Safety and Immunogenicity of GSK's Tdap Vaccine (Boostrix) in Adults Aged 19 to 64 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of GSK's Tdap Vaccine (Boostrix) in Adults Aged 19 to 64 Years (NCT00346073), a randomized phase 3 study. The primary outcome is Number of Seroprotected Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.

2. Clinical Question

The question is about antibody response after booster vaccination, not about a clinical illness outcome. The primary measure combines protection thresholds for two diseases: a participant must meet the stated antibody criterion for both diphtheria and tetanus to count as seroprotected. The comparison is between the two vaccine groups in adults aged 19 to 64 years.

The registry describes a randomized trial and identifies Boostrix and Adacel as the study interventions. It reports an enrolled population of 2337. The primary immunogenicity population was narrower than all enrolled participants because it included evaluable participants who met the protocol criteria and had available immunogenicity measures. The number analyzed in that population is not reported in the registry record.

The registry record does not provide one primary-outcome comparison that can be interpreted as the comparative answer to this question. It identifies the endpoint and its Month 1 timeframe, but the primary outcome has several categories or time points and was not reduced to one comparison. No single group contrast, uncertainty interval, or significance test for the primary endpoint is reported in the registry record.

3. Trial Design

This was a Phase 3, randomized, single-masked, parallel-group trial sponsored by GlaxoSmithKline. The study enrolled 2337 participants and is recorded as completed. Its stated purpose was to evaluate the immunogenicity and safety of Boostrix compared with Adacel when given as booster vaccination to adults aged 19 to 64 years.

Participants were assigned to one of two vaccine groups. The Boostrix group received one dose intramuscularly in the deltoid region of the non-dominant upper arm at Day 0. The Adacel group received one dose by the same route and at the same site at Day 0. The allocation is described as randomized, the model as parallel, and masking as single. Who was masked and the specific procedures used to generate and conceal the allocation are not reported in the registry record.

The recorded study start was 2006-07-13, and primary completion was 2007-03-01. The trial addressed acellular pertussis, diphtheria, and tetanus. The primary immunogenicity endpoint was assessed at Month 1, while the registry also lists secondary measures covering antibody concentrations and responses, solicited symptoms, unsolicited adverse events, and serious adverse events. The timing for each secondary measure is not reported in the registry record in the information available for this analysis.

Enrollment is not the same as the number included in every analysis. For the primary immunogenicity analysis, the registry names the According-To-Protocol cohort, consisting of evaluable participants who met eligibility requirements, complied with protocol requirements, and had immunogenicity data available. The number in that cohort is not reported in the registry record. The safety figures use their own reported at-risk group totals; the registry record does not explain how those analysis populations relate to the overall enrollment.

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 2337 subjects were enrolled into the study. Of these, 53 subjects were allocated subject numbers, but did not receive study vaccination.

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 (ATP) cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available.

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 Seroprotected Subjects With Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibodies, measured over At Month 1.

The primary endpoint counts participants who meet a combined antibody criterion for diphtheria and tetanus. At Month 1, a participant is classified as seroprotected if anti-D and anti-T antibody concentrations are both at least 0.1 international units per milliliter. The measure is therefore a participant count based on a binary classification: each participant either meets the stated criterion for both antibodies or does not.

This type of endpoint is used to describe an immune response after vaccination. It translates measured antibody concentrations into a threshold-based status, making the result interpretable as the number of participants reaching the stated seroprotection definition. It is not itself a count of infections, symptoms, or other clinical events.

The combined definition matters. A participant with a qualifying concentration for only one of the two antibodies would not satisfy the endpoint as described, because the definition requires both anti-D and anti-T concentrations to meet the threshold. The registry also lists antibody concentrations and other antibody-response measures among secondary outcomes, but the primary endpoint is the combined seroprotection count at Month 1.

The registry identifies the endpoint, timeframe, and analysis population, but it does not report one primary comparison of the groups. It therefore does not establish from the primary endpoint record alone how the groups compare, nor how precisely any difference is estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what the registry describes from what can be concluded from its results. The trial is randomized, so treatment assignment was intended to create comparison groups through chance allocation. Randomization can reduce systematic differences between groups at baseline, on average, but the registry's design label does not show the actual allocation procedure, whether assignment was concealed, or how well baseline characteristics were balanced. Those details are not reported in the registry record.

What does a binary endpoint count?

The primary endpoint is a binary participant status summarized as a count: seroprotected or not seroprotected according to the combined anti-D and anti-T threshold at Month 1. In general, a binary outcome can be summarized by the number meeting the definition and the number assessed. A comparison may then be expressed using a difference in proportions, a ratio of proportions, or another prespecified measure. These summaries answer different questions and have different scales. The registry record does not identify one primary comparison or provide the results needed to interpret such a measure.

A count alone needs its denominator to be meaningful. The enrolled total of 2337 describes trial enrollment, but it is not necessarily the denominator for every endpoint. For the primary outcome, the registry specifies an According-To-Protocol immunogenicity cohort, which includes evaluable participants meeting eligibility and protocol requirements with available measurements. Its size and the group-specific endpoint denominators are not reported in the registry record. The safety entries, by contrast, report their own at-risk totals.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a statistical model and gives a sense of estimate precision. A narrow interval indicates more precision than a wide interval, while an interval spanning values that point in different directions can leave the comparative result uncertain. A p-value addresses how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and its assumptions. Neither quantity measures clinical importance, and neither substitutes for a clearly defined endpoint and comparison.

No confidence interval or p-value for a single primary endpoint comparison is reported in the registry record. The primary endpoint was not reduced to one comparison in the posted information. Thus there is no basis in the registry record for describing the primary comparative estimate as precise, imprecise, statistically significant, or not statistically significant.

What can planning calculations tell readers?

The stated sample-size assumptions describe planning illustrations based on an observed effect, not the trial's original design justification. The illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the described convention is a total number of events; for other outcomes, it is participants per arm. These assumptions explain the general setup of a planning exercise, not a result of the trial or evidence that the trial had a particular probability of detecting an effect.

Such calculations are prospective illustrations: they show the sample size implied by chosen assumptions and a target effect. They are not observed power, and they do not show whether the trial achieved a result. The registry record does not report the original sample-size justification or the planning assumptions used when the trial was designed. Since the primary comparison is not reported as one estimate, the observed effect underlying any planning illustration is not specified in the registry record.

Why does the analysis population matter?

An According-To-Protocol population focuses on participants who met stated eligibility and protocol requirements and had the required immunogenicity measurements. This can be useful when the question concerns responses among evaluable participants who followed the protocol. It can also differ from an analysis of all randomized participants. Excluding participants after randomization may affect how well the original randomized comparison is preserved, particularly if exclusions are related to treatment or outcome. The registry describes the cohort definition but does not report the size, exclusions, or reasons for exclusion, and it does not state whether an intention-to-treat analysis was also performed.

General statistical interpretation also depends on multiplicity: when many endpoints, groups, or time points are tested, the chance of at least one false-positive finding can increase if no adjustment or prioritization is used. The registry lists 15 outcome measures and 6 analyses, but the multiplicity strategy and inferential hierarchy are not reported in the registry record. It is therefore not possible to determine whether or how multiplicity was addressed for the trial's analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 6 analyses. Several outcome families are represented, including antibody status and concentrations, booster responses, solicited symptoms, unsolicited adverse events, and serious adverse events. When studies examine multiple outcomes or time points, general statistical practice distinguishes a prespecified primary analysis from secondary or exploratory analyses. Without a stated testing hierarchy or multiplicity adjustment, readers cannot know how the chance of false-positive findings across a family of tests was handled. The strategy is not reported in the registry record.

The primary outcome is described as having several categories or time points and is not reduced to one comparison. The registry therefore does not provide a unique primary estimate or inferential test to interpret. The methods for handling missing endpoint data, including any imputation, are not reported in the registry record. The group-specific numbers assessed for the primary endpoint and the reasons for missing measurements are also not reported.

The primary immunogenicity analysis used the According-To-Protocol cohort. The registry defines this as evaluable participants meeting eligibility criteria, complying with protocol requirements, and having immunogenicity measures available. The cohort size, participant flow into it, and exclusions from it are not reported in the registry record. Whether additional analysis populations were used, including an intention-to-treat population, is not reported in the registry record.

These omissions matter because analysis populations and missing-data decisions can affect the number of participants contributing to an estimate and the interpretation of a randomized comparison. The cohort definition alone does not establish how missing observations were treated or whether conclusions were checked under alternative assumptions. No such procedures or sensitivity analyses are reported in the registry record.

11. Safety Results

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

Deaths

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: dehydration (0.2%), abortion spontaneous (0.1%), menometrorrhagia (0.1%), prostate cancer (0.1%), thermal burn (0.1%).

The registry lists serious adverse events for the two groups using separate at-risk totals. In the Boostrix group, it records 21 serious adverse events among 1522 participants at risk. In the Adacel group, it records 13 among 762 participants at risk. The record lists one death in each group. These are reported counts and denominators, not an adjusted comparison.

Counts need context. The groups have different at-risk totals, so the counts alone should not be read as a direct measure of comparative risk. A formal comparison would require a specified analysis, with its estimate and uncertainty, and consideration of how events were defined, collected, and attributed. Those comparative results and details are not reported in the registry record. The figures do not establish that a vaccine caused or prevented an event.

The record lists Dehydration at 0.2%, and Abortion spontaneous, Menometrorrhagia, Prostate cancer, Thermal burn, and Acute myocardial infarction each at 0.1%, among the leading serious-event terms. These listed terms and percentages do not provide complete event histories, timing, or causal assessments. They should be read as reported safety information, not as evidence that an individual event was related to vaccination. The serious-event counts are also distinct from the separate secondary outcome labels for other adverse events and symptoms.

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

The trial addresses a specific comparative immunogenicity question: whether adults aged 19 to 64 years receiving Boostrix or Adacel met a combined diphtheria and tetanus antibody threshold at Month 1. The registry record gives the endpoint definition and identifies the According-To-Protocol analysis population. It also describes the randomized, single-masked, parallel-group design and the two vaccine regimens.

What the record does not provide is a single primary endpoint comparison. There are no reported group counts for that endpoint in one comparison, no estimate of the difference between groups, and no confidence interval or p-value for such a comparison. As a result, these registry entries cannot establish which group had more participants meeting the combined definition, how large any difference was, or how precisely it was estimated. They also cannot establish that the groups were equivalent.

The safety record reports serious-event counts and deaths, along with a set of serious-event terms and percentages. Such entries can describe what was recorded, but they do not alone establish a treatment-caused effect or a comparative safety conclusion. The registry record does not include the comparative statistical analysis, event attribution, or other detail required for those conclusions. A count of events is not a substitute for a prespecified comparison with uncertainty.

The registry also names numerous secondary outcomes, but outcome labels should not be confused with reported findings. The number of outcome measures and analyses indicates a broad set of planned or recorded measures, but the multiplicity approach and missing-data procedures are not reported. Results from one measure, even if available elsewhere, would not automatically answer every other immunogenicity or safety question.

Accordingly, the record supports a description of trial design, endpoints, and selected safety information. It does not support a definitive comparative conclusion about the primary seroprotection endpoint or a causal safety judgment. Lack of a single reported comparison is a limitation of the record, not evidence of no difference between the vaccines.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it illustrates how a clear endpoint definition can coexist with an incomplete comparative result in a registry record. The primary endpoint has a concrete threshold and timeframe: combined anti-D and anti-T seroprotection at Month 1. Those details explain what was intended to be measured. For a comparative interpretation, however, readers also need the group-specific analysis denominators, the number meeting the criterion, and an estimate of the between-group contrast with its uncertainty. Those primary comparison details are not reported in the registry record.

The trial also highlights the distinction between enrollment and analysis populations. Although enrollment is 2337, the primary analysis is described as using an According-To-Protocol cohort of evaluable participants with available immunogenicity measurements. The size of that cohort and the participant flow into it are not reported. Understanding who contributes to an analysis is essential when interpreting whether a randomized comparison has been maintained.

Safety data present a related lesson. Serious-event counts should be interpreted alongside denominators and with attention to uncertainty, event definitions, and attribution. The registry reports counts and at-risk totals, but does not report a comparative estimate or the event-level detail needed for causal conclusions. A numerical count can be informative without being sufficient to rank treatments.

Finally, multiple outcomes and analyses make it important to know which comparisons were primary and how multiplicity was addressed. The record lists many measures, but does not report the analysis hierarchy or multiplicity procedure. Taken together, these features show why transparent reporting must include not only endpoints and counts but also populations, analysis methods, missing-data handling, and uncertainty around comparisons.

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 principal limitation for interpreting the primary endpoint is that the registry does not report a single group comparison. It describes combined seroprotection at Month 1 but does not give the group-specific counts, a comparative estimate, or its uncertainty. The number included in the According-To-Protocol immunogenicity cohort is also not reported in the registry record. This prevents a quantitative assessment of the primary endpoint from the registry information.

The analysis population is defined in general terms, but participant flow, reasons for exclusion, and the number of participants with missing immunogenicity measurements are not reported. The registry record does not describe missing-data handling or report sensitivity analyses. These details would help readers assess how analysis exclusions and unavailable measurements might affect interpretation.

The design is recorded as randomized and single-masked, but the identity of the masked parties, allocation generation and concealment procedures, and baseline balance information are not reported in the registry record. The record also does not give the original sample-size justification, so the planning illustrations should not be confused with the trial's own design rationale.

For safety, the registry provides serious-event counts, at-risk totals, deaths, and selected event terms. It does not provide the comparative statistical analysis, event timing, detailed case information, or causality assessments in the information used for this summary. It also does not explain how the reported safety analysis populations relate to total enrollment. The recorded counts therefore allow description but not a causal or fully adjusted comparative conclusion.

The multiplicity strategy across the listed outcomes and analyses is not reported in the registry record. The lack of this information, together with the absence of a single primary comparison, limits the strength of any inferential interpretation based on the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of GSK's Tdap Vaccine (Boostrix) in Adults Aged 19 to 64 Years — NCT00346073.
• Registry record last updated 2018-08-07; status last verified 2018-02.
• Results first posted 2018-08-07.
• 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

NCT00346073 is a completed, randomized, single-masked, parallel-group Phase 3 trial sponsored by GlaxoSmithKline. It enrolled 2337 adults aged 19 to 64 years and compared single-dose Boostrix with single-dose Adacel, each administered intramuscularly in the deltoid region of the non-dominant upper arm at Day 0.

The primary endpoint was the number of participants with anti-D and anti-T concentrations of at least 0.1 international units per milliliter at Month 1. The primary immunogenicity analysis used an According-To-Protocol cohort of evaluable participants who met eligibility and protocol requirements and had immunogenicity measures available. The cohort size and a single primary comparison are not reported in the registry record.

Safety information lists serious adverse events among 1522 participants at risk in the Boostrix group and 762 in the Adacel group, and one death in each group. The record does not report comparative uncertainty or a causal assessment for these safety entries. Multiplicity and missing-data procedures are not reported in the registry record.