Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared With PENTAXIM™ and ENGERIX B® PEDIATRICO in Argentinean Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared With PENTAXIM™ and ENGERIX B® PEDIATRICO in Argentinean Infants (NCT00831311), a randomized phase 2 study. The primary outcome is Percentage of Participants With Seroconversion for Anti-pertussis Toxoid and Anti-filamentous Hemagglutinin Antibodies Post-vaccination With Either DTaP-IPV-Hep B-PRP~T or PENTAXIM™ and ENGERIX B®.

2. Clinical Question

This is an immunogenicity comparison, not a direct comparison of clinical disease outcomes. Seroconversion is an antibody-based measure defined in the registry as an increase in titer from baseline after vaccination. The study also set out to describe immunogenicity parameters and safety in each group. The registry lists outcomes for solicited injection-site and systemic reactions, but the primary objective centers on immune response after the series.

3. Trial Design

This was a randomized, parallel-group phase II study in healthy Argentinean infants. The record gives an enrollment of 624 and describes two groups: one received DTaP-IPV-Hep B-PRP~T, and the other received PENTAXIM™ and ENGERIX B®. The study was conducted in Argentina. Its recorded start was 2004-10, primary completion was 2005-11, and its status is completed.

The vaccination schedule in the official title specifies doses at 2, 4, and 6 months of age. The primary immunogenicity assessment took place 1 month after the last vaccination. Randomization supports a planned comparison between the assigned regimens, but the registry does not report the allocation method, whether allocation was concealed, or the details of how randomization was implemented. Masking is listed as none, so the trial was not masked according to the record.

The primary objective was to demonstrate non-inferiority of the combined vaccine’s immune response for all valences relative to the association of the two comparator vaccines. Secondary objectives were to describe immunogenicity after the series and safety after each vaccination. The registry lists seven outcome measures, including solicited reactions, but reports zero analyses in its analysis information. Detailed statistical methods, analysis populations beyond the primary endpoint’s per-protocol population, and a non-inferiority margin are not reported in the registry record.

The enrollment figure is not itself evidence that all enrolled participants completed vaccination or contributed to the primary analysis. Counts completing follow-up, exclusions, and reasons for exclusion are not reported in the registry record. Those details matter because the primary endpoint was assessed in a per-protocol population rather than being described as an analysis of every randomized participant.

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 624 participants who met the inclusion but no 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: Seroconversion for anti-pertussis toxoid and anti-filamentous hemagglutinin antibodies was assessed in the 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 Percentage of Participants With Seroconversion for Anti-pertussis Toxoid and Anti-filamentous Hemagglutinin Antibodies Post-vaccination With Either DTaP-IPV-Hep B-PRP~T or PENTAXIM™ and ENGERIX B®, measured over 1 month post last vaccination.

The primary endpoint is the percentage of participants with seroconversion for antibodies to pertussis toxoid (PT) and filamentous hemagglutinin (FHA), assessed 1 month after the last vaccination. The registry says antibody levels were measured by enzyme immunoassay. Seroconversion was defined as at least a 4-fold increase in antibody titers from Day 0 to 30 days after the third vaccination. Assessment was in the per-protocol population.

These antibody measures provide an immunogenicity endpoint: they describe a measured immune response rather than directly counting cases of pertussis or another disease. The trial’s primary objective frames the comparison as non-inferiority across all valences, while the named primary outcome specifically identifies PT and FHA seroconversion. How the endpoint related to the broader all-valence objective, including the specific decision rule for non-inferiority, is not reported in the registry record.

For a percentage endpoint, the basic quantity is the proportion of participants meeting the seroconversion definition among those assessed. A comparison needs the group-specific results and a prespecified interpretation rule. The registry record does not report the primary endpoint percentages, their uncertainty, a between-group estimate, or a non-inferiority margin. Consequently, the endpoint’s definition can be described, but the registry record does not permit a conclusion about the study’s primary comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The principal outcome is binary at the participant level: each assessed participant either meets the seroconversion definition or does not. A group percentage expresses the share meeting that definition. This kind of endpoint differs from a continuous antibody-titer comparison, which would retain the numerical titer values rather than classify participants using a threshold. The registry identifies the percentage of participants with seroconversion, but the group percentages are not reported in the registry record.

What does the seroconversion definition do?

The definition classifies a participant based on the change in antibody titer between Day 0 and 30 days after the third vaccination. A threshold makes the outcome interpretable as a response category, but it also discards information about the size of increases beyond that threshold and about changes that fall short of it. This is a general feature of dichotomizing a continuous measurement. It does not mean the threshold is inappropriate; it means the percentage should be interpreted as the frequency of meeting a defined criterion, rather than as a complete description of antibody levels.

The registry specifies enzyme immunoassay for anti-PT and anti-FHA antibodies, and places the assessment 1 month after the last vaccination. It does not report assay performance characteristics, laboratory quality-control procedures, or individual antibody distributions. Those details would help readers understand measurement variability, but their absence does not alter the endpoint definition stated in the record.

How is non-inferiority usually assessed?

In general, a non-inferiority analysis compares an estimate of the difference between treatment groups with a prespecified margin. The margin defines how much lower the response could be in the experimental group while still meeting the criterion. The interpretation depends on the direction of the comparison, the chosen confidence interval or testing procedure, and the margin specified before outcome data are assessed. A narrow interval can support a more precise conclusion than a wide interval, but only when interpreted against the margin.

The registry states that the objective was to demonstrate non-inferiority for all valences. It does not report the margin, the direction and form of the statistical contrast, the confidence level, or the testing procedure. It also does not report the primary outcome estimate or an interval. General principles can explain what information a non-inferiority conclusion requires, but they cannot substitute for the missing trial-specific result.

In a binary outcome analysis, an effect may be expressed using a difference in percentages or another measure of relative frequency. Each measure answers a different question and can have a different numerical interpretation. The registry record does not report which measure was used for the primary comparison. No unadjusted recalculation can be described because the relevant group-specific primary outcome counts and percentages are not reported.

Why do confidence intervals matter?

As a general statistical concept, a confidence interval describes the range of values compatible with the observed data under the assumptions of the analysis. It conveys precision as well as direction: an estimate alone does not show how uncertain it is. For non-inferiority, the interval is judged relative to the prespecified margin, not simply by whether it includes a null value. Neither the interval nor the margin is reported in the registry record, so the precision of the primary comparison cannot be evaluated.

What can planning calculations say?

Sample-size calculations are prospective planning tools. The registry describes a planning illustration based on a fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such calculations depend on their assumptions and are not a measure of the trial’s observed power. They do not show whether the study achieved its objective, and they cannot replace a reported treatment-effect estimate with uncertainty.

The planning illustration is described as based on the observed effect, but that effect and the resulting participant counts for planning are not reported in the registry record. The trial’s original sample-size assumptions and justification are also not reported. In general, planning for an effect smaller than the observed effect requires more information to detect that smaller effect, but no trial-specific quantity can be inferred without the stated effect and other calculation inputs.

How should multiple outcomes be considered?

Multiple endpoints, antibody measures, time points, or repeated safety assessments create opportunities for selective emphasis and increase the importance of a prespecified analysis plan. The registry lists several outcomes, including safety outcomes after vaccination, while the primary objective refers to all valences. It does not report a multiplicity adjustment, a hierarchy of tests, or a strategy for handling multiple comparisons. These are not details that can be reconstructed from the outcome titles alone.

For safety outcomes, percentages and counts are descriptive unless a comparative analysis is specified and reported. Solicited reactions may be collected repeatedly after vaccinations, so interpretation depends on the time window, whether participants are counted once or at each assessment, and how missing reports are handled. The registry’s outcome descriptions mention reactions following each vaccination, but detailed analysis methods for these outcomes are not reported in the registry record.

All statistical interpretation is conditional on how participants were selected for analysis and how missing measurements were handled. A per-protocol population is named for the primary endpoint, but its definition, size, and relationship to the randomized groups are not reported. General methods can clarify what an endpoint or uncertainty interval means; they cannot resolve those trial-specific omissions.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary objective involving non-inferiority for all valences, names a primary outcome focused on anti-PT and anti-FHA seroconversion, and lists secondary immunogenicity and safety objectives. It does not report how multiplicity was addressed. In general, testing several outcomes or making several comparisons can raise the chance that at least one result appears noteworthy by chance. A prespecified testing hierarchy, adjustment, or other strategy can clarify how such evidence is to be interpreted. No such strategy is reported in the registry record.

The primary endpoint population is identified as per-protocol. The registry does not define the per-protocol criteria, give the number of participants analyzed, or report how participants moved from enrollment to analysis. It also does not report an intention-to-treat analysis or whether more than one analysis population was used. These omissions are relevant to a non-inferiority question, for which conclusions can depend on analysis population and protocol adherence.

Missing-data methods are not reported in the registry record. The record does not state how missing antibody measurements, incomplete vaccination, withdrawal, or other unavailable assessments were handled. In general, complete-case results describe participants with observed measurements and may not represent all randomized participants if missingness is related to response or treatment group. Imputation or sensitivity analyses can address assumptions about missing outcomes, but no such procedures are described in the record.

The registry reports zero analyses in its analysis information. This does not establish that no analyses were conducted; it means that analyses are not documented in that part of the registry record. The primary result, analysis plan, multiplicity strategy, and missing-data approach are not reported in the registry record, limiting evaluation of the prespecified comparison and the robustness of any 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: bronchiolitis (2.9%), pneumonia (1.3%), gastroenteritis (1.0%), bronchitis (1.0%), urinary tract infection (1.0%).

The registry lists 311 participants at risk in the combined-vaccine group and 312 in the PENTAXIM™ and ENGERIX B® group for serious adverse event reporting. It records 19 affected participants in the first group and 22 in the second. For other adverse events, the corresponding at-risk counts are 311 and 312, with 305 and 307 affected participants. These are reported counts; they should not be converted into a causal conclusion about either regimen.

The serious adverse event terms listed include Bronchiolitis at 2.9%, Pneumonia at 1.3%, Gastroenteritis at 1.0%, Bronchitis at 1.0%, Urinary Tract Infection at 1.0%, and Convulsion at 0.6%. The registry record does not provide participant counts or denominators for each listed term, or state whether participants could contribute more than one event. It also does not report a comparative statistical analysis or attribution of these events to vaccination.

Deaths are recorded as null for both groups; this is not a reported zero count. Serious adverse event counts and listed terms are descriptive registry information. They do not, on their own, establish that an event was caused by vaccination or that a difference between groups is meaningful.

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

The record documents a randomized phase II comparison of an all-in-one vaccine regimen with PENTAXIM™ and ENGERIX B® in healthy Argentinean infants. Its central statistical aim was non-inferiority of immune response after the primary series. The record also defines a seroconversion endpoint and identifies a per-protocol population for that endpoint. These details explain what the study was designed to assess.

The record does not report the primary endpoint results. It gives no group-specific seroconversion percentages, between-group estimate, confidence interval, non-inferiority margin, or statistical decision. As a result, the registry record cannot establish whether the non-inferiority objective was met or how precisely the groups’ immune responses were compared. This absence of results is not evidence that the groups were equivalent, nor is it evidence that they differed.

Seroconversion is an antibody response measure, not a direct count of clinical disease. Even a reported antibody comparison would need to be interpreted according to the endpoint definition and the prespecified decision rule. The registry’s definition uses a threshold for change from baseline, but it does not provide the underlying titers or the trial-specific statistical analysis required to interpret the primary objective.

The safety counts and serious adverse event terms offer descriptive information, but they are not a complete comparative safety analysis. The record does not include event attribution or detailed comparative inference, and the null death entries do not establish a zero count. The listed counts should therefore not be treated as proof that an intervention caused or did not cause an event.

More broadly, a completed study status indicates that the trial is recorded as completed, not that its primary question has been resolved in the posted results. The absence of reported analyses, participant flow, and methods for missing data and multiplicity leaves important uncertainty about how the intended comparison would be evaluated. Interpretation should remain limited to the design and outcome descriptions that the registry record actually documents.

13. Why This Trial Matters Statistically

This trial illustrates a common distinction in clinical research: a stated objective is not the same as a reported result. The record clearly sets out a non-inferiority aim for immune responses, but does not report the primary outcome values or the analysis needed to assess that aim. For statistical readers, this is a reminder to separate trial design, endpoint definition, and evidence from the observed comparison.

It also highlights the importance of a prespecified non-inferiority margin. An outcome can be measured precisely yet remain difficult to interpret if the acceptable difference and analysis rule are not reported. A claim of non-inferiority depends on the relationship between an estimated contrast, its uncertainty, and the margin. Those elements cannot be inferred from a trial title or objective statement.

The endpoint provides another useful teaching example. Seroconversion turns an antibody change into a participant-level binary outcome, which supports reporting a percentage but does not retain the full pattern of antibody values. Understanding what the endpoint counts, when it is measured, and which population is analyzed is essential before considering a group comparison.

The record also brings attention to analysis populations and safety reporting. The primary endpoint is specified for a per-protocol population, but the participant flow and criteria are not available. Safety counts and selected terms are reported descriptively, without the information needed to assess attribution or comparative uncertainty. Across immunogenicity and safety, transparent reporting of denominators, analytic methods, and uncertainty is necessary for readers to distinguish a descriptive summary from a supported statistical conclusion.

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.

Several limitations are specific to the information recorded for this trial. The primary seroconversion percentages and comparative result are not reported in the registry record, even though the endpoint definition and non-inferiority objective are described. The non-inferiority margin, comparison measure, confidence interval, and decision rule are also not reported, so the primary question cannot be statistically resolved from the record.

The record names a per-protocol population but does not define it or state how many participants were included. It reports enrollment of 624, but not the number randomized to each group, the number completing the series, or reasons for exclusions and missing assessments. The impact of departures from protocol or missing antibody results therefore cannot be assessed.

Masking is listed as none. This is relevant to solicited reactions, which can be influenced by reporting and assessment, although the registry does not describe assessor procedures. Laboratory measurement is identified as enzyme immunoassay, but laboratory masking, assay performance, and quality-control details are not reported. Allocation concealment and the detailed randomization process are also not reported.

The record lists safety counts and selected serious adverse event terms but does not give term-specific counts and denominators, attribution, or comparative analyses. Death entries are null rather than reported counts. The record does not describe multiplicity control, missing-data methods, interim analyses, or the trial’s sample-size justification. These limitations concern reporting in the registry record and should not be mistaken for proof that a method was or was not used in the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared With PENTAXIM™ and ENGERIX B® PEDIATRICO in Argentinean Infants — NCT00831311.
• Registry record last updated 2013-12-17; status last verified 2013-11.
• Results first posted 2013-11-21.
• 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

NCT00831311 is a completed randomized phase II parallel-group study in healthy Argentinean infants, with enrollment of 624. It compared DTaP-IPV-Hep B-PRP~T with PENTAXIM™ and ENGERIX B® for a three-dose series at 2, 4, and 6 months of age. Masking is listed as none.

The primary objective was non-inferiority of immune response across valences. The named primary endpoint was seroconversion for anti-PT and anti-FHA antibodies 1 month after the last vaccination, assessed in the per-protocol population. The endpoint definition uses enzyme immunoassay and a threshold of at least a 4-fold titer increase from Day 0 to 30 days after the third vaccination.

Safety outcomes include solicited reactions, and the registry lists serious and other adverse event counts. The primary endpoint results, non-inferiority margin, analysis methods, missing-data approach, and multiplicity strategy are not reported in the registry record.