Immune Memory of DTPw-HBV/Hib Vaccine Following Primary Vaccination, Immuno & Reacto of a Booster Dose Given in Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immune Memory of DTPw-HBV/Hib Vaccine Following Primary Vaccination, Immuno & Reacto of a Booster Dose Given in Infants (NCT00169442), a randomized phase 3 study. The primary outcome is Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL.

2. Clinical Question

3. Trial Design

This was a randomized, Phase 3, parallel-group trial with no masking recorded. The registry lists enrollment as 745 and status as completed. The study began on 2005-02-10, with primary completion on 2006-03-01. GlaxoSmithKline is listed as the sponsor.

The trial’s stated purpose was to assess immune memory after primary vaccination with DTPw-HBV/Hib and to assess the immunogenicity and reactogenicity of a booster given at 15-18 months of age. The official title also describes a plain PRP polysaccharide dose at 10 months for some groups and booster options at 15-18 months. The arm descriptions include infants primed with combined vaccine, infants primed with DTPw-HBV and Hiberix, and groups receiving plain PRP before a later booster.

Several intervention and arm names appear in the record, but it does not give a complete, unambiguous account of every arm’s assigned treatment sequence. Some arm descriptions end before specifying the full booster regimen. The registry record does not report the allocation ratio or a detailed randomization procedure. Although allocation is recorded as randomized, no masking is listed.

The primary endpoint was a count of participants meeting each of two anti-PRP antibody thresholds, measured at Month 1 after the PRP challenge. The analysis population was the ATP cohort for immunogenicity. The record lists 29 outcome measures, but does not report an analysis for the primary endpoint. Thus the design and endpoint can be described, but the posted results do not permit an estimate of the primary response or a comparison among groups.

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

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 for whom data concerning immunogenicity measures 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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL, measured over At Month 1, post-PRP challenge.

The primary endpoint counts participants whose anti-PRP antibody concentrations reached or exceeded two stated thresholds: 0.15 μg/mL and 1.0 μg/mL. Measurement was specified at Month 1 after the PRP challenge. The registry describes the endpoint as the number of subjects meeting each threshold, rather than as a mean antibody concentration or a change from baseline.

Threshold endpoints are used to describe how many participants meet a defined antibody level. Reporting more than one threshold can characterize responses at different levels, but each threshold count remains a separate outcome. A count alone does not indicate the proportion of the analysis population unless the corresponding denominator is also reported. Counts also do not show how close measurements were to a threshold or how antibody concentrations were distributed among participants.

The stated analysis population comprised evaluable participants with available immunogenicity data in the According-to-Protocol cohort. The registry record does not include the observed endpoint counts, denominators by group, uncertainty intervals, or a reported comparison. Consequently, the endpoint’s definition is clear, but its results and precision cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group design and records no masking. Random allocation is intended, in general, to make assigned groups comparable with respect to both measured and unmeasured characteristics on average. It does not ensure that every group will be identical, and it does not remove the need to examine who was included in each analysis. The registry record does not describe the randomization sequence, allocation concealment, or the allocation ratio. No masking is recorded; further operational details about who knew assignments are not reported in the registry record.

What does the endpoint count?

The primary endpoint is a count of participants whose anti-PRP antibody concentration met each of two thresholds at Month 1 after the PRP challenge. The measure is therefore categorical at each threshold: a participant either meets that threshold or does not. The two thresholds should be read as separate criteria, not combined into one total. Counts need denominators to convey how common threshold attainment was within a group. The registry record does not report the endpoint counts or the relevant group denominators.

What does the analysis population mean?

The primary population is the According-to-Protocol cohort for immunogenicity. The record defines it as evaluable subjects with available immunogenicity data. In general, an according-to-protocol analysis can exclude participants who do not meet specified protocol or evaluability conditions. The rules used to determine eligibility for this cohort, the number excluded, and the reasons for exclusion are not reported in the registry record. Because the outcome is based on available data in an evaluable cohort, its interpretation may differ from an analysis including everyone assigned at random.

How should a group comparison be interpreted?

For a threshold outcome, a statistical comparison would ordinarily relate the number meeting the threshold to the number assessed in each group. An estimate of a difference or another effect measure could then describe how the groups compare, with an uncertainty interval to show precision. General statistical explanation: a small observed difference can be compatible with a range of underlying effects when the data are imprecise, while a more precise estimate narrows that range. The registry record does not report a chosen effect measure, a comparison, a confidence interval, or a p-value for the primary endpoint. It also does not identify a single primary group contrast.

What is known about multiplicity?

The record lists 29 outcome measures, including multiple antibody endpoints and thresholds. When many outcomes or comparisons are tested, the chance of at least one apparently notable finding can increase. General methods for addressing this include defining a primary comparison in advance or adjusting interpretation for multiple testing. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any adjustments were made. The count of outcome measures alone does not establish how many statistical tests were conducted.

What can the sample-size assumptions tell us?

The record describes planning illustrations based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are described as illustrations, not as the trial’s own design justification. The registry record does not report a sample-size justification, the target effect used for the original design, or a primary analysis result from which to assess an observed effect. Such planning calculations are not observed power and do not show whether the trial’s result was precise.

What statistical details remain unavailable?

The registry record does not report the primary analysis method, a model specification, confidence intervals, p-values, handling of missing observations, or interim analyses. It also does not report whether analyses were adjusted for baseline characteristics or other factors. These omissions limit reproducibility and prevent a detailed evaluation of the statistical assumptions. General statistical explanation: model choice should correspond to the type of outcome and study design, and uncertainty should reflect the analysis population and any clustering or other data structure when relevant. The registry record does not indicate that such additional structures were used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 29 outcome measures, including the primary anti-PRP threshold counts and secondary antibody outcomes for PRP, diphtheria, tetanus, hepatitis B, and pertussis-related measures. A broad outcome set can raise multiplicity concerns if many comparisons are tested. General statistical explanation: when many hypotheses are examined, some results may appear unusual by chance alone, even if there is no underlying difference. Prespecifying a primary comparison, defining an outcome hierarchy, or using an adjustment are possible approaches, but the registry record does not report whether any of these were used.

The primary analysis population is the According-to-Protocol cohort for immunogenicity, defined as evaluable participants with immunogenicity data available. The record does not state the number of participants included in that analysis by group, the criteria for evaluability, the extent or pattern of missing measurements, or the method used to handle missing data. It is therefore not possible to compare the primary analysis population with all randomized participants or to assess how exclusions may have affected the results.

The record lists zero analyses. It does not report a statistical analysis plan, interim analyses, a primary comparison, or adjustments for multiplicity. These details are not reported in the registry record. As a result, neither the treatment of missing data nor the control of false-positive findings across the listed outcomes can 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: bronchopneumonia (1.2%).

The registry lists serious adverse event figures for a PRP Pooled Group, a Mix Pooled Group, and a Tritanrix-HepB Kft.+Hiberix Group. The serious-event counts are 1 among 85 at risk in the PRP Pooled Group, 0 among 410 at risk in the Mix Pooled Group, and 0 among 250 at risk in the Tritanrix-HepB Kft.+Hiberix Group. The record lists 0 deaths in each of these groups.

Two additional PRP groups are listed with 0 serious adverse events among 42 and 43 at risk, respectively, and 0 deaths in each. These figures should be read as recorded counts for the named groups, not as evidence of a causal relationship or as proof that events cannot occur. The registry does not describe event timing, follow-up duration, adjudication, or attribution in the information available for these figures.

Bronchopneumonia is listed among the serious adverse event terms at 1.2%. The record does not establish which group this term belongs to in the information presented. The listed serious-event counts do not describe all adverse events: the other-event counts are separate and should not be conflated with serious adverse events.

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

The record establishes that this randomized, parallel-group Phase 3 trial was designed to assess immune memory after DTPw-HBV/Hib priming and to assess immunogenicity and reactogenicity of booster strategies. Its primary endpoint is defined as the number of participants meeting two anti-PRP antibody thresholds at Month 1 after the PRP challenge. The record also identifies the ATP immunogenicity cohort used for the primary analysis.

Those design details do not reveal the trial’s primary findings. The registry record does not report the anti-PRP counts, denominators, group comparisons, or uncertainty intervals. Without those results, it is not possible to describe the observed response, compare groups, or evaluate the precision of an estimated difference. The record’s completed status and enrollment figure do not fill that gap.

The listed secondary outcomes and serious adverse event figures provide additional context, but they do not answer the primary immunogenicity question. The safety counts are limited to the groups and event categories listed, and the record does not provide all details needed to interpret their timing or attribution.

General statistical explanation: a trial result is an estimate from the analyzed data, not a guarantee of the same result in every setting. Its interpretation depends on the endpoint definition, analysis population, comparison, and precision. In this case, the endpoint definition is available, but the primary estimates and the analysis details needed to evaluate them are not reported in the registry record. No claim about whether any vaccine strategy does or does not work follows from the information posted.

13. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition is not the same as a reported result. The registry identifies a specific immunogenicity measure: counts of participants reaching anti-PRP thresholds at a defined time after challenge. That description allows readers to understand what was intended to be measured, but not what was observed.

It also highlights the importance of the analysis population. The primary population is described as an According-to-Protocol cohort of evaluable participants with immunogenicity data. Without group-specific denominators and information about exclusions or missing measurements, readers cannot assess how that cohort relates to all randomized participants. This distinction matters when interpreting counts or comparing groups.

The trial lists multiple outcomes and groups, which makes a prespecified primary comparison and a clear multiplicity strategy important for statistical interpretation. Neither is reported in the registry record. The safety information further demonstrates why event counts need context: counts by group are available, but timing, attribution, and follow-up details are not.

More broadly, a registry record can document a completed trial and its intended questions while still leaving the main statistical findings unavailable. Transparent reporting of estimates, denominators, uncertainty intervals, analysis populations, and missing-data methods is essential for readers to judge both the magnitude and precision of a result. In this record, those details are not reported for the primary 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 main limitation for interpreting this trial is that the registry record does not report analyses for the primary endpoint. It specifies the antibody thresholds and measurement time but gives no observed counts, group denominators, comparison estimates, confidence intervals, or p-values. The record lists zero analyses, so the primary question cannot be answered using the posted results.

The intervention and arm descriptions are not fully detailed. Some descriptions identify priming and challenge schedules but end before specifying the full booster regimen. The registry record does not report a single prespecified primary comparison, allocation ratio, or complete account of the randomization procedure. No masking is recorded.

The analysis population is described as the ATP immunogenicity cohort, but the record does not report its size by group, the criteria for evaluability, exclusions, or missing-data handling. This prevents assessment of how the analyzed participants relate to the randomized population. The registry also does not report a multiplicity plan despite listing 29 outcome measures.

Safety information is limited to the listed event counts and a serious adverse event term. Details about event timing, follow-up, attribution, and adjudication are not reported in the registry record. These reporting gaps limit statistical interpretation; they should not be mistaken for evidence about unreported outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immune Memory of DTPw-HBV/Hib Vaccine Following Primary Vaccination, Immuno & Reacto of a Booster Dose Given in Infants — NCT00169442.
• Registry record last updated 2018-06-06; status last verified 2017-05.
• Results first posted 2017-02-28.
• 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

NCT00169442 is a completed, randomized, parallel-group Phase 3 trial sponsored by GlaxoSmithKline. It enrolled 745 participants and recorded no masking. The trial examined immune memory after DTPw-HBV/Hib primary vaccination and the immunogenicity and reactogenicity of booster strategies, including a plain PRP challenge at 10 months for some groups and boosters at 15-18 months.

The primary endpoint was the count of participants meeting anti-PRP antibody thresholds at Month 1 after the PRP challenge. The stated analysis population was the According-to-Protocol cohort for immunogenicity. The registry record lists 29 outcome measures but zero analyses, and does not report the primary endpoint results or statistical comparisons. Serious adverse event counts are listed for several groups, with 0 deaths in each reported group.