A Trial to Evaluate the Safety and Immunogenicity of ADACEL® Vaccine in Persons 65 Years of Age and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Evaluate the Safety and Immunogenicity of ADACEL® Vaccine in Persons 65 Years of Age and Older (NCT00457249), a randomized phase 4 study. The primary outcome is Geometric Mean Titers (GMTs) of Tetanus, Diphtheria, and Pertussis Antibodies Pre- and Post-Vaccination With ADACEL® or DECAVAC® Vaccine.

2. Clinical Question

The clinical question is descriptive: the stated purpose is to describe safety and immunogenicity among individuals aged 65 years and older. Immunogenicity refers to the antibody response measured after vaccination. The listed endpoint includes antibodies to all three diseases for ADACEL®, while DECAVAC® contains tetanus and diphtheria toxoids. The registry record does not state a single primary contrast, a threshold for a clinically meaningful difference, or a hypothesis that the trial was designed to test. It also does not report the protocol’s rationale for choosing the comparator or the Day 35 assessment. Accordingly, the record supports a description of the trial question and outcome measures, but not a conclusion about comparative antibody responses.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 4 trial. The registry record lists enrollment as 1564 and status as completed. The start is recorded as 2007-03, and primary completion as 2008-09. Sanofi is listed as the sponsor. The trial concerns pertussis, tetanus and diphtheria in persons aged 65 years and older.

Participants were assigned to an ADACEL® Vaccine Group or a DECAVAC® Vaccine Group. The registry record labels the allocation randomized and the model parallel, meaning the two groups are treated as separate arms rather than as a crossover sequence. It labels masking quadruple, but does not identify which participant, clinical, outcome-assessment or analysis roles were masked, or describe how masking was maintained. The arm descriptions contain no additional information.

The registry record identifies ADACEL® as a tetanus, reduced diphtheria and acellular pertussis vaccine and DECAVAC® as a tetanus and diphtheria toxoid vaccine. The primary outcome is antibody geometric mean titers with 95% confidence intervals, assessed in the per-protocol population at Day 35 post-vaccination. The record lists four outcome measures, but the available description does not give their separate definitions or numerical findings. No analysis records are listed.

These design labels describe the structure of the study, not the details of its implementation. The randomization method, allocation concealment, masking procedures, planned group sizes, eligibility criteria and sample-size justification are not reported in the registry record. Nor does the record explain whether the intended analysis was designed to assess superiority, non-inferiority, equivalence or another objective. Those details cannot be inferred from the randomized, masked and parallel design labels alone.

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 1563 participants were enrolled; 1561 were vaccinated with data analyzed and presented in this report.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: GMTs and their 95% Confidence Intervals were assessed in the 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 Tetanus, Diphtheria, and Pertussis Antibodies Pre- and Post-Vaccination With ADACEL® or DECAVAC® Vaccine, measured over Day 35 post-vaccination.

The primary endpoint is geometric mean titers (GMTs) of antibodies to tetanus, diphtheria and pertussis, measured before and after vaccination with ADACEL® or DECAVAC®. The stated assessment time is Day 35 post-vaccination, and the population is the per-protocol population. The record specifies 95% confidence intervals for the GMTs.

A geometric mean is a way to summarize measurements that are positive and may vary across a wide range. Rather than taking an ordinary arithmetic average, it works on the logarithmic scale and then expresses the summary on the original scale. This can be useful for antibody titers because such values are often treated as multiplicative measurements. That is a general statistical explanation; the registry record does not state the precise data transformation or computational procedure used in this trial.

A confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate, while a wider interval indicates more uncertainty. The registry record names 95% confidence intervals but does not provide their numerical limits for the primary outcome.

Measuring titers before and after vaccination can describe antibody levels at both time points. The record does not report the actual values, changes, or a single comparison that combines the vaccine groups and time points. It also does not identify a response threshold or explain how the several antibody measures were to be interpreted together. The endpoint description therefore clarifies what was intended to be measured, but does not establish the magnitude or precision of any observed response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the trial as randomized and parallel-group. In general, random assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. It does not guarantee identical groups, and the credibility of the comparison also depends on how the sequence was generated and concealed. The method of randomization, concealment procedures and planned allocation ratio are not reported in the registry record.

The trial is labeled quadruple-masked. In general, masking can reduce the chance that expectations influence participant reports, clinical care, outcome assessment or interpretation. The label alone does not reveal which roles were masked or how the masking was maintained. Those implementation details are not reported in the registry record. The parallel design means the registry identifies distinct vaccine groups; it does not give further details about follow-up, adherence or treatment switching.

The primary summary measure is the geometric mean titer. In general, antibody titers can have a right-skewed distribution, where a smaller number of high values pull an arithmetic mean upward. A geometric mean summarizes values after taking logarithms, averaging on that scale, and returning to the original scale. This makes the summary naturally suited to multiplicative differences. The registry record names GMTs, but the precise transformation, handling of values below assay limits, and laboratory procedures are not reported in the registry record.

The endpoint includes 95% confidence intervals. In general, a confidence interval gives a range of estimates compatible with the observed data under a specified statistical model and its assumptions. It communicates precision, not the probability that a particular treatment effect is true. The width depends on the variability and amount of information in the analysis, among other factors. The registry record does not provide the GMT estimates or interval limits, and therefore does not permit assessment of their precision.

The stated primary population is per-protocol. In general, a per-protocol analysis includes participants who meet prespecified conditions for adherence and study conduct. It can describe outcomes among participants who followed the protocol, but the exact population depends on rules established before analysis. Those rules, exclusions and final group sizes are not reported in the registry record. A per-protocol result should not automatically be treated as equivalent to an analysis of all randomized participants.

The outcome description refers to measurements before and after vaccination and includes three antibody targets. Such a structure can yield multiple estimates and potential comparisons. Statistical interpretation depends on knowing which comparisons were prespecified, whether changes from baseline or post-vaccination levels were the principal contrast, and how the multiple measures were handled. The registry record does not report those details, and its primary outcome is not reduced to one comparison. No analysis records are listed.

In general, multiplicity arises when several outcomes, time points or comparisons are considered. The more opportunities there are to identify a nominally unusual result, the more important it becomes to specify which results are primary and how the error rate is handled. No multiplicity procedure is reported in the registry record. The outcome description alone is not enough to determine whether adjustment was planned or appropriate.

For safety, counts of participants affected are descriptive. They can be useful for showing how many participants in each arm had a reported event, but interpretation depends on consistent event definitions, follow-up duration, ascertainment and handling of repeat events. The record gives participant counts at risk and affected for serious and other adverse events, but does not report event definitions, exposure time, statistical comparisons or missing-data handling. The percentages listed for selected serious-event terms also lack a reported denominator or calculation method in the available record.

The sample-size assumptions described in the record are planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of the observed effect. Such illustrations are not observed power and do not establish the trial’s original design rationale. The sample-size justification and whether these illustrations informed the trial are not reported in the registry record. No recalculated primary comparison is available to interpret.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes antibody titers for tetanus, diphtheria and pertussis, measured before and after vaccination. The registry record also lists four outcome measures and indicates that the primary outcome has several categories or time points rather than a single reduced comparison. With multiple outcomes, time points or contrasts, multiplicity can affect how nominal statistical evidence should be interpreted. In general, a prespecified testing strategy helps distinguish confirmatory questions from additional descriptive analyses. The registry record does not report a multiplicity adjustment, testing hierarchy or other strategy for handling multiple comparisons.

Missing-data methods are also not reported in the registry record. The record does not state how participants without a Day 35 measurement were handled, whether any values were imputed, or how missing measurements affected the per-protocol population. It does not provide the number of participants contributing to the primary endpoint by arm. The enrollment figure and safety denominators do not, by themselves, establish the analysis population for the antibody outcomes.

The registry names the per-protocol population for the primary endpoint, but does not give the criteria used to define it, exclusions after randomization, or an intention-to-treat analysis. In general, different analysis populations answer different questions and can be affected differently by nonadherence, withdrawals and missing measurements. The details required to assess those issues are not reported in the registry record.

No analysis records are listed. Consequently, there are no posted primary-outcome estimates, confidence intervals or tests from which to assess how the planned outcome structure, missing observations or analysis populations were handled.

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: cholelithiasis (0.5%), appendicitis (0.5%), atrial fibrillation (0.3%), cardiac failure congestive (0.3%), cerebrovascular accident (0.3%).

The registry reports serious adverse events for 1170 participants at risk in the ADACEL® group, with 49 affected; in the DECAVAC® group, 391 were at risk, with 20 affected. For other adverse events, 615 participants were affected among 1170 at risk in the ADACEL® group, and 200 among 391 at risk in the DECAVAC® group. These are counts of participants, not a statistical test of the difference between groups.

The record also lists selected serious-event terms: cholelithiasis and appendicitis at 0.5% each; atrial fibrillation, cardiac failure congestive, cerebrovascular accident and coronary artery disease at 0.3% each. These percentages are reported as event-term frequencies, but the registry record does not state their denominator or calculation method. The listing should not be read as a complete accounting of all serious events or as evidence that vaccination caused any particular event.

For a comparative safety interpretation, it would be important to know event definitions, observation periods, ascertainment procedures, whether participants could contribute multiple events, and the analysis method. These details are not reported in the registry record. Death counts are not reported in the registry record. The available counts therefore support a descriptive reading only, not a causal or adjusted comparison.

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

The trial record documents a randomized, quadruple-masked, parallel-group phase 4 comparison of ADACEL® and DECAVAC® in persons aged 65 years and older. It identifies antibody GMTs and 95% confidence intervals as the primary outcome, with measurement at Day 35 post-vaccination in the per-protocol population. It also reports participant counts for serious and other adverse events. These details establish what the trial set out to describe and some of the safety counts recorded.

They do not establish the comparative antibody response. Numerical GMTs, confidence-interval limits and primary statistical comparisons are not reported in the registry record. Without these results, the direction and magnitude of any difference, and the precision of the estimates, cannot be assessed. The outcome spans multiple antibody targets and time points, and the record does not identify one summary comparison or describe how the outcomes were analyzed together.

The safety counts similarly do not establish whether one group had a higher or lower risk, whether any observed difference is statistically distinguishable from chance, or whether an event was caused by vaccination. The registry does not report the analytical details and context needed for such interpretations. The selected event-term percentages are descriptive entries, not evidence of causation.

In general, a trial’s design and endpoint definitions should be distinguished from its results. Randomization and masking describe intended safeguards against bias; they do not substitute for posted estimates or information about analysis populations and missing data. The record’s completed status does not itself reveal the outcome findings.

Accordingly, the available registry information supports a concise account of the study question and reported safety counts, but not a conclusion about comparative immunogenicity or safety. Numerical primary results and further analytical detail are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a randomized comparison with a descriptive antibody endpoint in an older-adult population. The registry identifies two vaccines with different listed antigen compositions and assesses antibody titers for tetanus, diphtheria and pertussis. That makes clear why outcome definitions matter: measurements for different antigens and time points are distinct quantities and cannot be treated as interchangeable.

The endpoint uses geometric mean titers and 95% confidence intervals. In general, this pairing expresses antibody levels on a scale suited to multiplicative measurements while conveying uncertainty around each estimate. The usefulness of that approach depends on seeing the estimates, intervals and analysis population. Here, the primary outcome values are not reported in the registry record, so its statistical precision and comparative meaning cannot be judged from the available record.

The record also illustrates the distinction between a design label and an analysis plan. Randomization and quadruple masking are identified, but the operational details and statistical procedures are not. The primary outcome includes several categories or time points, yet no single comparison is specified in the available description, and no analysis records are listed. Those omissions prevent assessment of how multiple measures were interpreted.

Safety reporting offers another statistical distinction: counts of affected participants are not the same as adjusted or causal comparisons. The serious and other adverse-event counts describe participants in each group, while selected serious-event terms are listed with percentages. Without a reported analysis method, event definitions and relevant denominators, those figures should be read descriptively.

For researchers, the central lesson is that a registry description can identify the design and intended estimands without supplying the evidence needed to evaluate them. Interpretation requires outcome estimates, uncertainty, analysis-population definitions and transparent handling of multiplicity and missing data.

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 statistical interpretation is that numerical primary-outcome results are not reported in the registry record. The GMT estimates and 95% confidence intervals for antibody responses are absent, as are reported tests or contrasts. The primary endpoint covers several antibody targets and time points, but the record does not reduce these to a single comparison. This prevents a direct assessment of the central immunogenicity question.

The record identifies a per-protocol population but does not define its criteria, give the number analyzed, describe exclusions, or state how missing antibody measurements were handled. An intention-to-treat analysis is not described. These omissions limit assessment of selection after randomization and the representativeness of the primary analysis.

Although the study is labeled randomized and quadruple-masked, the method of sequence generation, allocation concealment and masking procedures are not reported in the registry record. The record also does not provide eligibility criteria, treatment adherence information, follow-up details or sample-size justification. It is not possible to determine from the design labels alone how these features were implemented.

Safety reporting is limited to affected-participant counts and selected serious-event terms. The record does not describe event definitions, ascertainment, exposure time, repeat events, statistical comparisons or the denominator used for the listed percentages. Death counts are not reported in the registry record. Therefore the safety information is descriptive and cannot support a detailed comparative or causal assessment.

Finally, the registry lists four outcome measures but no analysis records. The statistical plan, multiplicity approach and handling of missing data are not reported in the registry record. These limitations concern what can be interpreted from the record; they do not establish what analyses may have been performed elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Trial to Evaluate the Safety and Immunogenicity of ADACEL® Vaccine in Persons 65 Years of Age and Older — NCT00457249.
• Registry record last updated 2012-10-19; status last verified 2012-09.
• Results first posted 2012-10-19.
• 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

NCT00457249 is a completed randomized, quadruple-masked, parallel-group phase 4 trial sponsored by Sanofi. It enrolled 1564 people aged 65 years and older and compared ADACEL® with DECAVAC®. The recorded start is 2007-03, and primary completion is 2008-09.

The primary outcome is geometric mean titers of antibodies to tetanus, diphtheria and pertussis, with 95% confidence intervals at Day 35 post-vaccination in the per-protocol population. Numerical primary results and analysis records are not reported in the registry record.

The registry reports serious adverse events affecting 49 of 1170 at risk in the ADACEL® group and 20 of 391 in the DECAVAC® group. Other adverse events affected 615 of 1170 and 200 of 391, respectively. The event counts are descriptive; further analytical and methodological detail is not reported in the registry record.