Immunogenicity and Safety Study of Booster Dose of GSK Biologicals' IPV (Poliorix™) and DTPa/Hib (Infanrix+Hib™) Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of Booster Dose of GSK Biologicals' IPV (Poliorix™) and DTPa/Hib (Infanrix+Hib™) Vaccine (NCT01449812), a randomized phase 3 study. The primary outcome is Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Toxoids.

2. Clinical Question

The study concerns healthy Chinese toddlers who had completed a primary vaccination course and were between 18 and 24 months of age at booster vaccination. Its central statistical questions were whether antibodies against diphtheria and tetanus remained above the study’s seroprotection threshold before the booster, and how immune responses and safety were characterized after booster vaccination.

This is a persistence question at Day 0, not a reported estimate of the change in antibody levels after vaccination. The study also included post-booster immune-response and safety objectives, but the registry record does not report comparative immune-response estimates. Therefore, the available information describes the question and study structure more fully than it describes the primary outcome findings.

3. Trial Design

This was a randomized, phase 3, parallel-group study with no masking. The registry lists 831 participants as enrolled and the study status as completed. The start date is 2011-10-01, and the primary completion date is 2012-01-16. GlaxoSmithKline is listed as the sponsor.

The study focused on healthy Chinese toddlers previously enrolled in a primary vaccination study. The registry describes two groups primed with three doses of Infanrix-IPV/Hib™ on different schedules: at 2, 3 and 4 months of age, or at 3, 4 and 5 months of age. A control group had been primed with Infanrix+Hib™ and Poliorix™ at 2, 3 and 4 months of age. At booster vaccination, children were between, and including, 18 and 24 months of age.

The study description says that the booster phase evaluated immune persistence and assessed safety and immune response to booster vaccination. The arm descriptions in the registry record are truncated, so the full description of what each group received in the booster phase is not reported in the registry record. Allocation details, including the randomization procedure and allocation ratio, are not reported in the registry record.

The primary endpoint was a count of subjects seroprotected against diphtheria and tetanus before booster vaccination, at Day 0. Its analysis population was the According-to-Protocol cohort for antibody persistence, defined by completion of the full primary course and availability of serological results at the persistence time. The record lists 29 outcome measures, including solicited local and general symptoms, unsolicited adverse events, and serious adverse events. It does not report inferential analyses for these outcomes.

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 analysis of antibody persistence, which included all subjects who have completed their full three-dose primary vaccination course in the DTPA-IPV-056 study and for whom serological results were available at the persistence time point.

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 Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Toxoids, measured over Before the booster vaccination (At Day 0).

The primary endpoint is the number of subjects seroprotected against diphtheria and tetanus toxoids before booster vaccination, at Day 0. A subject met the registry’s seroprotection definition when anti-D and anti-T antibody concentrations were each at least 0.1 IU/mL. The measure is a participant count, rather than a mean antibody concentration or a change from baseline.

Seroprotection thresholds classify antibody measurements using a prespecified concentration boundary. In general, such a measure is used to describe how many people in an analysis population meet that criterion at a particular assessment. It can summarize persistence of antibody levels following earlier vaccination, which is the role of this endpoint in the study: the assessment occurred before the booster, after participants had completed their primary vaccination course.

The endpoint alone does not describe the full distribution of antibody concentrations, how close measurements were to the threshold, or how responses changed after booster vaccination. Nor does the endpoint definition by itself establish a comparison between groups. The registry identifies the ATP cohort for antibody persistence as the analysis population, but does not report the seroprotected counts, the denominators analyzed, or group-specific estimates. Thus, the endpoint’s meaning and threshold are described, but its observed result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design and the statistical evidence answer different questions. Randomization assigns participants to groups according to a chance-based procedure, which can support fair comparisons when the allocation process is implemented and analyzed appropriately. The registry identifies the study as randomized, but the specific procedure, allocation ratio, and concealment details are not reported in the registry record. The parallel-group structure means participants were assigned to a group rather than described as crossing through each group’s intervention.

What does the primary measure represent?

The endpoint is a count of participants meeting a binary seroprotection definition. For each subject, antibody concentrations against diphtheria and tetanus are classified against the threshold of at least 0.1 IU/mL. In general, binary outcomes simplify individual measurements into categories, such as meeting or not meeting a criterion. The resulting count depends on both the threshold and the participants included in the analysis. It does not show the range of antibody concentrations within either category.

The timing is important for interpretation. The primary assessment is specified as before booster vaccination, at Day 0, and concerns persistence after primary vaccination. It is not a reported post-booster change measure. The registry describes a separate booster-phase interest in immune response, but the primary endpoint stated in the record is the pre-booster seroprotection count.

Why does the analysis population matter?

The stated population is the According-to-Protocol cohort for antibody persistence. It includes subjects who completed their full three-dose primary vaccination course and had serological results available at the persistence time. In general, a protocol-defined population can differ from everyone enrolled or randomized because eligibility for analysis may depend on adherence, completion, or available measurements. The registry record does not give the final analysis denominator, the number of missing serology results, or reasons for exclusion. Those omissions prevent assessment of how selection into this cohort may have affected the result.

What can the safety counts show?

Safety outcomes are reported as participant counts. The serious adverse event figures indicate how many participants in each group were recorded as having such an event among those at risk. A count is descriptive: it states what was recorded in the group, without by itself showing whether an observed difference is compatible with chance or whether groups were comparable on other factors. General statistical comparisons would require a defined contrast and an analysis method. Neither a comparative estimate nor its precision is reported for these figures.

The top serious-event terms, febrile convulsion and bronchopneumonia, are each listed with a frequency of 0.4%. The registry does not provide the distribution of these terms by group in the posted summary. Event terms should also be distinguished from participant counts: a person can have more than one event, and a term-level summary is not necessarily equivalent to a count of unique participants unless the reporting definition says so. Further detail about event coding and counting is not reported in the registry record.

What is absent from the statistical report?

The registry lists 29 outcome measures and zero analyses. It does not report a statistical analysis plan, a model for the primary endpoint, hypothesis tests, confidence intervals, or missing-data procedures. It also does not report whether any interim analyses were conducted or how multiplicity was handled. These details cannot be inferred from the randomized design or from the endpoint name.

In general, multiplicity arises when many outcomes or comparisons are examined: the chance of at least one apparently notable finding can increase as the number of tests grows. Methods for addressing it depend on the planned objectives and analysis strategy. Since neither the testing strategy nor analysis results are reported, it is not possible to assess whether multiplicity adjustments were used or to interpret any comparative significance.

In general, over-dispersion is relevant for some count-data models when observed variability exceeds what a model assumes. This endpoint, however, is defined as a count of participants meeting a binary criterion, and the registry does not state a model or describe over-dispersion. There is no basis in the record for attributing a particular count model or variance assumption to the analysis.

The posted record supplies no numerical primary endpoint result from which to assess effect size or precision. There are also no recalculated estimates reported. Any sample-size planning illustration based on an observed effect would be distinct from the trial’s observed evidence and would not represent observed power. The registry does not report the trial’s own sample-size justification or design assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, including immune-response and safety outcomes, but reports zero analyses. It does not state how many hypotheses were tested, which comparisons were prespecified, or whether a multiplicity adjustment was planned or used. In general, testing multiple outcomes or comparisons can increase the chance of obtaining at least one apparently notable result by chance. The appropriate way to address that issue depends on the prespecified testing strategy; that strategy is not reported in the registry record.

The primary endpoint analysis was defined for the According-to-Protocol cohort for antibody persistence. Eligible subjects had completed the full three-dose primary course and had serological results available at the persistence time. The record does not state how many participants met these criteria, how missing measurements were handled, or whether any alternative analysis populations were used. It does not describe imputation, sensitivity analyses, or reasons that participants may have been excluded.

Since the primary endpoint counts and analysis denominators are absent, the impact of missing data cannot be evaluated. In general, missingness can affect interpretation if participants without a result differ systematically from those with a result. Whether that occurred in this study is not reported in the registry record.

The statistical analysis plan, including test selection, model specification, handling of protocol deviations, and interim analyses, is not reported in the registry record. The absence of these details means the analysis methods and the control of false-positive findings cannot be assessed from the posted 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile convulsion (0.4%), bronchopneumonia (0.4%).

The serious adverse event summary records 1 participant with a serious adverse event among 272 at risk in the Infanrix+Hib/Poliorix 1 Group. It records 0 among 273 at risk in the Infanrix+Hib/Poliorix 2 Group and 0 among 280 at risk in the Control Group. Deaths are recorded as 0 in each group. These are descriptive group counts, not estimates of comparative risk or evidence of a statistically established difference.

The registry lists febrile convulsion and bronchopneumonia as top serious adverse event terms, each reported at 0.4%. It does not indicate the group assignment of these terms in the posted summary. The terms therefore should not be attributed to a particular group based on these figures alone.

In general, a serious adverse event is a safety classification and is not interchangeable with any adverse event or a solicited symptom. The registry separately lists solicited local symptoms, solicited general symptoms, unsolicited adverse events, and serious adverse events as outcomes. The record also reports other affected-participant counts of 157 among 272, 164 among 273, and 158 among 280, but does not provide enough detail in the summary to characterize those counts beyond the listed other-event category.

No comparative statistical analysis, uncertainty interval, event narratives, or causal assessment is reported in the registry record. The counts describe what was recorded; they do not by themselves establish whether an event was caused by vaccination or how groups compare.

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

The registry record establishes that this randomized phase 3 study was designed to examine antibody persistence before booster vaccination and to evaluate immune response and safety in healthy Chinese toddlers with different primary vaccination histories. It defines seroprotection against diphtheria and tetanus using an antibody threshold of at least 0.1 IU/mL and specifies an ATP cohort for the persistence analysis.

What the record does not establish is the primary result. It does not report the number of subjects who met the seroprotection definition, the corresponding group denominators, or comparative estimates. The record also does not report post-booster immune-response estimates. Consequently, it is not possible to assess the magnitude, direction, or precision of the immune outcomes from the registry record.

The reported serious adverse event counts are low in the descriptive sense that the summary lists 1 participant in one group and 0 in each of the other groups. Those counts are not a statistical comparison. The record does not include uncertainty intervals or an analysis of whether group differences could reflect chance. It also does not provide enough event-level detail to assess the circumstances of the listed serious-event terms.

In general, a trial’s design and outcome definitions explain what investigators intended to evaluate; they are not substitutes for outcome results. Randomization alone does not disclose the observed treatment-group estimates, and a count alone does not establish a causal effect. Interpretation would require the group-specific endpoint data, analysis denominators, analysis methods, and precision estimates, none of which are reported for the primary outcome in this record.

The study therefore supports a description of its population, design, endpoint definition, and posted safety counts. It does not support a conclusion about comparative immune response, the degree of antibody persistence, or a treatment effect. It also does not permit a complete assessment of missing data, multiplicity, or the robustness of the analyses.

13. Why This Trial Matters Statistically

This study illustrates why endpoint timing and definition are central to clinical-trial interpretation. Its primary endpoint is a threshold-based count measured before booster vaccination, at Day 0. That makes it a measure of antibody persistence after primary vaccination, rather than a direct estimate of the response produced by the booster. The registry’s separate interest in post-booster immune response should not be conflated with the primary endpoint.

The study also highlights the importance of describing the analysis population. The antibody-persistence endpoint was defined for subjects who completed the full primary course and had serological results available at the persistence time. Without the analysis denominator and the number of eligible participants, the reader cannot establish how much of the enrolled population contributes to the primary analysis or assess the possible effect of unavailable measurements.

Randomized groups with different prior vaccination schedules may be informative for comparisons, but valid interpretation depends on knowing the planned contrasts and seeing the estimated outcomes with their precision. The registry record names the groups but does not report primary endpoint estimates or comparative analyses. The safety counts are likewise descriptive, rather than a substitute for a prespecified comparison.

Finally, the record lists many outcomes but no analyses. This makes the distinction between outcomes of interest and reported evidence especially important. In general, when several outcomes or comparisons are considered, the analysis plan helps readers understand which results were primary and how multiplicity was addressed. Those methods are not reported. The study’s record is therefore useful for understanding the design and measurement framework, but incomplete for evaluating the statistical evidence on its main immune endpoint.

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 trial-specific limitation of the registry record is that the primary endpoint results are not reported. The endpoint is defined as a count of seroprotected subjects before booster vaccination, but group-specific counts and analysis denominators are absent. The record also does not report comparative immune-response estimates after booster vaccination.

The analysis population is described as an According-to-Protocol cohort for antibody persistence, limited to subjects who completed the full primary series and had serological results available. The record does not give the cohort size, the number with missing serology, reasons for missing data, or exclusions. This prevents assessment of whether the analyzed cohort differed from the enrolled population.

The arm descriptions are truncated, leaving the full booster regimen for each group unclear in the registry record. The randomization procedure, allocation ratio, and masking details beyond the listing of no masking are not elaborated. The statistical analysis plan, sample-size justification, interim analyses, and multiplicity strategy are also not reported in the registry record.

Safety information is limited to group counts and top serious-event terms. The registry does not report event narratives, group-specific frequencies for each listed term, comparative estimates, or uncertainty intervals. The figures should therefore be read as descriptive records rather than as a complete statistical safety analysis.

These limitations concern what is available in the registry record; they do not establish that additional study documentation or analyses do not exist elsewhere. The posted information alone is insufficient to evaluate the precision or robustness of the primary endpoint findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of Booster Dose of GSK Biologicals' IPV (Poliorix™) and DTPa/Hib (Infanrix+Hib™) Vaccine — NCT01449812.
• Registry record last updated 2018-06-06; status last verified 2017-04.
• Results first posted 2017-04-13.
• 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

NCT01449812 is a completed randomized, unmasked, parallel-group phase 3 study sponsored by GlaxoSmithKline, with 831 participants listed as enrolled. It studied healthy Chinese toddlers aged 18 to 24 months at booster vaccination who had previously completed primary vaccination schedules involving Infanrix-IPV/Hib™ or Infanrix+Hib™ and Poliorix™.

The primary endpoint was the number of subjects seroprotected against diphtheria and tetanus before booster vaccination, at Day 0, using a threshold of at least 0.1 IU/mL for anti-D and anti-T antibody concentrations. The registry record does not report the primary endpoint counts or comparative immune-response analyses.

Serious adverse events are recorded for 1 participant among 272 at risk in the Infanrix+Hib/Poliorix 1 Group, 0 among 273 in the Infanrix+Hib/Poliorix 2 Group, and 0 among 280 in the Control Group. Deaths are recorded as 0 in each group. Statistical methods, missing-data handling, and multiplicity procedures are not reported in the registry record.