it does not replace examination of the observed outcomes. In this record, the primary estimates needed for that examination are not reported. The analysis population is described as an according-to-protocol immunogenicity cohort, rather than as all enrolled participants. This distinction means the population used for the primary analysis may differ from the enrollment total, but the record details do not give the cohort size or explain exclusions in detail.

What do the planning assumptions represent?

The registry’s sample-size assumptions describe a planning illustration computed from the observed effect, using 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. These assumptions characterize an illustration for planning, not the original trial’s design justification. The record does not report the trial’s own sample-size justification or the resulting planning counts in the registry record for this account.

Such planning counts are not observed power. Observed power is not a substitute for reading the estimated effect and its uncertainty, and a post hoc planning calculation does not establish that a trial was adequately planned. Here, without the primary GMC estimates, the observed effect used in the illustration cannot be independently interpreted from the registry’s primary outcome entry.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means that variation is greater than a simple model would expect. If a model assumes too little variability, uncertainty can be understated and statistical conclusions can be misleading. This is a general modeling consideration, not a method reported for this trial. The registry entries do not specify a count model or indicate that over-dispersion was assessed.

What analysis details are not recorded?

The registry outcome description identifies the measure, summary statistic, confidence interval, timing, and analysis cohort in partial terms. It does not report a full statistical analysis plan, the specific model or test for the primary comparison, adjustment variables, handling of multiple comparisons, interim analyses, or detailed missing-data procedures. Those methods should not be inferred from the use of GMCs or confidence intervals. The evidence available supports describing the stated endpoint and design, while leaving those analytic decisions unreported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary antibody-concentration outcome and multiple secondary outcomes, covering diphtheria, tetanus, pertussis, and MMRV-related antibody measures. Testing or estimating several outcomes can raise multiplicity concerns: when many comparisons are considered, the chance of at least one apparently notable result may increase. This is a general statistical issue, not evidence that a particular error occurred in this study.

The registry record does not report whether the analyses used a multiplicity adjustment, which outcomes were included in any formal testing hierarchy, or whether the secondary outcomes were intended to be descriptive. It also does not report an interim analysis plan. No multiplicity strategy should therefore be attributed to the trial on the basis of the outcome list alone.

The primary analysis population is described as an according-to-protocol cohort for immunogenicity, consisting of evaluable participants who received the booster and had immunogenicity and assay results for at least one study vaccine antigen. The description in the registry record does not give the cohort size or the full criteria for evaluability. It does not explain how missing measurements, withdrawals, protocol deviations, or assay failures were handled, or whether additional analysis populations were used.

These omissions limit assessment of how participant inclusion may affect the estimates and how consistently outcomes were available across groups. They do not establish that missing data or multiplicity changed the results; the relevant procedures and numerical results are not reported in the registry record. The enrollment figure should not be treated as the denominator for every endpoint without outcome-specific information.

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 zero participants affected by serious events among the 151 participants at risk in the Boostrix Polio group, and zero among the 152 at risk in the Tetravac group. It also lists zero deaths in each group. For other events, the registry lists 117 affected among 151 at risk in the Boostrix Polio group and 117 among 152 at risk in the Tetravac group.

These are recorded counts, not estimates of comparative risk or proof of equivalence. A zero serious-event count means no affected participants were recorded in these entries; it does not establish that the underlying risk is zero. The registry lists no top serious event terms, so the record does not identify serious-event types in this summary. The other-event counts do not convey the specific events, their severity, duration, timing, or relationship to vaccination. Nor should the counts be interpreted as showing that the event experience would be the same outside this study population.

The study summary says reactogenicity was assessed, but these safety entries alone do not provide a detailed account of reactogenicity outcomes. The registry record does not report further safety results in the registry record.

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

The central statistical point is that the registry describes the primary endpoint but does not report its numerical results. It identifies anti-diphtheria and anti-tetanus geometric mean antibody concentrations at Month 1, with 95% confidence intervals, in an according-to-protocol immunogenicity cohort. That information is enough to understand what the planned primary measure represents, but not enough to compare the observed group concentrations.

Accordingly, no conclusion about the direction, size, or precision of the primary comparison can be drawn from the recorded endpoint information. The registry does not establish that the groups had the same concentrations, that one group had higher concentrations, or that a difference met any statistical criterion. The stated cut-off of at least 0.1 IU/mL does not supply missing group results or tell how many individuals met the criterion.

The study design and enrollment describe the context in which outcomes were assessed. They do not answer whether a result is clinically important, whether it generalizes to other populations, or whether the booster regimens differ in safety. The safety entries report zero serious-event cases and zero deaths in each group, with 117 participants affected by other events in each group; they do not give event-level detail or prove that serious harms are impossible.

The registry lists secondary immunogenicity outcomes, but their numerical results are not included in the record details for this analysis. The primary endpoint therefore cannot be supplemented with conclusions about those outcomes. A reader can distinguish the stated question from the observed evidence: the question and design are documented, while the numerical primary comparison is not reported in the registry record. Any stronger claim about efficacy, immunogenicity superiority, equivalence, or overall safety would require results and analysis details that are not reported.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why endpoint definitions and endpoint results must be kept separate. The registry identifies a quantitative primary measure, its units, summary statistic, confidence interval, timing, and analysis cohort description. Those details make the intended question understandable. Yet without the actual GMC estimates and confidence intervals, the primary comparison cannot be evaluated. A clearly specified outcome is not a substitute for a reported estimate.

The distinction between a continuous concentration outcome and a threshold-based outcome is also important. The primary endpoint summarizes concentrations, while the record lists seroprotection counts among secondary outcomes. These outcomes address related but distinct features of the immune response. A group average alone cannot reveal the distribution of participant values or the number crossing the stated reference cut-off.

The design supplies context for interpreting a future or separately reported estimate: randomized allocation, parallel groups, no masking, and co-administration of MMRV to all children. These features shape what the comparison represents. In particular, because both groups received MMRV, the recorded comparison concerns the two booster regimens under co-administration, not the effect of adding MMRV.

The record also illustrates why enrollment, safety counts, and outcome estimates should not be conflated. Enrollment describes study size at the registry level; the primary analysis is described as an according-to-protocol cohort; and the safety entries use their own listed risk denominators. None of these quantities supplies the missing primary concentration results. Statistically careful reading preserves these distinctions rather than drawing a conclusion from the study objective or design alone.

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 consequential limitation for interpretation is that the registry record does not report the primary GMC estimates or confidence-interval limits. This prevents assessment of the observed anti-diphtheria and anti-tetanus concentrations, the group contrast, and its precision. Numerical results for the listed secondary immunogenicity outcomes are also not included in the registry record.

The analysis population description is incomplete for evaluating participant flow. It identifies an according-to-protocol immunogenicity cohort and gives a general eligibility description, but does not report the cohort size, detailed exclusions, or missing-data handling. The enrollment figure cannot stand in for endpoint-specific denominators.

The registry lists no masking. It does not provide further details about allocation concealment, outcome assessment, or analytic safeguards. It also does not report a full statistical analysis plan, multiplicity approach, interim analyses, or the trial’s own sample-size justification. These items should be treated as unreported rather than assumed to have followed a particular procedure.

The safety information is limited to group counts for serious events, other events, and deaths. No top serious event terms are listed, and event descriptions, timing, severity, and attribution are not given in the registry record. The counts therefore offer only a narrow view of safety reporting.

Finally, the study concerns healthy children aged 5 to 6 years with a specified prior vaccination history and a particular co-administration context. The registry record alone does not establish how findings would apply to populations or schedules outside that description. Since the primary numerical results are not reported, even conclusions limited to this study population cannot be made about the comparative antibody response.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of Boostrix Polio Vaccine as a Booster Dose in 5 to 6-year-old Children. — NCT00871000.
• Registry record last updated 2018-06-06; status last verified 2017-04.
• Results first posted 2017-04-18.
• 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

NCT00871000 is a completed randomized, parallel-group phase 3 study, described in the study summary as phase 3b, sponsored by GlaxoSmithKline. It enrolled 303 healthy children aged 5 to 6 years who had received three primary doses of a DTPa-based vaccine according to the Italian 3-5-11 month schedule. The groups received a single booster dose of Boostrix Polio or Tetravac, with MMRV co-administered to all children. Masking is listed as none.

The primary outcome was anti-diphtheria and anti-tetanus antibody concentration at Month 1, reported as GMCs in IU/mL with 95% confidence intervals and a reference cut-off of at least 0.1 IU/mL. The registry record does not report the primary GMC estimates or their confidence intervals. Safety entries list zero serious-event cases and zero deaths in each group, and 117 participants affected by other events in each group. Detailed safety findings and several analysis procedures are not reported in the registry record.