Comparison of DTaP-IPV-Hep B-PRP~T Combined Vaccine to CombAct-HIB® Concomitantly Given With Engerix B® Paediatric and OPV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of DTaP-IPV-Hep B-PRP~T Combined Vaccine to CombAct-HIB® Concomitantly Given With Engerix B® Paediatric and OPV (NCT00362336), a randomized phase 3 study. The primary outcome is Number of Participants With Seroprotection After Primary Series Vaccination With DTaP-IPV-Hep B-PRT~T or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV).

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group phase 3 study. The registry reports enrollment of 622 and lists three groups: DTaP-IPV-Hep B-PRP~T; CombAct-HIB with Engerix B and OPV; and DTaP-IPV-Hep B-PRP~T with Engerix B at birth. The listed primary vaccination schedule was at 6, 10, and 14 weeks of age. The registry identifies the study as completed, with a start in 2006-08 and primary completion in 2008-05.

The primary objective concerned immune response one month after the third dose. The stated comparison was whether the combined vaccine did not induce lower immune responses than the separate-vaccine regimen, assessed through seroprotection measures. The study also aimed to describe safety, including adverse events during the first 28 days after each injection and serious adverse events during the trial. Secondary objectives concerned immune responses after the primary series and before and after a booster vaccination.

Random allocation can help balance baseline characteristics across groups, on average, but the registry record does not describe the randomization procedure, allocation concealment, or group assignment details. Masking is listed as none. The record does not report further protocol details about blinding of laboratory assessments or outcome evaluation, so those procedures cannot be inferred. The primary analysis population is described as per protocol, rather than all enrolled participants. The number included in that population is 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: A total of 622 of the 715 recruited participants who met the inclusion and exclusion criteria were enrolled and vaccinated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Seroprotection was assessed in all participants who did not have any protocol violation that might have interfered with primary criteria evaluation (Per-Protocol Population).

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 Participants With Seroprotection After Primary Series Vaccination With DTaP-IPV-Hep B-PRT~T or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV), measured over 1 month post-Dose 3.

The primary endpoint counts participants meeting seroprotection criteria after the primary series, with assessment one month after Dose 3. Seroprotection is a threshold-based measure: each participant’s antibody result is classified according to whether it meets a stated level for an antigen. The registry lists criteria for tetanus, diphtheria, hepatitis B, PRP, and poliovirus types 1, 2, and 3. Antibodies were assessed using different laboratory methods for the different antigens.

Threshold outcomes are commonly used in vaccine immunogenicity studies because they translate measured antibody levels into the proportion of participants who reach a prespecified response level. As a general statistical point, that classification is easier to interpret as a response rate than a continuous antibody value, but it also discards information about how far a result lies above or below the threshold. The registry additionally lists geometric mean titers and other seroprotection or seroconversion outcomes as secondary measures.

The registry record describes the endpoint and its thresholds but does not provide the primary counts, rates, between-group estimates, confidence intervals, or test results. It therefore does not allow a numerical assessment of how closely the groups’ seroprotection results compared.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a seroprotection count represent?

Each participant’s antibody measurement is compared with a threshold specified for the antigen. A participant at or above that threshold is counted as seroprotected for that measure; the group result is then expressed as a count or proportion, depending on the reported analysis. This is a binary outcome because each individual is classified into one of two categories for a given threshold. The registry gives thresholds for tetanus and diphtheria of at least 0.01 International Unit (IU)/mL, hepatitis B of at least 10 mIU/mL, PRP of at least 0.15 µg/mL, and poliovirus types 1, 2, and 3 of at least 8 (1/dil).

As a general statistical point, a binary endpoint summarizes whether a criterion is met, not the size of the antibody response beyond that criterion. A separate continuous measure, such as a geometric mean titer, can describe the distribution of antibody levels in a different way. The registry lists geometric mean titers among the secondary outcomes, but does not report their numeric results.

How should the non-lower-response objective be understood?

The primary objective asks whether immune responses with one regimen are not lower than responses with another. In general, a formal non-inferiority analysis compares a between-group effect estimate with a prespecified margin. The margin defines how much lower a response could be while still satisfying the study’s criterion. A confidence interval is typically important because it reflects uncertainty around the estimated difference. The registry record does not report the margin, the analysis method, an estimate, or a confidence interval; these details cannot be reconstructed from the stated objective alone.

As a general statistical distinction, failure to detect a difference is not the same as demonstrating non-inferiority. The latter requires evidence tied to the prespecified margin and analysis. Since the primary results and relevant decision criteria are not reported in the registry record, no such determination can be made from the record.

Why does the analysis population matter?

The primary endpoint description specifies a per-protocol population, excluding participants with protocol violations that might interfere with primary criteria evaluation. As a general principle, this can focus analysis on participants who followed key study procedures, but it also means the analyzed group may differ from all randomized or enrolled participants. For non-inferiority questions, the choice of population and handling of deviations can influence interpretation. The registry does not report the size of the per-protocol population, the exclusions, or a complementary analysis in another population.

What do the safety counts say statistically?

The safety record gives group-specific counts of participants at risk and participants with serious adverse events, and counts for other adverse events. These are event-count summaries, not adjusted comparisons. A difference between group counts cannot be interpreted without considering denominators, definitions, follow-up, and uncertainty. As a general statistical point, sparse serious-event counts often yield imprecise comparisons; the record does not provide comparative estimates or confidence intervals for these safety summaries. The listed serious-event terms and percentages are descriptive and do not establish that a vaccine caused an event.

What do planning calculations mean?

Any sample-size planning illustration is distinct from the study’s observed results. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is framed as a stated fraction of the observed effect. These are planning assumptions, not evidence about the original protocol’s design or justification. The registry record does not report the original sample-size justification or planned statistical analysis. Planning estimates should not be described as observed power, and they do not recover missing endpoint results.

The record lists zero analyses, so it does not provide formal analysis outputs for the primary endpoint. General explanations of binary outcomes, confidence intervals, and non-inferiority methods describe how such analyses are usually interpreted; they do not establish which exact procedures were used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome contains multiple antigen-specific measures: the registry names diphtheria, tetanus, polio, hepatitis B, and PRP, and gives separate thresholds for poliovirus types 1, 2, and 3. The record does not reduce these components to a single reported comparison. When several outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested separately. As a general statistical point, prespecified testing strategies or multiplicity adjustments can address that issue, but the registry record does not report whether either was used.

The record lists secondary outcomes covering additional seroprotection and seroconversion titers, geometric mean titers, pre-booster persistence, post-booster responses, and solicited reactions after primary and booster vaccination. It does not report a hierarchy of hypotheses, multiplicity procedures, or results for these outcomes. The number of outcome measures is listed as 7, but that does not establish how they were prioritized or tested.

Missing-data methods are not reported in the registry record. The primary population definition excludes protocol violations that could interfere with evaluation, but the record does not describe how missing antibody measurements, missed visits, withdrawals, or other incomplete observations were handled. Nor does it report the number missing for each endpoint or reasons for missingness. As a general statistical point, missing-data handling can affect estimates when availability of measurements is related to participant characteristics or outcomes.

The analysis population for the primary endpoint is described as per protocol. The record does not give its size, exclusions, or an intention-to-treat result for comparison. With no primary analysis outputs, readers cannot assess how population choice, missing observations, or multiple outcomes influenced the reported conclusion.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5.00% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchopneumonia (1.5%), gastroenteritis (0.8%), dysentery (0.8%), ventricular septal defect (0.7%), bronchiolitis (0.7%).

The safety record lists three groups and reports participants at risk and participants with serious adverse events: 243 at risk and 7 affected in the DTaP-IPV-Hep B-PRP~T group; 242 at risk and 6 affected in the CombAct-Hib, Engerix B, and OPV group; and 137 at risk and 5 affected in the combined-vaccine group with Engerix B at birth. It also lists participants with other adverse events: 202, 210, and 119, respectively. These are descriptive counts, not adjusted comparisons.

The record lists serious-event terms with percentages: bronchopneumonia (1.5%), gastroenteritis (0.8%), dysentery (0.8%), ventricular septal defect (0.7%), bronchiolitis (0.7%), and lobar pneumonia (0.7%). It does not report the counts or group attribution for each term in this summary, nor the denominator used for each percentage. Deaths are not reported in the registry record.

As a general statistical point, adverse-event counts describe events observed and recorded during a study; by themselves, they do not establish causation or provide a precise comparison between regimens. The registry record does not report comparative safety estimates or uncertainty intervals for these figures.

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

The registry record establishes the trial’s purpose, broad design, primary endpoint definition, and the existence of safety summaries. It states that the primary question concerned seroprotection one month after Dose 3, comparing the combined vaccine with CombAct-HIB plus Engerix B Paediatric and OPV. It also describes a group receiving the combined vaccine with Engerix B at birth and lists secondary immune-response and safety outcomes.

The record does not report numeric results for the primary seroprotection outcome. It therefore does not show the group-specific response counts or proportions, the size of any between-group difference, or the precision of that comparison. No non-inferiority margin or primary analysis result is reported in the registry record. The stated objective cannot be treated as a result, and the absence of a reported result is not evidence that the groups were the same or different.

The safety figures are descriptive. They report counts of participants with serious and other adverse events, alongside selected serious-event terms and percentages. They do not, on their own, establish whether events were caused by a vaccine, whether rates differed meaningfully between groups, or how precisely any difference was estimated. Additional contextual information, such as term-specific denominators and comparative analyses, is not reported in the registry record.

As a general statistical point, a trial’s design describes how evidence was intended to be collected; a result requires the relevant observations and analysis. The registry record supports a description of the research question and endpoint, but not a numerical conclusion about comparative immune responses. It also does not provide enough information to evaluate the planned statistical approach or the effects of missing data and analysis-population choices.

13. Why This Trial Matters Statistically

This trial presents a common statistical challenge in vaccine research: the primary question concerns whether immune responses after a combined vaccine are not lower than responses after a comparator regimen. Such a question depends on more than observing similar-looking group results. It requires a clear margin for acceptable difference, an analysis suited to the design, and an estimate with enough precision to assess that margin. The registry record states the objective but does not report those decision elements or the primary analysis results.

The endpoint also spans several antigen-specific responses. Each threshold translates a laboratory measurement into a classification, and each antigen can have its own result and uncertainty. A broad statement about immune response should not conceal variation among antigens. The registry’s descriptions of thresholds and secondary antibody measures illustrate why endpoint definition matters, while the absence of numeric results prevents examination of those patterns.

The population definition matters as well. The primary outcome is assigned to a per-protocol population, while the record does not report its size or provide other analysis-population results. In general, readers need to know who contributed to each estimate and how incomplete observations were handled to judge how robust an inference may be.

Finally, safety counts and immunogenicity results answer different questions. Descriptive adverse-event counts can characterize reported events, but they cannot substitute for the immune-response comparison or establish causation. The record is statistically informative about the question, design, and endpoint definitions, but its missing primary results sharply limit what can be concluded about the comparison.

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 trial-specific limitation in the registry record is the absence of numeric primary outcome results. No group-specific seroprotection counts or proportions, comparison estimates, confidence intervals, or test results are reported. The stated non-lower-response objective cannot be evaluated without these results and the decision criteria used for the comparison.

The record describes a per-protocol primary population but does not report its size, participant flow, protocol deviations, or the number assessed for each antigen. It does not state how missing measurements were handled, whether additional analysis populations were assessed, or how withdrawals and incomplete follow-up affected the analysis. These omissions limit assessment of the population represented by any intended result.

The study had multiple antigen-specific and secondary outcomes, but the registry does not report a testing hierarchy, multiplicity approach, or complete numeric results for those outcomes. The registry also does not report the non-inferiority margin, sample-size justification, or full statistical analysis plan. Planning assumptions in an illustrative sample-size calculation are not evidence of the trial’s original design rationale.

For safety, the registry lists event counts and selected serious-event terms, but does not report term-specific counts and denominators in the summary, comparative estimates, or uncertainty intervals. Deaths are not reported in the registry record. These limitations mean the safety descriptions cannot support a precise comparative assessment. The record also lists no analyses, leaving the reported endpoint definitions without corresponding formal analysis outputs.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of DTaP-IPV-Hep B-PRP~T Combined Vaccine to CombAct-HIB® Concomitantly Given With Engerix B® Paediatric and OPV — NCT00362336.
• Registry record last updated 2014-05-02; status last verified 2014-04.
• Results first posted 2014-05-02.
• 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

This completed randomized, open-label, parallel-group phase 3 study enrolled 622 South African infants. It compared DTaP-IPV-Hep B-PRP~T with CombAct-HIB, Engerix B Paediatric, and OPV on a schedule at 6, 10, and 14 weeks, and included a group receiving the combined vaccine with Engerix B at birth.

The primary endpoint was the number of participants with seroprotection one month after Dose 3, assessed in a per-protocol population. Secondary outcomes covered antibody measures, booster responses, and adverse events. The registry record reports safety counts and selected serious-event terms, but does not report numeric primary immunogenicity results, comparative estimates, confidence intervals, or the analysis plan.