Study Comparing a DTaP-HB-PRP~T Combined Vaccine With Tritanrix HepB/Hib™, Concomitantly With OPV in Healthy Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Comparing a DTaP-HB-PRP~T Combined Vaccine With Tritanrix HepB/Hib™, Concomitantly With OPV in Healthy Infants (NCT00348881), a randomized phase 3 study. The primary outcome is Number of Participants With Seroprotection for Anti-Hep Bs, Anti-PRP, Anti-Tetanus, and Anti-Diphtheria Antibodies After Vaccination With Either DTaP-Hep B-PRP~T Concomitantly With OPV or Tritanrix-Hep B/Hib™ Concomitantly With OPV.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, quadruple-masked, parallel-group study. Its stated purpose was to compare the safety and immune response of DTaP-Hep B-PRP-T combined vaccine with Tritanrix-HepB/Hib™, with both regimens given concomitantly with OPV. The registry lists an enrollment of 2133 and a completed status.

Participants were healthy Filipino infants. In the intervention group, participants received DTaP-Hep B-PRP-T and OPV at 6, 10, and 14 weeks of age. In the comparator group, participants received Tritanrix-HepB/Hib™ and OPV at the same ages. The parallel design means the two regimens were assigned to separate groups rather than given sequentially to the same participants. Randomization is intended, in general, to reduce systematic differences between groups at the point of assignment. The registry record does not report the randomization procedure or allocation concealment details.

The registry identifies quadruple masking, but does not specify in the record which roles were masked or how masking was maintained. Additional design details, including the protocol’s sample-size justification, are not reported in the registry record. The listed study timing runs from 2006-06 to primary completion in 2007-10; the record marks the study completed.

The primary outcome assessed seroprotection for four antibody types 1 month after the third vaccination. Secondary outcomes included geometric mean titers of vaccine antibodies and the number of participants reporting at least one solicited injection-site or systemic reaction following vaccination. These outcome categories address immune measurements and reported reactions; they are not themselves evidence of a difference between regimens. Results for the primary endpoint comparison are 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 2133 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 a subset of participants available for the endpoint, 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 Number of Participants With Seroprotection for Anti-Hep Bs, Anti-PRP, Anti-Tetanus, and Anti-Diphtheria Antibodies After Vaccination With Either DTaP-Hep B-PRP~T Concomitantly With OPV or Tritanrix-Hep B/Hib™ Concomitantly With OPV, measured over 1 month post third vaccination.

The primary endpoint counts participants meeting seroprotection criteria for anti-Hep Bs, anti-PRP, anti-tetanus, and anti-diphtheria antibodies, measured 1 month after the third vaccination. For this endpoint, seroprotection was defined as titers ≥ 10 mIU/mL for anti-Hep Bs, ≥ 0.15 μg/mL for anti-PRP, and ≥ 0.01 IU/mL for both anti-tetanus and anti-diphtheria. The record specifies radioimmunoassay for anti-Hep Bs and anti-PRP, enzyme immunoassay for anti-tetanus, and serum neutralization for anti-diphtheria.

Seroprotection is a threshold-based immunologic measure: it classifies whether a measured antibody titer meets the specified cutoff. Such an endpoint can describe the proportion or count reaching a defined antibody level, but it does not directly measure clinical illness. The four antibody categories also represent distinct measurements, with different assays and thresholds; they should not be treated as one interchangeable antibody result.

The registry specifies that the primary endpoint was assessed in a per-protocol subset available for the endpoint. The size of that subset, the number meeting each threshold, and the statistical comparison are not reported in the registry record. Therefore, the endpoint definition is available, but its observed group results and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching a method to the outcome and the question. The primary outcome in this study is a count of participants who meet antibody-specific seroprotection thresholds. In general, a binary outcome classifies each assessed participant as meeting or not meeting a criterion. Group summaries can then describe how many participants met the criterion, while a comparative analysis estimates how those outcomes differ between groups. The registry record does not report the group results or the method used for a primary comparison.

What does seroprotection measure?

The endpoint applies a cutoff to an antibody titer. A titer at or above the relevant threshold is classified as seroprotected for that antibody. This makes the endpoint clinically and statistically different from a continuous titer measurement: the threshold classification discards information about how far a measured value lies above or below the cutoff. The listed secondary outcome of geometric mean titers retains a continuous summary of antibody levels, but results for that outcome are not reported in the registry record.

The four primary antibody categories have distinct thresholds and assays. The registry describes radioimmunoassay for anti-Hep Bs and anti-PRP, enzyme immunoassay for anti-tetanus, and serum neutralization for anti-diphtheria. Because both the measurements and cutoffs differ, each category needs to be interpreted on its own terms. The record does not provide a single combined endpoint definition that would justify treating all four categories as one numerical outcome.

Why does the analysis population matter?

The primary outcome was assessed in a subset of participants available for the endpoint, identified as the per-protocol population. In general, a per-protocol analysis focuses on participants meeting specified protocol requirements. It can describe outcomes among those participants, but its interpretation depends on which requirements were applied and who was excluded or unavailable. The record does not report the size of the per-protocol subset, the reasons participants were not assessed, or the precise analysis rules. The resulting potential for selection effects therefore cannot be evaluated from the registry record.

Randomization is generally used to make treatment groups comparable at assignment. However, an analysis restricted to participants with available endpoint data may no longer preserve all the protections of the original randomization if availability or protocol adherence is related to outcome or group. This is a general consideration, not evidence that such a problem occurred in this study. The registry record does not report enough detail to assess it.

What would an uncertainty interval add?

For a group difference, a confidence interval expresses uncertainty around the estimated effect under the statistical model. In general, an interval that is narrow indicates greater precision than a wide interval, while an interval that includes values on both sides of no difference may leave the direction of the effect uncertain. A p-value addresses compatibility of the data with a specified null model, but is not a measure of effect size or clinical importance. The registry record does not report a primary estimate, confidence interval, or p-value, so these concepts cannot be applied to an observed primary result.

With several antibody categories, interpreting multiple comparisons also requires care. In general, testing several outcomes can increase the chance of at least one apparently notable result if each is assessed separately without accounting for multiplicity. An analysis plan may specify a hierarchy, adjustment, or other approach, but no such plan is reported in the registry record. The record also says the primary outcome has several categories or time points and was not reduced to one comparison, so a single summary test should not be inferred.

How should safety counts be understood?

Safety summaries count participants with events, as reflected in the registry’s description of the outcome type. A count is a descriptive quantity and does not alone provide a comparison adjusted for uncertainty, follow-up, event severity, or differences in observation. In general, a complete interpretation also depends on the definition of an event, how events were collected and coded, the period of observation, and whether the same rules were used in each group. The record reports group counts and participants at risk but does not report these detailed methods or a statistical comparison for the adverse-event summaries.

Over-dispersion is a general issue when count data vary more than a simple statistical model expects; if present, it can make standard uncertainty estimates too small. It is not possible to assess over-dispersion from the adverse-event summaries in the registry record, and the record does not identify a count model for these data. Moreover, the reported safety summaries are participants with events rather than a posted analysis of event counts per participant, so a model for repeated event counts should not be assumed.

The registry includes an illustrative sample-size approach based on a stated fraction of the observed effect, with equal allocation, a two-sided significance level of 0.05, and a normal approximation. Such calculations are planning illustrations, not evidence that a particular sample size was justified in the trial protocol and not a measure of observed power. The protocol’s own sample-size justification and statistical plan are not reported in the registry record. No specific planning value should be treated as an observed study result.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint covers seroprotection for anti-Hep Bs, anti-PRP, anti-tetanus, and anti-diphtheria antibodies. The registry also notes several categories or time points and that the primary outcome was not reduced to one comparison. This structure raises a general multiplicity issue: when several outcomes or comparisons are examined, the chance of at least one nominally unusual finding can increase unless the analysis plan accounts for the number and relationship of tests. The registry record does not report a multiplicity strategy, a hierarchy among the antibody outcomes, or a prespecified single contrast.

Missing outcome information is a separate concern. The endpoint population is described as a per-protocol subset available for assessment, but the number assessed, the number missing, and reasons for missingness are not reported in the registry record. The record does not describe imputation, sensitivity analyses, or how participants without an endpoint measurement were handled. Without those details, it is not possible to assess whether endpoint availability could affect the comparison.

The record does not report the statistical analysis plan, including the primary estimand, the test or model for the binary endpoint, adjustment variables, or handling of protocol deviations. It also does not report whether interim analyses were planned or conducted. These items are not assumptions to fill in: they are not reported in the registry record. The disclosed per-protocol population definition is useful, but does not substitute for a full account of the analysis population and missing-data methods.

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: pneumonia (0.9%), gastroenteritis (0.6%), bronchopneumonia (0.3%), sepsis neonatal (0.1%), convlusion (0.1%).

The registry reports serious adverse-event counts of 31 among 1425 participants at risk in the DTaP-Hep B-PRP-T + OPV group and 12 among 708 at risk in the Tritanrix-Hep B/Hib™ + OPV group. For other adverse events, it reports 1092 among 1425 at risk and 636 among 708 at risk, respectively. These are descriptive participant counts, not a reported statistical test of a difference between groups. The registry does not provide confidence intervals or a comparative estimate for these summaries.

The listed serious-event terms include pneumonia (0.9%), gastroenteritis (0.6%), bronchopneumonia (0.3%), sepsis neonatal (0.1%), “Convlusion” (0.1%), and febrile convulsion (0.1%). The registry does not report the denominator or calculation basis for these percentages, so they should be read as registry-reported values rather than reinterpreted as group-specific risks. Death counts are not reported in the registry record.

In general, adverse-event counts do not establish that an event was caused by a vaccine, nor do they alone determine whether groups differ. Interpretation depends on definitions, ascertainment, timing, and analysis methods, details that are not reported in the registry record.

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

This study addresses a focused comparative question about antibody responses after two infant vaccine regimens, each administered with OPV on the same schedule. The primary endpoint was seroprotection for four antibody types at 1 month after the third vaccination. The registry record provides the thresholds and assays, allowing readers to understand what was intended to count as seroprotection.

However, an endpoint definition is not an endpoint result. The registry record does not report how many participants met each threshold in either group, a between-group estimate, or an uncertainty interval. It therefore does not establish whether the observed seroprotection levels were similar or different, how large any difference might have been, or how precisely it was estimated. No claim about the comparative immune response can be drawn from the primary results in this record.

The safety information offers descriptive counts of participants with serious and other adverse events, as well as selected serious-event terms and registry-reported percentages. These figures can describe what the record lists, but without a reported comparative analysis and further information about event definitions and observation, they do not establish causality or a reliable difference in safety between regimens. The record does not report death counts.

In general, a randomized design supports a comparative interpretation when outcomes are completely and appropriately analyzed, but randomization alone does not supply missing results or clarify unreported analysis choices. The per-protocol endpoint population also means that interpretation depends on which participants were included and how endpoint availability was handled; those details are not reported in the registry record.

The distinction is between what the record establishes and what it leaves unresolved. It establishes the trial design, dosing schedule, antibody criteria, and selected safety counts. It does not provide the primary endpoint comparison, its statistical precision, the multiplicity approach, or detailed missing-data methods. The posted data therefore support a description of the study and its recorded safety information, not a conclusion about which regimen had a greater immune response or a preferable safety profile.

13. Why This Trial Matters Statistically

The trial is statistically informative as an example of how a clinical question can be framed around a threshold-based immune outcome. It specifies four antibody categories, their measurement methods, and the seroprotection cutoffs, alongside a clear assessment time: 1 month after the third vaccination. These elements make the intended endpoint interpretable even though the group results are absent.

The design also highlights the distinction between a randomized comparison and the population actually used for an endpoint analysis. Randomization applies at assignment, while the primary endpoint was assessed in a per-protocol subset available for assessment. Understanding how that subset was formed is important when interpreting any group comparison. Its size and selection details are not reported in the registry record.

Multiplicity matters because the primary outcome involves several antibody categories. A sound interpretation would need to distinguish category-specific estimates from any overall claim and understand whether the analysis controlled or organized multiple comparisons. The record does not report that plan, and it does not provide results that could be checked against one.

Finally, the safety counts show why descriptive data and comparative inference should not be conflated. Counts and listed terms can support a factual account of recorded events, while a comparative conclusion requires clear definitions, an analysis method, and a measure of uncertainty. The record’s main statistical lesson is therefore about the information needed for interpretation: endpoint definitions and design details are useful, but they do not replace reported estimates and their precision.

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 efficacy or immunogenicity is that primary endpoint results are not reported in the registry record. There are no group-specific seroprotection counts, effect estimates, confidence intervals, or p-values. Although the record states thresholds and assays for each antibody category, it is not possible to judge the magnitude or precision of a group difference.

The endpoint is assessed in a per-protocol subset available for the endpoint, but the record does not report the subset size, exclusions, reasons for unavailable measurements, or missing-data handling. Those omissions limit assessment of selection and potential bias. The registry also notes several categories or time points without reducing the primary outcome to one comparison, while the multiplicity strategy is not reported.

Details needed to evaluate the statistical plan are also absent. The registry record does not report the method for comparing binary seroprotection outcomes, the protocol’s sample-size justification, adjustment variables, or whether interim analyses were conducted. The general sample-size illustration is not a substitute for the trial’s own design justification.

Safety interpretation is limited by the lack of a reported comparative analysis and uncertainty estimates. The record does not report the calculation basis for the percentages attached to serious-event terms, or detailed event definitions and ascertainment methods. Death counts are not reported in the registry record. These limitations constrain interpretation of both the immune-response question and the safety summaries; they do not show that a particular bias or problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Comparing a DTaP-HB-PRP~T Combined Vaccine With Tritanrix HepB/Hib™, Concomitantly With OPV in Healthy Infants — NCT00348881.
• Registry record last updated 2013-10-22; status last verified 2013-08.
• Results first posted 2013-10-22.
• 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

NCT00348881 is a completed, randomized, quadruple-masked, parallel-group phase 3 study in healthy Filipino infants, with an enrollment of 2133. It compared DTaP-Hep B-PRP-T combined vaccine with Tritanrix-HepB/Hib™, with both regimens given concomitantly with OPV at 6, 10, and 14 weeks of age.

The primary endpoint counted participants meeting seroprotection thresholds for anti-Hep Bs, anti-PRP, anti-tetanus, and anti-diphtheria antibodies 1 month after the third vaccination. It was assessed in a per-protocol subset available for the endpoint. The registry record does not report primary endpoint group results or a statistical comparison. It lists serious and other adverse-event counts by group and selected serious-event terms, but does not report a comparative safety analysis or death counts.