This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Immunogenicity and Safety of GSK Biologicals' Infanrix/Hib in Children (NCT00696423), a non-randomized phase 3 study. The primary outcome is Anti-polyribosyl-ribitol-phosphate (PRP) Antibody Concentrations.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00696423 |
| Phase | Phase 3 |
| Condition | Acellular Pertussis, Diphtheria, Tetanus |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 467 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Chinese children aged 18 to 24 months receiving a booster dose. The primary immunogenicity analysis is described as using the According To Protocol cohort for immunogenicity. The registry record does not report further eligibility details for that cohort.
Intervention
One dose of Infanrix mixed with Hiberix before administration as a single injection. The record describes this as the Infanrix/Hib Single Injection Group.
Comparator
Infanrix and Hiberix administered as separate injections, described as the Infanrix + Hiberix Separate Injection Group. Allocation was non-randomized, so the groups are not a like-for-like control comparison.
Primary question
What anti-polyribosyl-ribitol-phosphate (PRP) antibody concentrations were observed one month after booster vaccination in the immunogenicity analysis cohort, and how precisely were those concentrations estimated? The registry record identifies geometric mean concentration and a 95% confidence interval, but does not report their numerical values.
The study concerns both immunogenicity and safety. The primary outcome focuses on anti-PRP antibody concentrations; secondary outcomes include concentrations or seroprotection and seropositivity measures for other listed antibodies, as well as reported symptoms and adverse events. The central comparison is the administration format: a mixed single injection versus separate injections of the two products. Because assignment was non-randomized, observed differences between groups cannot automatically be attributed to the administration format. The registry record does not report the allocation process, baseline group characteristics, or the numerical primary outcome results, so it does not support a quantitative estimate of how the groups compared.
3. Trial Design
The registry record describes a completed, parallel-group Phase 3 study sponsored by GlaxoSmithKline. Its brief summary calls the booster-phase study Phase IIIB. The study compares GSK Biologicals' DTPa/Hib vaccine with separately administered DTPa and Hib vaccines in Chinese children aged 18 to 24 months, with safety and immunogenicity as the stated areas of assessment. The record identifies 467 enrolled participants. That enrollment figure should not be treated as the number analyzed for the primary outcome: the primary analysis population is described separately as the According To Protocol cohort for immunogenicity, and its size is not reported in the registry record.
One group received a dose of Infanrix mixed with Hiberix and administered in one injection. The other received Infanrix and Hiberix as separate injections. The record classifies allocation as non-randomized, masking as none, and the model as parallel. It also explicitly cautions that the arms are not a like-for-like control comparison. In practical terms, the record does not establish that group assignment was independent of participant characteristics or other factors that could be related to antibody concentrations or safety reporting. The absence of masking also means that participants and study personnel were not described as masked to the assigned administration approach.
The primary endpoint is measured one month after booster vaccination. The record lists secondary antibody outcomes involving PRP, diphtheria toxoid, tetanus toxoid, pertussis antigens, and seroprotection or seropositivity classifications. It also lists symptom reporting, unsolicited adverse events, and serious adverse events. The record gives no numerical primary endpoint result, and it does not report the numerical results for these secondary outcomes as a set. The protocol posting is described as covering the booster phase; the primary phase objectives and outcome measures are identified as belonging to a separate protocol posting, NCT00412854. The registry record does not report a detailed statistical plan or a 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.
Overall Study
| Stage | Infanrix/Hib Single Injection Group | Infanrix + Hiberix Separate Injection Group |
|---|---|---|
| STARTED | 244 | 223 |
| COMPLETED | 244 | 218 |
| NOT COMPLETED | 0 | 5 |
Reasons for not completing this period:
| Reason | Infanrix/Hib Single Injection Group | Infanrix + Hiberix Separate Injection Group |
|---|---|---|
| Lost to Follow-up | 0 | 5 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the According To Protocol (ATP) cohort for immunogenicity.
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.
| Characteristic | Unit | Infanrix/Hib Single Injection Group | Infanrix + Hiberix Separate Injection Group | Total |
|---|---|---|---|---|
| Participants analysed | 244 | 223 | 467 | |
| Age, Continuous | months | 19.2 (SD 0.79) | 19.2 (SD 0.75) | 19.2 (SD 0.77) |
| Sex: Female, Male: Female | Participants | 113 | 111 | 224 |
| Sex: Female, Male: Male | Participants | 131 | 112 | 243 |
6. Primary Endpoint
The registry lists the primary outcome as Anti-polyribosyl-ribitol-phosphate (PRP) Antibody Concentrations, measured over One month after booster vaccination.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | μg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is anti-polyribosyl-ribitol-phosphate (PRP) antibody concentration, measured in μg/mL one month after booster vaccination. PRP is the antibody target named in the registry record. The endpoint is summarized as a geometric mean concentration, with a 95% confidence interval, in the According To Protocol cohort for immunogenicity.
A geometric mean is a way of summarizing positive measurements when the distribution is better described by multiplicative variation than by additive variation. In general, it is calculated by taking the mean on a logarithmic scale and converting that mean back to the original measurement scale. This summary can be useful for antibody concentrations, which may vary over a wide range and often have a right-skewed distribution. The registry record specifies the geometric mean but does not report the individual concentration data or the numerical geometric mean values.
A confidence interval describes uncertainty around an estimated quantity. In general, a 95% confidence interval gives a range of values compatible with the data under the method used to construct it; it is not a guarantee that a particular interval contains the underlying quantity. Here, the interval is specified for the geometric mean concentration, but neither its endpoints nor the underlying estimates are reported in the registry record. Therefore, the endpoint definition alone does not show the magnitude or precision of the observed antibody concentrations, and it does not establish a numerical difference between the groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a primary immunogenicity outcome and its analysis population, but does not report the numerical primary outcome estimates. It specifies geometric mean anti-PRP antibody concentrations in μg/mL, assessed one month after booster vaccination, together with a 95% confidence interval. The actual geometric means, interval limits, and any numerical comparison between the administration groups are not reported in the registry record. As a result, the primary result cannot be described in terms of its direction, size, or precision from this record.
The allocation is non-randomized, and the record cautions that the arms are not a like-for-like control comparison. That design feature matters even if numerical group estimates were available. A difference in observed antibody concentrations could reflect the administration approach, but it could also reflect differences between children assigned to the groups, differences in care or measurement, or other factors. The record does not report enough information about allocation or baseline group characteristics to evaluate those possibilities. No causal interpretation is warranted from the registry description alone.
The registry lists 467 enrolled participants, while the primary analysis is identified as the According To Protocol cohort for immunogenicity. The size and characteristics of that cohort are not reported in the registry record. Enrollment and analysis populations need not be identical: an analysis cohort can depend on protocol adherence and availability of measurements. Without the cohort size, reasons for exclusion, or missing-data information, it is not possible to judge how the analysis set relates to the enrolled group.
The registry also lists safety outcomes. Its adverse-event entries report 133 affected in the Infanrix/Hib Single Injection Group, with 244 at risk, and 127 affected in the Infanrix + Hiberix Separate Injection Group, with 223 at risk. The serious-event affected entries are 1 and 3, respectively; the serious-event at-risk entries and deaths are not reported in the registry record. Bronchopneumonia is listed among the top serious terms at 0.9%, and bronchitis at 0.4%. These entries do not by themselves provide a complete safety comparison: the record does not explain the relevant event definitions, analysis details, or the basis for those percentages. It also does not report numerical results for the primary immunogenicity endpoint, so the safety entries cannot fill that gap.
The record lists 13 outcome measures, but its structured analysis count is 0. This indicates that numerical statistical analyses are not available in the registry record; it does not establish what analyses were conducted outside the posted record. Without outcome estimates, uncertainty intervals, and analysis details, the record supports describing the study question and design but not drawing a statistical conclusion about a group difference.
9. Statistical Methods Explained
The primary outcome is a geometric mean concentration, and the stated uncertainty measure is a 95% confidence interval. The registry record does not include the numerical estimate or interval endpoints. The methods below explain how these statistical terms are generally interpreted; they do not assert unreported analysis procedures for this study.
What does a geometric mean describe?
In general, the geometric mean is appropriate when values are positive and relative, rather than absolute, differences are meaningful. It is calculated by transforming values to a logarithmic scale, averaging on that scale, and transforming the average back. This makes the geometric mean less dominated by a few very large values than an arithmetic mean can be when measurements are right-skewed. Antibody concentrations are often analyzed with this kind of summary, but the registry record only confirms that a geometric mean was reported as the planned summary measure; it does not give the underlying values or describe any transformation details.
The geometric mean remains a summary of a distribution. It does not show how spread out the individual measurements are, whether there are unusual values, or whether every participant has a concentration near the summary. The confidence interval gives information about uncertainty in the estimated mean, not the full range of participant-level values. A reader would need the estimate, interval, and additional distributional information to assess the observed concentrations in detail.
How should a confidence interval be read?
In general, a confidence interval expresses the precision of an estimate under a statistical method and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale, while an interval that spans a broad range leaves more uncertainty about the underlying value. A 95% confidence interval is a method-based coverage statement over repeated applications of the method; it is not the probability that the fixed underlying quantity lies within the particular reported interval. In this study record, the 95% confidence interval is specified, but its limits are not reported, so the precision cannot be evaluated.
If a study reports separate confidence intervals for group estimates, those intervals alone are not always a direct test of the difference between groups. A contrast should be estimated and accompanied by its own uncertainty measure using an appropriate method. The registry record does not report a numerical contrast, a confidence interval for a contrast, or a hypothesis test for the primary outcome. It therefore does not support a claim about statistical compatibility or incompatibility between the group estimates.
Why does non-random allocation matter?
In general, random allocation aims to make assignment independent of participant characteristics, on average. Non-random allocation can leave differences between groups in measured or unmeasured characteristics. Such differences can influence an outcome and complicate interpretation of a group comparison. The registry record classifies allocation as non-randomized and specifically warns that the arms are not a like-for-like control comparison. It does not report the allocation mechanism or enough baseline information to assess the extent of any imbalance. Statistical adjustment can address measured characteristics under suitable assumptions, but it cannot automatically remove bias from unmeasured factors; the record does not report an adjusted analysis.
Masking is listed as none. In general, knowledge of the assigned intervention can affect behavior, reporting, clinical attention, or outcome assessment, especially for outcomes involving reported symptoms. Antibody concentration is a laboratory measurement, but the record does not describe laboratory masking or measurement procedures. It would therefore be inappropriate to assume that every potential source of information bias was absent or controlled.
What is over-dispersion, and is it relevant?
In general, over-dispersion occurs when observed variability in count or binary outcomes is greater than a statistical model assumes. It can make standard errors too small if a model treats the data as less variable than they are. This issue may matter for analyses of adverse-event counts or symptom reporting, depending on how the data are structured and modeled. The registry record does not report model specifications or enough event-level detail to determine whether over-dispersion was assessed. It is a general consideration, not a finding about this study.
What do the planning illustrations mean?
The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These illustrations are not the trial's own design justification and are not observed power. Because the primary numerical result and the illustration values are not reported in the registry record, no sample-size value or effect magnitude can be interpreted. In general, a planning calculation is conditional on its assumed effect and statistical model; it does not establish that a completed study had a particular probability of detecting an effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 13 outcome measures, covering antibody concentrations, seroprotection or seropositivity classifications, and safety reporting. When a study assesses several outcomes, or makes several comparisons, the chance of at least one apparently unusual result can increase if each is interpreted independently. In general, multiplicity procedures can control that risk, but they involve choices about which outcomes form a family and how the error rate is handled. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or a statistical analysis plan, so it is not possible to determine how the outcomes were intended to be interpreted together.
The record's structured analysis count is 0. This means that the registry record does not contain analysis entries to evaluate; it does not establish that investigators performed no analyses. Numerical primary and secondary outcome results, hypothesis tests, and confidence intervals beyond the primary endpoint's stated format are not reported in the registry record. The record also does not state whether analyses were adjusted for baseline values or other covariates.
For missing data, the record identifies the According To Protocol cohort for immunogenicity but does not describe how that cohort was defined, how many participants were included, or how missing antibody measurements were handled. It does not report reasons for missing measurements or whether any sensitivity analyses were performed. These details matter because restricting an analysis to participants with protocol-compliant data can affect how well the analyzed group represents those enrolled. The registry record also does not report a sample-size justification. Its planning illustrations are described as post hoc illustrations based on the observed effect, not as evidence of the original design assumptions.
11. What the Result Does, and Does Not, Mean
The registry record establishes the question being studied: anti-PRP antibody concentration one month after a booster, comparing a mixed Infanrix/Hib injection with separately administered Infanrix and Hiberix. It specifies a geometric mean and 95% confidence interval for the primary endpoint and identifies the immunogenicity analysis cohort. It does not report the numerical primary estimates, the interval limits, or a direct estimate of the group contrast. Consequently, the record does not show the direction, size, or precision of any primary outcome difference.
Even if group estimates were available, the non-randomized allocation and the warning that the arms are not a like-for-like comparison would limit causal interpretation. In general, an observed difference is not automatically an effect of the intervention when group assignment may be associated with participant characteristics or other factors. The registry record does not provide enough allocation or baseline information to assess those potential differences, and it does not report an adjusted comparison.
The safety entries describe affected counts and at-risk counts for the groups, as well as serious-event affected entries and selected serious-event terms. They do not substitute for the unreported immunogenicity result. Nor do the entries alone establish a comprehensive safety comparison: the registry record does not report definitions, a detailed analysis population, or a full numerical account of the listed safety outcomes. Deaths and serious-event at-risk entries are not reported in the registry record.
In general, a registry record is useful for identifying the study design, outcomes, and reported results, but an outcome definition is not itself an outcome finding. The available record supports a descriptive account of the trial and its planned primary measure. It does not establish that either administration approach produces higher antibody concentrations, that the approaches are equivalent, or that either has a particular safety profile. Those conclusions would require numerical results and adequate information about analysis methods, data completeness, and potential group differences.
12. Why This Trial Matters Statistically
This study is statistically notable because it compares administration approaches in a non-randomized design. The registry record explicitly states that the arms are not a like-for-like control comparison. That caution is central to interpretation: numerical differences, if reported, would need to be considered alongside the possibility that the groups differed for reasons other than the injection approach. A clear distinction between an observed association and a causal effect is essential in clinical research.
The primary outcome also illustrates why both an estimate and its uncertainty matter. A geometric mean summarizes antibody concentrations, while a confidence interval communicates precision in that estimate. The registry record names these measures but does not include their numerical values. Without those values, readers cannot judge the magnitude or precision of the primary outcome, and cannot evaluate a numerical comparison between the groups.
The study also lists a broad range of immunogenicity and safety outcomes. Multiple outcomes can provide a wider descriptive picture, but they raise questions about multiplicity, outcome prioritization, and how findings should be interpreted together. The registry record does not report a statistical plan or multiplicity approach. Its description of planning illustrations further underlines the distinction between planning calculations and observed evidence: the illustrations are not the original design justification and are not observed power.
Finally, the primary analysis population is described as an According To Protocol cohort, distinct in definition from the enrolled population, but its size and handling of missing measurements are not reported. That gap limits assessment of how representative the analyzed participants are. Together, these features make transparent reporting of estimates, uncertainty, analysis populations, and design limitations especially important for interpreting this trial.
13. 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 the posted results is that numerical primary outcome estimates are not reported in the registry record. Although the endpoint, measurement unit, timing, summary measure, and confidence-interval format are specified, the geometric mean concentrations and interval limits are absent. A numerical comparison between the groups is also not reported. The primary immunogenicity finding therefore cannot be assessed for magnitude or precision.
Non-randomized allocation and the registry's own warning that the arms are not a like-for-like comparison limit interpretation of any between-group difference. The record does not describe how participants were assigned, report baseline characteristics, or give an adjusted comparison. It also lists no masking. The record does not describe laboratory procedures or whether outcome assessors were masked, so the potential influence of knowledge of group assignment cannot be evaluated in detail.
The primary analysis uses the According To Protocol cohort for immunogenicity, but its size and definition are not reported. The record does not explain missing measurements, exclusions, protocol deviations, or sensitivity analyses. It also does not provide a statistical analysis plan, multiplicity approach, or sample-size justification. These omissions make it difficult to assess the robustness and completeness of the analysis from the registry record alone.
Safety reporting is also limited in detail. The record includes affected and at-risk entries, selected serious-event terms, and no reported death count, but does not provide a full account of event definitions or analysis procedures. The study is described as addressing a booster phase, while primary-phase objectives and outcome measures are assigned to a separate protocol posting. Its conclusions should therefore be understood only in relation to the booster-phase question and the information recorded for this trial.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Immunogenicity and Safety of GSK Biologicals' Infanrix/Hib in Children — NCT00696423.
- Registry record last updated 2018-06-06; status last verified 2016-10.
- Results first posted 2009-08-26.
- 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.
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17. Record Summary
The registry record describes a completed, parallel, non-randomized Phase 3 study sponsored by GlaxoSmithKline; its brief summary refers to the study as Phase IIIB. It lists 467 enrolled participants and compares one mixed Infanrix/Hib injection with separate Infanrix and Hiberix injections in Chinese children aged 18 to 24 months.
The primary outcome is geometric mean anti-PRP antibody concentration in μg/mL one month after booster vaccination, with a 95% confidence interval, in the According To Protocol cohort for immunogenicity. The numerical primary outcome result is not reported in the registry record. The record lists 13 outcome measures and 0 structured analysis entries. It cautions that allocation was non-randomized and the groups are not a like-for-like control comparison. Details of the immunogenicity cohort, missing data, multiplicity procedures, and statistical analysis plan are not reported in the registry record.