Post-marketing Evaluation of Reactions Following Receipt of Recommended Adolescent Pertussis Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-marketing Evaluation of Reactions Following Receipt of Recommended Adolescent Pertussis Vaccine (NCT00304265), a randomized phase 4 study. The primary outcome is Number of Participants Reporting a Solicited Local or Systemic Reaction Post-Vaccination With Either REPEVAX® or COVAXIS® Vaccine.

2. Clinical Question

3. Trial Design

This was a completed phase 4, randomized, parallel-group trial with no masking. The registry records enrollment of 215 participants. The study was designed as a post-marketing evaluation of reactions following adolescent pertussis vaccination, with the comparison organized around prior pertussis-vaccine history.

The 6th Dose Pertussis Vaccine Group is described as participants receiving a 6th dose of pertussis vaccine. The 5th Dose Pertussis Vaccine Group is described as participants receiving a 5th dose. In the study summary, the former group comprises adolescents 10-14 years of age who participated in study 371-03/01 and thus received a 5th dose of TRIPEDIA®. The control group is described as adolescents 10-14 years of age with at least three doses of whole-cell pertussis vaccine in infancy and at least one subsequent pertussis-vaccine dose in their 2nd through 7th year of life.

The intervention listing names COVAXIS™ and REPEVAX®. The summary describes REPEVAX® as Tdap-IPV and COVAXIS® as Tdap. The registry record does not report how participants were allocated between the two vaccine products, or whether product choice was randomized. It records randomized allocation for the trial, but allocation concealment and the allocation ratio are not reported in the registry record. Masking was none.

The trial started in 2006-03, had primary completion in 2006-10, and is marked completed. These design details establish the setting for interpreting the reported safety counts, but do not by themselves establish how completely reactions were captured or whether the groups were comparable in characteristics beyond their described vaccine histories.

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 214 participants who met the inclusion and exclusion criteria were enrolled and vaccinated. One over aged participant was also vaccinated and included in the safety analysis.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat 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 Local or Systemic Reaction Post-Vaccination With Either REPEVAX® or COVAXIS® Vaccine, measured over Days 0 to 14 Post-vaccination.

The primary endpoint is the number of participants reporting a solicited local or systemic reaction after vaccination with REPEVAX® or COVAXIS®. The observation window was Days 0 to 14 Post-vaccination. The solicited local reactions were pain, erythema, swelling, and arm circumference; solicited systemic reactions were fever (temperature), headache, malaise, and myalgia.

Solicited outcomes use a specified list of symptoms or findings. In general, this can make safety monitoring more systematic than relying only on spontaneous reports: participants and study staff know which reactions are being sought, and the same categories can be assessed across groups. These measures describe reported reactions during the defined observation window. They do not, by themselves, establish that vaccination caused a reaction, because symptoms may occur for other reasons and the registry record does not report a causal attribution method.

The registered endpoint is a count of participants, not a severity score or a time-to-event measure. However, the outcome has multiple reaction categories and a defined period of follow-up. The registry notes that it was not reduced to one comparison. Consequently, no single group contrast, effect estimate, confidence interval, or significance test for this primary endpoint is reported in the registry record. The adverse-event counts listed separately should not be treated as a substitute for a category-specific result for the solicited endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomized allocation is intended, in general, to reduce systematic differences between groups at enrollment by assigning participants through a chance-based process. Here, the registry labels allocation as randomized, but the described groups are also defined by prior pertussis-vaccine histories. The registry does not report allocation concealment, the allocation ratio, or details of the randomization procedure. The design label alone does not show how closely the groups were balanced in this trial.

What does a parallel-group design mean?

In a parallel design, participants are assigned to groups and followed within their assigned group rather than receiving a sequence of study interventions. The record identifies a parallel model and the 6th Dose and 5th Dose Pertussis Vaccine Groups. This structure supports descriptive group-specific reporting. It does not, on its own, establish that an observed group difference is caused by the difference in prior vaccine history or by the adolescent vaccine product.

What does “no masking” imply?

The registry records masking as none. In general, masking can reduce the influence of knowledge about treatment assignment on reporting, assessment, or interpretation. When participants and assessors know which group a participant is in, subjective reports may be more susceptible to expectations. This is relevant to solicited reactions, which depend in part on participant reporting. The record does not provide further detail about who collected the reaction information or how assessments were standardized.

How should counts be understood?

The adverse-event entries report participants at risk and participants with events. Such counts are descriptive; they do not quantify uncertainty or make a statistical adjustment for differences between groups. A comparison would ordinarily need a clearly defined outcome, a stated analysis population, and a method for estimating the group contrast and its uncertainty. Those inferential results are not reported in the registry record. The count entries for “other” events should also be kept distinct from the solicited primary endpoint, whose multiple categories were not reduced to a single comparison.

What would a confidence interval add?

In general, a confidence interval expresses the precision of an estimated effect under a specified statistical model. A narrow interval indicates greater precision than a wide interval, while an interval spanning values compatible with different conclusions leaves more uncertainty about the size and direction of an effect. No confidence interval for the primary group comparison is reported in the registry record, so the precision of a comparative effect cannot be assessed from the posted material.

Why can event counts be difficult to compare?

Counts depend on the number of participants with available outcome data and on how outcomes were collected. A count without a clearly defined denominator or a compatible follow-up population may not support a fair comparison. For the other-event entries, the registry reports 117 at risk and 89 affected in the 6th Dose Pertussis Vaccine Group, and 97 at risk and 87 affected in the 5th Dose Pertussis Vaccine Group. The record does not report an inferential comparison for these entries. No derived rate or contrast is stated.

For outcomes that are more variable than a basic statistical model assumes, over-dispersion can make standard errors too small and confidence intervals too narrow if it is ignored. This is a general statistical consideration, not a reported feature of this trial. The registry does not report a model for the primary outcome or an assessment of over-dispersion.

What is known about the analysis plan?

The registry record lists 0 analyses and does not report a statistical analysis plan, interim analyses, adjustment strategy, or sample-size justification. General planning illustrations may use an observed effect and prespecified assumptions, but they are not observed power and cannot replace a trial’s own design justification. The registry record does not report enough outcome analysis to interpret an effect-based planning illustration for the primary measure.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes multiple solicited local and systemic reactions, and the registry indicates that the outcome was not reduced to one comparison because it has several categories or time points. When multiple outcomes or contrasts are examined, the chance of at least one apparently unusual result can increase. In general, statistical plans may address this through a prespecified primary contrast or multiplicity adjustment. Neither a primary contrast among the reaction categories nor a multiplicity strategy is reported in the registry record. No category-specific inferential results are reported.

The registered safety population is described as all enrolled and vaccinated participants with available reaction data, an intent-to-treat population. This wording establishes that reaction data availability matters for inclusion in the safety analysis. It does not state how many participants lacked data for each reaction, why data were missing, or how missing observations were handled. Missing-data methods and sensitivity analyses are not reported in the registry record.

The adverse-event listing gives group-specific at-risk counts for serious events and other events. The at-risk count for other events differs from the group description’s participant count in the 5th Dose Pertussis Vaccine Group. The registry does not explain this difference. The listed counts should therefore be read as the event-record denominators rather than assumed to represent every enrolled participant or the same outcome-specific population.

Although the trial is labeled randomized, the registry record does not report the analysis population for any comparative efficacy-style estimate, since no such primary comparison is posted. It also does not report whether analyses were adjusted for baseline characteristics. These omissions limit assessment of missing-data bias, multiplicity, and the robustness of any potential group contrast.

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-event entries list 0 affected participants among 117 at risk in the 6th Dose Pertussis Vaccine Group and 0 among 98 at risk in the 5th Dose Pertussis Vaccine Group. The registry lists no serious adverse-event terms. These are observed counts in the registry, not estimates of the probability of a serious event and not evidence that such events are impossible. The record does not report confidence intervals or other measures of precision for these counts.

For other adverse events, the registry lists 89 affected among 117 at risk in the 6th Dose Pertussis Vaccine Group and 87 affected among 97 at risk in the 5th Dose Pertussis Vaccine Group. The record does not report a statistical comparison for these entries, and they should not be treated as a substitute for the solicited primary endpoint results. The definition of the aggregate other-event category is not given in the adverse-event listing.

Death counts are not reported in the registry record. The posted safety information is therefore limited to the event categories and counts recorded. It does not establish causation, characterize severity beyond the serious-event classification, or provide a complete account of risks beyond the recorded observation and reporting process.

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

The record supports a narrow descriptive conclusion: it documents the trial’s design, its solicited reaction endpoint, and adverse-event counts for groups distinguished by prior pertussis-vaccine history. It reports 0 serious events in each group’s serious-event entry and reports other-event counts of 89 and 87, with the corresponding at-risk counts recorded separately. These figures describe the registry entries; they are not a comparative analysis of the primary endpoint.

The primary measure sought participants reporting solicited local or systemic reactions during Days 0 to 14 Post-vaccination. The outcome includes several reaction types, but no single comparison is reported. Consequently, the posted record does not establish the size or precision of a difference in solicited reactions between the groups. It also does not report category-specific estimates or an analysis comparing REPEVAX® with COVAXIS®.

The design is randomized and parallel, but the groups are defined by prior vaccination history. Without a reported analysis, it is not possible to determine whether any difference in the adverse-event counts is statistically distinguishable from chance or whether it reflects prior history, product use, reporting, or other factors. The record does not provide information on baseline balance or adjusted analyses to clarify those possibilities.

These limitations do not erase the descriptive value of the registry entries, but they define what can be inferred from them. A zero count in the serious-event category does not prove that serious events cannot occur, and the other-event counts do not establish causation. The registry record does not report precision intervals, missing-data handling, or a statistical plan. The results should therefore be read as limited safety reporting rather than as a definitive comparative estimate.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a clearly defined post-vaccination observation window with a broad set of solicited reactions, yet the registry does not provide a single inferential comparison for that primary outcome. That distinction matters: naming an endpoint and recording event counts are not equivalent to reporting an estimated group effect with uncertainty.

The trial also places participants into groups with different pertussis-vaccine histories. That context is central to the question, but it complicates interpretation of a simple contrast. Group differences could reflect prior history or other factors, and the registry record does not report an adjusted analysis that would help separate those possibilities. Randomized allocation is recorded, but details about assignment and allocation across vaccine products are not reported.

The safety entries illustrate why denominators and outcome definitions need attention. The at-risk counts differ across event categories and groups, and the record does not explain the difference between the group description and the other-event denominator for the 5th Dose Pertussis Vaccine Group. In addition, the aggregate adverse-event entries should not be conflated with the multi-category solicited primary measure.

For biostatistical interpretation, the key lesson is to distinguish descriptive safety counts from a prespecified, analyzed comparison. Without a reported estimate, confidence interval, or analysis plan, the record cannot show how precise a group contrast would be or how multiplicity and missing data were addressed. Those gaps should constrain claims drawn from the posted results.

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 primary endpoint is described as a count of participants with solicited reactions, but it spans multiple local and systemic reaction categories. The registry says it was not reduced to one comparison. This prevents a concise inferential reading of the primary question and leaves no reported category-specific effect estimates or precision measures.

The public record lists no analyses and does not report a statistical analysis plan, sample-size justification, interim analyses, multiplicity handling, or adjustment strategy. It does not explain how reaction data were collected beyond identifying the solicited categories and observation window. Because the study was unmasked, expectations could influence reporting of subjective symptoms; the record does not describe procedures to address that concern.

The safety population includes enrolled and vaccinated participants with available reaction data, but the record does not describe missingness by outcome or how missing observations were handled. For other adverse events, the reported at-risk denominator in the 5th Dose Pertussis Vaccine Group is 97, while the group description identifies 98 participants. The registry does not explain this discrepancy, so the event entry should not be silently reconciled with the group description.

Serious-event counts are reported without precision estimates, and the registry does not report death counts. The adverse-event listing does not define the aggregate other-event category or establish that it matches the solicited primary outcome. Finally, the record does not report product-specific outcomes or the distribution of REPEVAX® and COVAXIS® across groups. These limitations restrict both comparative interpretation and assessment of completeness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Post-marketing Evaluation of Reactions Following Receipt of Recommended Adolescent Pertussis Vaccine — NCT00304265.
• Registry record last updated 2016-04-14; status last verified 2016-04.
• Results first posted 2011-04-07.
• 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

NCT00304265 is a completed, randomized, open-label, parallel-group phase 4 trial of post-marketing reactions following adolescent pertussis vaccination. It enrolled 215 participants and began in 2006-03, with primary completion in 2006-10. The groups were labeled the 6th Dose Pertussis Vaccine Group and the 5th Dose Pertussis Vaccine Group, reflecting different prior pertussis-vaccine histories.

The primary endpoint was the number of participants reporting solicited local or systemic reactions during Days 0 to 14 Post-vaccination. The registry record reports no single reduced comparison for this multi-category outcome and lists 0 analyses. Serious-event counts were 0 in both groups; other adverse-event counts and at-risk denominators were also listed. Comparative estimates, confidence intervals, missing-data methods, and a statistical analysis plan are not reported in the registry record.