US-licensed Combined Vaccine Against Tetanus & Diphtheria, Given With US-licensed Vaccine Against Meningococcal Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for US-licensed Combined Vaccine Against Tetanus & Diphtheria, Given With US-licensed Vaccine Against Meningococcal Disease (NCT00282295), a randomized phase 4 study. The primary outcome is Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.

2. Clinical Question

The clinical question concerns both the timing of vaccination and the antibody response measured after Boostrix. The co-administration schedule places both vaccines at Day 0, whereas the other schedules give them at separate visits. Those schedules do not simply compare receiving vaccines with not receiving them: all three groups were assigned schedules involving both vaccines. The question is therefore about the antibody endpoint under these schedules, alongside the trial’s stated safety and immunogenicity aims.

The registry describes participants as healthy adolescents and identifies the study as randomized, single-masked, and parallel-group. It does not report which parties were masked or the precise randomization procedures. Although the record lists the primary endpoint and its threshold, it does not provide the primary results needed to assess how many participants met that threshold in each group or how the groups compared.

3. Trial Design

This was a randomized, single-masked, parallel-group Phase 4 trial. The registry lists 1344 enrolled participants and describes the study as completed. Its recorded start date is 2006-01-25, and its primary completion date is 2006-08-08. The record does not report which people were masked, how the allocation sequence was generated, or whether allocation was concealed.

Participants were healthy adolescents 11 through 18 years of age. One group received Boostrix and Menactra together at Day 0. Boostrix was administered intramuscularly into the left deltoid region and Menactra into the right deltoid region. A second group received Boostrix at Day 0 and Menactra at Month 1, with both vaccines administered into the left deltoid region. A third group received Menactra at Day 0 followed by Boostrix at Month 1, also with both vaccines administered into the left deltoid region.

The primary endpoint was a count of participants with anti-diphtheria and anti-tetanus antibodies meeting a stated concentration cut-off at Month 1 after Boostrix vaccination. The record also lists secondary outcomes concerning antibody presence, seroprotection, booster responses, and antibody concentrations for diphtheria, tetanus, and pertussis antigens. The stated timeframe and the three different vaccination schedules make the timing of each assessment important; the registry does not provide enough detail to reconstruct every assessment schedule.

Adverse-event group records list 446 participants at risk in the co-administration group, 446 in the Boostrix-then-Menactra group, and 449 in the Menactra-then-Boostrix group. These are the at-risk counts for the recorded safety categories; they should not be treated as a replacement for the enrollment figure or assumed to define the primary immunogenicity population. Details explaining differences among enrollment, analysis, and safety populations 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: Out of 1344 subjects enrolled, only 1341 were vaccinated.

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 cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available and (\&) randomization code not broken who had received at least 1 dose of study vaccine (known administration site) \& had not received a vaccine not specified or forbidden by the protocol.

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 Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies, measured over At Month 1 (post Boostrix vaccination).

The primary endpoint is the number of participants with anti-diphtheria and anti-tetanus antibodies at the stated cut-off. The registry describes the assessment as taking place at Month 1 after Boostrix vaccination and identifies the cut-off as greater than or equal to 1.0 international units per milliliter (IU/mL). In plain terms, the endpoint counts participants whose measured antibody concentrations meet that threshold. It is a binary classification at the participant level: meeting the threshold or not meeting it.

Such a threshold-based endpoint can make an immune response interpretable in relation to a prespecified concentration criterion. It differs from reporting the average antibody concentration, because the count records how many participants cross the cut-off rather than how high concentrations are among those who do. The registry also lists antibody concentrations and other immune-response measures as secondary outcomes, but those measures address different features of the response.

The record does not report the number meeting the threshold in any group, the denominator used for the primary analysis, or a comparative estimate with a confidence interval. It therefore does not allow a reader to quantify the observed primary response or its precision. The record’s description of the analysis population is incomplete, and the endpoint timeframe is not sufficient to resolve every timing detail across the different schedules.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods depend on the type of outcome and the question being asked. The primary outcome is a participant count based on whether antibody concentrations meet a stated threshold. General explanation: a binary endpoint classifies each participant into one of two categories, such as meeting or not meeting a criterion. A group count can then describe how many participants fall into the category of interest. To interpret that count as a rate, the analysis denominator and missing-measurement handling must also be clear.

What the endpoint counts

The registry specifies anti-diphtheria and anti-tetanus antibody cut-offs of greater than or equal to 1.0 IU/mL, assessed at Month 1 after Boostrix vaccination. The endpoint title refers to the number of participants with these antibodies. It is not an average antibody concentration, and the count should not be confused with a measure of how far above the cut-off participants’ values were. The record lists antibody concentrations separately among secondary outcomes.

General explanation: a threshold can simplify interpretation by converting a continuous measurement into a classification. That can be useful when the scientific question concerns reaching a particular criterion. However, classification discards information about the exact measured concentration. A complete account normally states how concentrations were measured, how results below or above assay limits were treated, and how missing measurements were handled. Those details are not reported in the registry record.

How to think about comparisons

The trial assigned participants to three parallel schedules: both vaccines at Day 0, Boostrix followed by Menactra, or Menactra followed by Boostrix. A comparison of endpoint counts would describe differences between assigned schedules, provided the outcome definitions, assessment timing, and analysis populations are comparable. The registry does not report the group-specific primary counts or comparative estimates, so no numerical comparison can be interpreted.

General explanation: an effect estimate summarizes the observed contrast between groups, while a confidence interval communicates uncertainty around that estimate. A small or wide interval can indicate limited precision; the interval’s interpretation depends on the statistical model and study design. A p-value, when reported, addresses compatibility of the data with a specified null hypothesis under assumptions. It does not describe the size or clinical importance of an effect. No primary effect estimate, confidence interval, or p-value is reported in the registry record.

Analysis populations and missing measurements

The primary population is described as the according-to-protocol cohort for immunogenicity. The available description says that it included evaluable subjects with immunogenicity data available and whose randomization code had not been broken, and refers to receipt of at least one study vaccine with a known administration site. The description ends before giving a complete definition. Other eligibility conditions, exclusions, and handling of protocol deviations are not reported in the registry record.

General explanation: an according-to-protocol analysis typically focuses on participants meeting specified study requirements, while an intention-to-treat analysis generally retains participants in their randomized groups. These populations answer related but distinct questions. The registry’s incomplete cohort description does not establish whether an intention-to-treat analysis was performed or what other analysis populations were used. Missing-data methods, including any imputation or sensitivity analyses, are not reported in the registry record.

Multiplicity and planning

The record lists 19 outcome measures and 12 analyses. A large set of outcomes or comparisons can raise multiplicity concerns, because repeated testing can increase the chance of at least one apparently notable result. General explanation: prespecified testing hierarchies, adjusted significance thresholds, or other strategies may be used to manage this issue. Which outcomes were designated confirmatory, whether any adjustment was used, and the planned statistical tests are not reported in the registry record.

The registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This means a single primary contrast cannot be reconstructed from the record. The sample-size illustrations associated with the posted material are planning exercises based on an observed effect and stated assumptions, not observed power. General explanation: planning calculations describe what a design might detect under their assumptions; they do not show the probability that a completed trial detected an effect. The trial’s own sample-size justification and assumptions are not reported in the registry record.

The study is described as randomized, single-masked, and parallel-group, but further details about randomization, masking, stratification, covariate adjustment, interim analyses, or the statistical model are not reported in the registry record. General explanation: randomization can support fair comparisons by balancing prognostic factors in expectation, while appropriate analysis and transparent reporting are needed to assess the actual comparison. The design label alone does not reveal how these methods were implemented.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and 12 analyses. It includes multiple immune-response outcomes, such as antibody presence, seroprotection, booster responses, and antibody concentrations for several antigens. The primary endpoint itself is described as involving several categories or time points, and the registry record notes that it was not reduced to one comparison. These features make it important to know which outcomes and comparisons were prespecified as primary or confirmatory.

The registry does not report the complete statistical analysis plan, the hierarchy among outcomes, or any method used to address multiplicity. It is therefore not possible to tell whether reported tests, if any, would have been adjusted for multiple comparisons. General explanation: when many hypotheses are tested, a nominal result can be harder to interpret unless the analysis plan addresses the testing structure. The number of listed outcomes alone does not establish that a particular adjustment was required or performed.

The primary analysis population is identified as the according-to-protocol cohort for immunogenicity, but the registry’s description is incomplete. The number included in that cohort and the complete inclusion and exclusion rules are not reported in the registry record. The registry also does not report missing-data methods, imputation, sensitivity analyses, or whether an intention-to-treat analysis was conducted.

These omissions matter because a participant count needs a clear denominator and a defined approach to unavailable measurements. Without the primary counts, analysis denominator, and missing-data handling, the endpoint cannot be independently interpreted from the registry information. The registry’s planning information does not replace these observed-result and analysis details.

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% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: extradural hematoma (0.2%), facial bones fracture (0.2%), leukemia (0.2%).

The registry lists serious adverse events among participants at risk in each group. The recorded serious-event counts are one in the Boostrix + Menactra Group, zero in the Boostrix-Menactra Group, and one in the Menactra-Boostrix Group. Death counts are not reported in the registry record. The entries describe counts within the recorded safety groups; they do not establish whether an event was caused by a vaccine or whether the groups differed in risk.

The registry lists Extradural hematoma, Facial bones fracture, and Leukemia among the top serious-event terms, each at 0.2%. The record does not specify which group or groups these terms correspond to, so they should not be assigned to an individual schedule. The other-event counts are 371, 385, and 358, respectively, in the three groups. The registry does not provide enough detail in these entries to interpret the event definitions, severity composition, or attribution.

General explanation: adverse-event counts are descriptive unless accompanied by a defined comparison, appropriate denominators and follow-up, and context about how events were collected and classified. Serious events can also be uncommon, so counts alone may be imprecise. These registry entries should be read as recorded safety information, not as proof of causation or evidence that one schedule is safer than another.

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

The trial record describes a randomized comparison of three vaccine schedules in healthy adolescents and identifies an antibody-count primary endpoint. It also records safety counts and lists additional immune-response outcomes. These details show what the study set out to examine and how the vaccination schedules differed. They do not, by themselves, show the results of the primary comparison.

The primary outcome results are not reported in the registry record. There are no group-specific primary counts or comparative estimates available in the record, and no primary confidence interval or p-value is reported. As a result, the registry information does not establish the magnitude or precision of any difference in the proportion meeting the antibody cut-off. It cannot support a conclusion about whether schedules were similar or different on this endpoint.

The secondary outcome titles indicate that the study assessed several aspects of antibody response, but their results are not included in the registry information. Listing an outcome is not the same as reporting its findings. Similarly, the presence of safety counts does not establish causal attribution or a reliable comparative safety effect; the registry does not report enough detail for that interpretation.

General explanation: a trial’s design and outcome definitions describe the planned question, while outcome estimates and uncertainty describe what the observed data can support. Interpretation also depends on analysis populations, missing-data methods, and the prespecified handling of multiple outcomes. Those details are incomplete or not reported in the registry record. The findings should therefore not be inferred from the study title, the randomized design, or the fact that the trial is listed as completed.

13. Why This Trial Matters Statistically

This trial addresses a design question that is statistically distinct from a simple treatment-versus-control comparison. All three groups received both vaccines, but the timing differed: one schedule administered them together, while the other schedules administered them in opposite sequences. The statistical contrast is therefore about vaccination schedules and their measured outcomes, not about receiving a vaccine versus receiving none.

The primary outcome is also specific: it counts participants meeting a threshold for anti-diphtheria and anti-tetanus antibodies at a stated time after Boostrix vaccination. Threshold-based counts and continuous antibody concentrations capture different information. The registry lists both kinds of outcomes, which highlights the importance of defining the endpoint before interpreting a comparison. The primary results themselves are not reported in the registry record.

The record also illustrates why population definitions and timing matter. The stated immunogenicity population is an according-to-protocol cohort, but the full definition is incomplete. The sequential schedules place Boostrix at different points, while the primary timeframe is described relative to Boostrix vaccination. Without complete assessment and analysis details, a reader cannot fully reconstruct the comparison.

Finally, the record lists multiple outcomes and analyses but does not report the statistical plan or multiplicity strategy. General explanation: when a trial has several endpoints or time points, the planned testing structure affects how evidence should be interpreted. The design information is useful for understanding the intended question, but the missing outcome estimates and analysis details limit what can be concluded from this record.

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 central limitation of the registry information is that the primary outcome results are not reported in the registry record. Group-specific counts, denominators, comparative estimates, confidence intervals, and primary significance-test results are unavailable. Without those items, the primary endpoint cannot be quantitatively interpreted.

The primary analysis population is described as an according-to-protocol immunogenicity cohort, but the definition is truncated. Its final inclusion and exclusion rules and the number of participants analyzed are not reported in the registry record. The full handling of missing antibody measurements and protocol deviations is also not reported. This prevents a reader from assessing how closely the analyzed participants correspond to those randomized.

The three vaccination schedules differ in timing, and the endpoint timeframe is described as Month 1 after Boostrix vaccination. The registry does not give sufficient detail to reconstruct every assessment visit or confirm exactly how outcomes were aligned across schedules. It also does not report the complete statistical analysis plan, sample-size justification, randomization procedure, allocation concealment, masking details, interim analyses, or any method for managing multiplicity.

Safety information is limited to counts and selected serious-event terms. The registry does not specify the group assignment of the listed serious-event terms, causal attribution, or enough detail about event collection and follow-up to support comparative risk interpretation. Death counts are not reported in the registry record. These limitations concern the registry record’s detail; they do not establish that the information was absent from other trial documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: US-licensed Combined Vaccine Against Tetanus & Diphtheria, Given With US-licensed Vaccine Against Meningococcal Disease — NCT00282295.
• Registry record last updated 2018-08-17; status last verified 2018-06.
• Results first posted 2017-03-16.
• 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 4 trial, NCT00282295, evaluated co-administration of Boostrix and Menactra against two schedules in which the vaccines were given separately to healthy adolescents 11 through 18 years of age. The study was randomized, single-masked, and parallel-group, with enrollment of 1344 participants. The registry lists a start date of 2006-01-25 and a primary completion date of 2006-08-08.

The primary endpoint was the number of participants with anti-diphtheria and anti-tetanus antibodies meeting the stated cut-off of greater than or equal to 1.0 IU/mL at Month 1 after Boostrix vaccination. Although the endpoint and analysis population are described, the primary outcome results are not reported in the registry record. The record lists secondary immune-response outcomes and safety counts, but provides limited detail for interpreting comparisons, missing data, or multiplicity.