A Study of DTaP-IPV-Hep B-PRP-T Vaccine Given With Prevenar™ and Rotarix™ in Healthy Latin American Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of DTaP-IPV-Hep B-PRP-T Vaccine Given With Prevenar™ and Rotarix™ in Healthy Latin American Infants (NCT01177722), a randomized phase 3 study. The primary outcome is Geometric Mean Titers (GMTs) of Anti-Hepatitis B Before and After 3 Dose Primary Vaccination With Either DTaP-IPV-Hep B-PRP~T Batch A, B, or C, or Infanrix Hexa™.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group study. Its stated purpose was to generate immunogenicity and safety data for an investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine compared with Infanrix hexa™, with both given alongside Prevenar™ and Rotarix™. The registry records enrollment of 1375 and a completed study. The listed start was 2010-08 and primary completion was 2011-10.

The study included four groups: investigational vaccine lots A, B and C, and an active-control group. The primary objectives addressed two distinct questions: whether the immunogenicity of the three investigational lots was equivalent, and whether the investigational vaccine was non-inferior to the licensed hexavalent control. The registry also lists secondary aims to describe immunogenicity parameters for all antigens and assess solicited and unsolicited adverse events and serious adverse events.

Random allocation and masking are design features intended to reduce bias in treatment assignment and outcome assessment. In general, a parallel-group design assigns participants to a study group and follows that group, rather than switching participants between treatments. The registry identifies the masking as quadruple but does not specify which roles were masked. It also does not report the allocation ratio, randomization method, or details of any stratification.

The listed primary endpoint population was per protocol, excluding subjects with protocol violations that might interfere with evaluation of the primary criteria. The number included in that population is not reported in the registry record. Although total enrollment is given, arm-specific enrollment for the primary analysis is not reported there. The study’s planned sample-size justification and detailed statistical analysis plan are also 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 1375 participants who met all inclusion criteria and none of the 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: GMTs were assessed in all subjects who did not have any protocol violation that might interfere 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 Geometric Mean Titers (GMTs) of Anti-Hepatitis B Before and After 3 Dose Primary Vaccination With Either DTaP-IPV-Hep B-PRP~T Batch A, B, or C, or Infanrix Hexa™, measured over Day 0 (pre-vaccination) Dose 1 and 30 days post-vaccination.

The primary endpoint is the geometric mean titer (GMT) of antibodies against hepatitis B. Antibodies were measured using chemiluminescence detection. The stated time points are Day 0 before dose 1 and 30 days post-vaccination, following a 3-dose primary vaccination series. The outcome is assessed in the Per-Protocol Population, defined in the record as subjects without protocol violations that might interfere with evaluation of the primary criteria.

A geometric mean summarizes antibody measurements on a multiplicative scale. In general, this measure is used when values are positive and their distribution is more naturally considered in terms of proportional rather than additive changes. It provides a group-level summary, not an account of every participant’s response. The registry lists a 95% confidence interval for the GMT, which expresses uncertainty around the estimated group value; it does not show the range of individual antibody measurements.

GMTs are relevant to immunogenicity questions because they summarize antibody response after vaccination. The trial’s objectives concern whether the investigational lots have equivalent immunogenicity and whether the investigational vaccine is non-inferior to the active control. However, the registry record does not report the GMT estimates, confidence interval limits, or numerical comparison results. The endpoint definition alone therefore does not establish whether either objective was met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record names geometric mean titers and a 95% confidence interval as the primary endpoint summary. It does not provide numerical GMTs or confidence limits, so interpretation is limited to explaining what these methods mean in general and what information is missing for evaluating the stated objectives.

What does a geometric mean summarize?

In general, a geometric mean is calculated on a logarithmic scale and then expressed on the original measurement scale. This approach is appropriate for positive measurements when proportional changes are more meaningful than fixed additive changes. A GMT gives a central group summary; it does not indicate that all participants had the same response, nor does it describe the spread of individual values by itself.

The endpoint concerns antibodies against hepatitis B measured by chemiluminescence detection. The specified time points are Day 0 before dose 1 and 30 days post-vaccination. Comparing measurements at different times can describe the pattern of antibody response, but the record does not provide the numerical values or a calculated change between those time points. No change should be inferred from the endpoint label alone.

How should a confidence interval be read?

In general, a confidence interval represents uncertainty in an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. A 95% confidence interval is a method-based interval, not a statement that a particular participant’s value has a 95% probability of lying within it. The actual confidence interval limits for the primary GMT are not reported in the registry record.

For a comparison between groups, the interval around the contrast is important because it shows the range of values compatible with the observed data under the analysis. The record does not report a contrast, its confidence interval, or a p-value for the primary endpoint. It therefore does not permit an assessment of the precision or direction of the group comparisons.

What is special about equivalence and non-inferiority?

In general, equivalence asks whether the difference between treatments is sufficiently small in either direction, according to a prespecified equivalence margin. Non-inferiority asks whether the investigational treatment is not worse than the comparator by more than a prespecified margin. These are not the same as ordinary tests that look only for evidence of a difference. Their interpretation depends on the chosen margin, the direction of the comparison, the analysis population, and the confidence interval for the treatment contrast.

The registry states that equivalence among lots and non-inferiority versus Infanrix hexa™ were primary objectives. It does not report the margins or the numerical analyses needed to evaluate them. The record also does not report the planned statistical test or a rationale for the margins. The objectives therefore describe intended questions, not conclusions.

What does the per-protocol population imply?

The primary endpoint was assessed in subjects without protocol violations that might interfere with primary-criteria evaluation. In general, a per-protocol analysis focuses on participants who adhered sufficiently to the study requirements. It can answer a question about outcomes under protocol adherence, but it can be affected by exclusions after randomization. Comparing it with an analysis that retains participants according to randomized assignment can help identify whether conclusions are sensitive to those exclusions.

The number in the Per-Protocol Population, the reasons for any exclusions, and any additional analysis populations are not reported in the registry record. Nor does the record describe how missing antibody measurements were handled. Without these details, the effect of exclusions or missing data on the endpoint cannot be assessed.

What can the planning illustration establish?

Planning sample sizes are not observed treatment results and are not a measure of the study’s observed power. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The stated illustration distinguishes participants per arm for 80% power and participants per arm for 90% power; time-to-event calculations, if present, use total events. Such calculations are planning illustrations, not evidence that a treatment effect exists. Numerical planning results and the trial’s own design justification are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study has multiple intended comparisons and outcomes. The primary objectives address equivalence among three investigational lots and non-inferiority versus the active control. The record also lists secondary immunogenicity outcomes and safety outcomes, including solicited and unsolicited adverse events and serious adverse events. Multiple comparisons can increase the chance of a misleading finding if they are interpreted without an appropriate plan for controlling or contextualizing multiplicity.

The registry record does not report whether or how multiplicity was addressed. It does not describe a hierarchy of hypotheses, adjustment procedure, or which comparisons would be considered confirmatory. Because the primary endpoint title refers to GMTs before and after vaccination and the record identifies several groups, the intended comparison structure requires more detail than the outcome label alone provides. The record notes that the primary outcome has several categories or time points and is not reduced to one comparison.

Missing-data handling is also not reported in the registry record. The record does not state how unavailable antibody measurements, withdrawals, or other missing observations were treated. It also does not give reasons for missingness or numbers with measurements at each time point. This matters because the primary population is per protocol, and exclusions or incomplete observations can affect which participants contribute to the endpoint analysis.

The number analyzed for each outcome, the definition of any analysis populations beyond the Per-Protocol Population, and any sensitivity analyses are not reported in the registry record. Without these details and the numerical results, it is not possible to determine whether the stated conclusions would be robust to alternative analysis choices.

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 (3.2%), bronchiolitis (2.6%), urinary tract infection (0.9%), convulsion (0.6%), febrile convulsion (0.6%).

The registry lists serious adverse-event counts by group. For investigational lot A, 10 participants with serious adverse events are listed among 345 at risk; for lot B, 14 among 343; for lot C, 16 among 342; and for Infanrix Hexa, 10 among 345. These are group-specific registry counts and should be read as counts, not as proof that a vaccine caused an event. The record does not provide a causal assessment for these events.

Other adverse events are also listed by group: 208 among 345 for lot A, 206 among 343 for lot B, 216 among 342 for lot C, and 193 among 345 for Infanrix Hexa. These counts are distinct from the serious adverse-event counts in the record. The registry does not provide enough detail in these summaries to establish event severity, timing, duration, or relationship to vaccination for each participant.

The serious-event terms listed include Pneumonia at 3.2%, Bronchiolitis at 2.6%, Urinary Tract Infection at 0.9%, Convulsion at 0.6%, Febrile Convulsion at 0.6%, and Cardiac Failure at 0.3%. The registry record does not identify the denominator or group-specific context for these term percentages. Death counts are not reported in the registry record.

In general, adverse-event counts are descriptive safety information. Comparisons require attention to denominators, follow-up, event definitions, and attribution; the counts alone do not establish causation or a comparative safety effect.

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

The study’s stated aim was to assess immunogenicity and safety for an investigational hexavalent vaccine given with Prevenar™ and Rotarix™, compared with Infanrix hexa™ given in the same context. It also set out to compare immunogenicity among three investigational lots. These are the questions the trial was designed to address, not findings that can be confirmed from the registry record’s numerical results.

The primary endpoint is a biologically relevant antibody measure: anti-hepatitis B GMTs at Day 0 and 30 days post-vaccination. In general, antibody measurements can describe an immune response, but a GMT is a group summary and does not show the full range of individual responses. The record does not provide the GMT estimates or their confidence intervals, so neither the size nor the precision of the antibody response can be described.

Equivalence and non-inferiority require analysis against prespecified margins. The registry lists these objectives but does not report their margins, comparison estimates, or analysis results. Thus, the objectives cannot be treated as proof that the lots were equivalent or that the investigational vaccine met the non-inferiority objective.

The record includes adverse-event counts and selected serious-event terms, but these are descriptive entries. They do not by themselves establish whether an event was caused by vaccination or whether groups differ meaningfully in safety. Context such as timing, attribution, and analysis details is not reported in the registry record.

Accordingly, the record can inform readers about the planned design, endpoint, analysis population, and selected safety summaries. It cannot establish the primary immunogenicity findings, the precision of any group comparison, or whether either primary objective was met. Those conclusions require numerical results and the corresponding statistical analyses, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a set of statistical questions common to vaccine studies. It compares three lots of an investigational vaccine with an active control while also describing immune responses and safety. Separating lot consistency from a comparison with the control is important: equivalence among lots and non-inferiority versus a control are different hypotheses and need their own definitions and analyses.

The endpoint is a geometric mean titer, a group-level summary suited in general to positive antibody measurements that may be interpreted proportionally. Reporting a confidence interval alongside a GMT is useful because an estimate without its uncertainty can give an incomplete picture. In this registry record, the endpoint and interval type are identified, but the estimates and interval limits are not reported.

The stated Per-Protocol Population makes the analysis population part of the interpretation. In general, a per-protocol result depends on how protocol violations are defined and which participants are excluded. Transparent reporting of exclusions, missing measurements, and complementary analysis populations helps readers understand whether the result reflects the randomized groups or a selected subset.

Finally, multiplicity matters because the study includes several primary objectives, vaccine groups, time points, and secondary outcomes. The registry record does not report how these multiple questions were handled statistically. That omission, alongside the absence of numerical primary results, prevents an assessment of the strength and precision of the intended comparisons. The record is informative about study structure but does not supply the evidence needed to judge its primary statistical claims.

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.

A central limitation of the registry record is the absence of numerical primary endpoint results. It identifies anti-hepatitis B GMTs and a 95% confidence interval but does not report the group estimates, interval limits, or formal comparisons. It therefore does not allow assessment of the magnitude or precision of the immunogenicity findings.

The record states equivalence and non-inferiority objectives but does not report the corresponding margins or detailed analysis plan. Without these, the criteria for interpreting those objectives are unclear. The record also does not report whether multiplicity was addressed across the lot comparisons, active-control comparison, time points, and secondary outcomes.

The Per-Protocol Population is described, but its size, the number excluded, and the reasons for exclusion are not reported in the registry record. The number of participants with endpoint measurements at each time point and the handling of missing data are also not reported. The total enrollment figure does not substitute for these analysis details.

For safety, the record includes group counts and selected serious-event terms, but does not provide event timing, individual attribution, or the context for the listed term percentages. It does not report deaths. The data presented do not support a causal interpretation or a definitive comparison of safety between groups.

Finally, the planned sample-size justification and detailed statistical analysis plan are not reported in the registry record. The planning illustration is not a substitute for the trial’s own rationale or for observed results. These omissions limit the conclusions that can be drawn from the registry information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of DTaP-IPV-Hep B-PRP-T Vaccine Given With Prevenar™ and Rotarix™ in Healthy Latin American Infants — NCT01177722.
• Registry record last updated 2014-05-05; status last verified 2014-04.
• Results first posted 2014-05-05.
• 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 Phase 3 study was randomized, quadruple-masked, and parallel-group, with enrollment of 1375. It evaluated three lots of DTaP-IPV-Hep B-PRP-T against an active control identified as Infanrix hexa™, with Prevenar™ and Rotarix™ given concomitantly. The listed primary objectives were equivalence among the investigational lots and non-inferiority versus the control.

The primary endpoint was anti-hepatitis B geometric mean titers measured by chemiluminescence detection at Day 0 before dose 1 and 30 days post-vaccination. Assessment was specified for the Per-Protocol Population. The registry record includes selected adverse-event counts and serious-event terms but does not report numerical primary endpoint results, formal analyses, multiplicity handling, or missing-data methods. Accordingly, the intended primary comparisons cannot be evaluated from the registry record.