Post-licensure, Modified Double-blind, Multi-center Study Evaluating Safety and Immunogenicity of ADACEL® and BOOSTRIX®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-licensure, Modified Double-blind, Multi-center Study Evaluating Safety and Immunogenicity of ADACEL® and BOOSTRIX® (NCT00319553), a randomized phase 4 study. The primary outcome is Number of Participants Reporting A Solicited Injection Site or Systemic Reactions Within 7 Days Following Vaccination With Adacel® or Boostrix®.

2. Clinical Question

The record frames the study as descriptive and identifies safety and immunogenicity as its focus. The named primary outcome concerns solicited reactions: pain, erythema and swelling at the injection site, and fever, headache, malaise and myalgia as systemic reactions. It also defines grade 3 reactions, but the primary outcome title concerns the number of participants reporting reactions, not an inferential test of a treatment difference.

The central statistical question is therefore descriptive: what reaction counts were recorded in each randomized group, and how completely are those counts reported? A comparison would also require a clear account of the relevant categories, denominators and analysis. The registry record does not report a single reduced comparison for this multi-category endpoint or a statistical analysis result. It does not establish, from the information reported, whether the groups differ in their reaction profiles.

3. Trial Design

The registry record describes a randomized, parallel-group Phase 4 study with quadruple masking. Its title characterizes the study as post-licensure, modified double-blind and multicenter; the record separately lists masking as quadruple. These descriptions are retained as recorded, without inferring who was masked or how masking was implemented. Sanofi is listed as the sponsor. The status is completed, with a start date of 2006-05 and primary completion in 2008-10.

The study compared two active vaccine groups: ADACEL® and BOOSTRIX®. The record gives an enrollment of 647. The arm descriptions are blank, so details beyond the intervention names are not reported in the registry record. The allocation ratio, methods used to generate or conceal the allocation, study sites, eligibility criteria, and participant flow are not reported in the registry record.

The registry record lists Pertussis, Tetanus and Diphtheria as conditions. Its brief summary describes a descriptive evaluation of safety and immunogenicity among US adolescents. The primary endpoint is a solicited-reaction outcome observed during Day 0 to 7 post-vaccination. It lists an intent-to-treat safety population for analysis of these reactions.

Although the record lists four outcome measures, it does not report an inferential analysis for the primary endpoint; the analysis count is 0. The record also does not provide a protocol, a sample-size justification, or a detailed statistical analysis plan. Those omissions prevent a reader from assessing whether the reported outcomes and analyses match a prespecified plan, or how the study intended to handle multiple outcomes, missing observations, and comparisons between groups.

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 647 participants who met the inclusion and exclusion criteria were enrolled, 644 were vaccinated and included in the analysis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Solicited injection site and Systemic reactions were analyzed in the intent-to-treat safety 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 Reporting A Solicited Injection Site or Systemic Reactions Within 7 Days Following Vaccination With Adacel® or Boostrix®, measured over Day 0 to 7 post-vaccination.

The primary endpoint is the number of participants reporting solicited injection-site or systemic reactions during Day 0 to 7 post-vaccination. The listed injection-site reactions are pain, erythema and swelling; the systemic reactions are fever, headache, malaise and myalgia. The record says these reactions were analyzed in the intent-to-treat safety population.

Solicited outcomes use a defined list of symptoms, making the observation target explicit: participants are considered with respect to whether they reported particular reactions during a stated period. This can support a structured description of short-term reactions after vaccination. It does not, by itself, establish how severe, persistent or clinically consequential a reaction was. The endpoint's summary count also does not convey which reactions occurred unless results are separated by category.

The record defines grade 3 reactions as incapacitating pain that prevents usual activities; erythema or swelling measuring at least 5 cm; fever reaching at least 39.1°C or 102.3°F; or headache, malaise or myalgia that prevents daily activities. These definitions clarify the severity threshold, but the primary outcome title is a count of participants reporting solicited reactions overall. Category-specific and grade-specific primary results are not reported in the registry record. The record therefore describes what was to be measured, but does not provide enough outcome detail to characterize the observed reaction pattern or compare the vaccines statistically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization and parallel groups. General: randomization assigns participants to study groups using a chance-based process. Its purpose is to reduce systematic differences between groups at assignment, so that a comparison is less vulnerable to selection effects. This registry record identifies the study as randomized and parallel, with ADACEL® and BOOSTRIX® groups. It does not describe the sequence-generation or allocation-concealment methods, so those procedures cannot be evaluated from the registry record.

General: in a parallel-group design, participants remain assigned to one group for the comparison rather than crossing between interventions. This design makes outcomes in the groups comparable only to the extent that allocation, follow-up, outcome measurement and analysis support that comparison. The record lists an enrollment of 647, but does not provide participant flow or the number contributing to each primary endpoint category.

Masking. The registry record lists quadruple masking, while its title describes the study as modified double-blind. Masking is intended to limit the influence of knowledge of group assignment on participant reports, care or outcome assessment. General: how masking helps depends on who is unaware of assignment and whether that information could affect measurement or conduct. The registry record does not identify the masked roles or explain the difference between the title wording and the masking classification. The masking procedure therefore cannot be assessed in detail.

Descriptive counts and comparisons. The primary outcome is a participant count for solicited reactions. General: counts describe how many participants met an outcome definition; they are not, on their own, a complete comparison. A comparative analysis typically also needs the relevant denominator, a defined contrast between groups, and an estimate of uncertainty. For an outcome with several reaction categories, each category may have a different count and interpretation. The record lists four outcome measures and names multiple reaction types, but does not report category-specific primary results or an inferential analysis. No effect estimate, confidence interval or p-value for the primary endpoint is reported in the registry record.

General: a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while an interval that includes values compatible with no difference does not establish that groups are identical. Since no primary confidence interval is reported, precision for the vaccine comparison cannot be assessed from this record.

Severity definitions. The endpoint includes definitions of grade 3 reactions. They distinguish reactions by functional impact or specified size or temperature thresholds: incapacitating pain; erythema or swelling of at least 5 cm; fever at least 39.1°C or 102.3°F; or symptoms that prevent daily activities. These definitions make the intended severity classification more reproducible. They do not tell the reader how many participants met each definition; those results are not reported in the registry record.

Sample-size planning. General: sample-size calculations are planning tools that depend on assumptions about the effect to detect, variability or event frequency, allocation, significance level and statistical method. The planning illustrations use a two-sided significance level of 0.05, equal allocation and a normal approximation, with the effect expressed as a fraction of the observed effect. They are planning illustrations, not observed power and not evidence of the trial's original design rationale. The registry record does not report the trial's own sample-size justification or the assumptions used by its investigators.

For non-time-to-event outcomes, planning values are expressed as participants per arm for 80% power or other stated planning targets; time-to-event planning values concern total events. General: a planning calculation should not be read as a retrospective measure of how likely the study was to detect a difference after the results were known. The observed effect, its uncertainty and the prespecified analysis are distinct from an illustration calculated for a chosen planning scenario.

Over-dispersion and binary outcomes. General: over-dispersion occurs when outcome variation exceeds what a chosen statistical model expects. If present, it can make standard errors too small and confidence intervals too narrow unless the model accounts for it. The primary endpoint is represented as participant counts, but the record does not report a model, an over-dispersion assessment, or a model-based analysis. It is therefore not possible to say whether such a method was used or warranted in the trial's analysis.

Reported analyses. The registry record lists no analyses. This does not prove that no analyses were conducted outside the registry, but it means that their methods and results cannot be evaluated from the posted record. The analysis population is identified as the intent-to-treat safety population for solicited reactions; further details about inclusion, missing observations, or deviations from the assigned group are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes several solicited reaction categories: pain, erythema, swelling, fever, headache, malaise and myalgia. The registry record also lists four outcome measures. When multiple outcomes or categories are examined, the number of statistical comparisons can affect how often apparently notable findings arise by chance. General: multiplicity procedures can control or describe this issue, but the appropriate approach depends on the prespecified questions and analysis plan.

The record does not report a multiplicity strategy, a hierarchy of outcomes, or an analysis plan specifying which comparisons were confirmatory. Its skip note states that the primary outcome has several categories or time points and was not reduced to one comparison. The analysis count is 0. Consequently, there is no reported inferential result to evaluate for multiplicity, and it is not possible to determine whether any adjustment or prespecified selection procedure was used outside the posted record.

Missing-data handling is not reported in the registry record. The record identifies the intent-to-treat safety population for analysis of solicited reactions, but does not describe how missing symptom reports, incomplete follow-up, withdrawals or participants without evaluable observations were handled. The number of participants contributing to each primary reaction category is also not reported. The record's enrollment figure alone does not establish how many participants were assessed for each outcome.

General: missing observations can affect a comparison when their occurrence or handling is related to group assignment or outcomes. Interpretation depends on the extent and pattern of missingness, the analysis population, and the assumptions made in any statistical method. Because those details are not reported, the completeness and robustness of the primary endpoint analysis cannot be assessed from the registry record.

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 5.0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event summary reports 0 participants affected in the Adacel® Vaccine Group, with 323 at risk, and 0 affected in the Boostrix® Vaccine Group, with 321 at risk. These are the serious-event participant counts recorded for the groups. They do not mean that the underlying risk is known to be zero, and they do not establish equivalence between the vaccines. No confidence interval or comparative analysis of serious events is reported in the registry record.

The record separately lists other adverse events: 273 affected among 320 at risk in the Adacel® group, and 257 affected among 317 at risk in the Boostrix® group. These figures should not be interpreted as a breakdown of particular symptoms or as a measure of severity. The registry record does not give event terms or further definitions for these other events in the posted summary. The death counts are not reported in the registry record; a missing value should not be read as a reported zero.

General: adverse-event counts describe observed participants within the recorded risk sets. A comparison requires attention to event definitions, follow-up, denominators and uncertainty, not just the counts. The registry record does not report enough detail to assess those features or make a statistical comparison of the groups.

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

The registry record establishes that a randomized, parallel-group Phase 4 study compared ADACEL® and BOOSTRIX® in US adolescents, and that the study is listed as completed. It identifies solicited reactions during Day 0 to 7 post-vaccination as the primary endpoint and describes definitions for reaction severity. These details tell readers what the investigators intended to observe, but they do not supply the category-specific primary results.

The posted safety summary records 0 participants affected by serious adverse events in each group, alongside the respective at-risk counts. It also records other adverse-event counts for both groups. These are descriptive data, not proof of equal safety profiles, and the serious-event figures do not establish that serious events cannot occur. The record does not provide the uncertainty estimates or inferential comparison needed to quantify how precisely the groups differ.

The record's descriptive framing matters. Without reported primary outcome counts by reaction category, statistical estimates and a stated analysis, readers cannot judge the size or precision of any comparative difference for solicited reactions. Without reported immunogenicity results, the study's immunogenicity objective cannot be interpreted from this registry record. No conclusion that one vaccine is superior, inferior or equivalent follows from the information posted.

General: a non-significant result, if one were reported, would not by itself establish equivalence; an equivalence conclusion requires an appropriate design, a prespecified margin and an analysis that addresses that question. None of those elements is reported in the registry record. Similarly, planning illustrations are hypothetical calculations for specified assumptions, not observed power and not substitutes for outcome estimates. The most defensible reading is limited to the design and descriptive counts explicitly recorded, while treating unreported results and methods as unknown.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized comparison of two active vaccines in a post-licensure setting, with a stated focus on safety and immunogenicity. Randomization and parallel groups provide a framework for comparing outcomes, while the solicited-reaction endpoint gives a defined set of short-term symptoms to record. The record also specifies functional and threshold-based criteria for grade 3 reactions, which can make severity classifications more consistent when applied as intended.

The statistical value of that framework depends on complete reporting. For an endpoint with multiple reaction categories, readers need to know the counts for each category, the denominators, and how the comparison was analyzed. The registry record does not report those primary results or an inferential analysis. This makes the distinction between a well-described outcome and an interpretable result especially important: endpoint definitions clarify what is measured, but they do not show what was observed.

The serious adverse-event summary illustrates another core statistical point. Zero observed affected participants in each group is a descriptive finding, not evidence that the risks are identical or absent. Precision and comparative interpretation require suitable estimates and uncertainty, neither of which is reported for these serious-event counts.

The record is also a reminder that planning calculations and trial results answer different questions. Sample-size illustrations can show how assumptions relate to a planning target, but they do not document the investigators' original justification or establish observed power. Transparent reporting of protocol, analysis populations, missing-data handling, multiplicity decisions and results is necessary for readers to assess a trial's evidential contribution. Those details are not reported in the registry record, limiting statistical interpretation even though the broad design and outcome definitions are stated.

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 trial-specific reporting gaps limit interpretation. The primary endpoint combines multiple solicited reactions, but category-specific counts and grade-specific results are not reported in the registry record. The record lists four outcome measures but provides no analyses. It therefore does not provide the effect estimates, confidence intervals or p-values needed to assess comparative results or their precision.

Although the study is described as evaluating immunogenicity, immunogenicity outcomes and results are not reported in the registry record. The arm descriptions are blank, and the record does not report participant eligibility criteria, demographic characteristics, allocation methods, study sites, participant flow, or group-specific primary endpoint denominators. The enrollment figure cannot answer those questions.

The registry record does not report the protocol, the study's sample-size justification, the statistical analysis plan, multiplicity procedures, or missing-data methods. It identifies an intent-to-treat safety population for solicited reactions, but does not explain its operational definition or how incomplete reports were handled. The record lists quadruple masking, while the title describes modified double-blinding; who was masked and how the masking was implemented are not reported.

The adverse-event summary includes serious and other event counts, but does not give event terms or a detailed comparative analysis. Death counts are not reported in the registry record. These gaps prevent assessment of event composition, precision and potential differences in follow-up or ascertainment. The posted information supports a limited descriptive account of the study design and selected safety counts, not a comprehensive evaluation of comparative safety or immunogenicity.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Post-licensure, Modified Double-blind, Multi-center Study Evaluating Safety and Immunogenicity of ADACEL® and BOOSTRIX® — NCT00319553.
• Registry record last updated 2012-10-05; status last verified 2012-09.
• Results first posted 2010-10-21.
• 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

NCT00319553 is a completed, randomized, parallel-group Phase 4 study sponsored by Sanofi. It compared ADACEL® and BOOSTRIX® among US adolescents and lists an enrollment of 647. The record identifies quadruple masking; the title describes the study as modified double-blind and multicenter.

The primary endpoint counts participants reporting solicited injection-site or systemic reactions during Day 0 to 7 post-vaccination. The record names the reaction categories and defines grade 3 reactions. It identifies the intent-to-treat safety population for those reactions, but does not report category-specific primary results or an inferential analysis. The registry record lists four outcome measures and 0 analyses.

Serious adverse-event counts are reported as 0 affected among 323 at risk in the Adacel® group and 0 among 321 at risk in the Boostrix® group. Other adverse-event counts are also listed, but detailed event terms and comparative analyses are not reported. Immunogenicity results, the sample-size justification, missing-data methods and multiplicity procedures are not reported in the registry record. The available information supports description of the design and selected counts, but not a precise statistical comparison of the primary endpoint.