Descriptive, Post-marketing, Surveillance Safety Study of Menactra Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Descriptive, Post-marketing, Surveillance Safety Study of Menactra Vaccine (NCT00254995), a registered phase not stated study. The primary outcome is Summary of Diagnoses With Significantly Elevated Findings From Risk-Window vs. Control-Window Comparisons: All Ages Combined - Short-Term Passive Surveillance.

2. Clinical Question

The study’s stated aim was to further characterize the safety profile of Menactra and identify signals of potentially vaccine-related adverse events not detected during pre-licensure studies. The primary outcome description focuses on diagnoses occurring in the period after vaccination and compares their rates across post-vaccination windows.

This is a safety-surveillance question, not a comparison of vaccine efficacy. The record describes routine-use monitoring and does not report a randomized allocation. The primary comparison uses post-vaccination time windows within vaccine recipients, rather than comparing a vaccine group with a randomized untreated group.

3. Trial Design

This was a completed, descriptive, post-marketing surveillance study of routine Menactra use. The registry lists Sanofi Pasteur, a Sanofi Company, as sponsor. The study began in 2005-07, and primary completion was 2013-05. Recorded enrollment was 62626. The intervention field states that none was administered in the study; participants received Menactra as part of routine medical care during the study period in Kaiser Permanente.

The primary outcome is described as short-term passive surveillance. For each diagnosis, the investigators calculated incidence rates using events and person-time in each 30-day comparison window. The risk window was Days 0-30 following vaccination, and the control window was Days 31-60 following vaccination. The registry says that vaccine recipients served as their own controls for this acute comparison. Clinical setting was designated in the outcome description as hospital or emergency room.

The registry also describes long-term surveillance using age-matched controls. It says that a control was matched to each vaccine recipient on age, sex, and month of vaccination, but the record’s arm description ends before the full selection description is available. The exact long-term comparison and its relationship to the primary outcome are therefore not fully reported in the registry record.

The record lists 9 outcome measures and 0 analyses. The primary outcome title refers to diagnoses with significantly elevated findings, but the diagnosis-specific results and their statistical estimates are not reported in the registry record. The allocation field is not stated, and the record notes that the arms are not a like-for-like control comparison. These features matter when interpreting any apparent contrast: this is surveillance in routine care, not a randomized trial designed to estimate a treatment effect.

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: Databases were reviewed to identify persons who received Menactra vaccine within Kaiser Permanente and to identify all medical care events for the 6-month period following vaccination or, if applicable, through the end of pregnancy. Subjects served as their own control for 0-30 days surveillance, age-matched control served for the 6-month period.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All persons who received Menactra vaccine during the study period were included in the analysis.

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.

Population: Subjects who received Menactra vaccine during the study period from the Kaiser Permanente databases.

6. Primary Endpoint

The registry lists the primary outcome as Summary of Diagnoses With Significantly Elevated Findings From Risk-Window vs. Control-Window Comparisons: All Ages Combined - Short-Term Passive Surveillance, measured over Day 0 up to Day 60 post-vaccination.

The primary endpoint measures diagnosis incidence rates across post-vaccination windows. For each diagnosis, the count of events is divided by person-time, and the result is expressed as events per 1,000 person-months. This exposure-adjusted form of a rate allows comparison when the amount of observed time may differ between windows or groups. It is not the same quantity as the proportion of people who experience an event.

The specified short-term comparison is between Days 0-30 and Days 31-60 after vaccination. The former is the risk window; the latter is the control window. Each recipient serves as their own control for this comparison, so the contrast is within individuals over time rather than between separately assigned treatment groups. The outcome description refers to diagnoses recorded in hospital or emergency-room settings.

Such surveillance endpoints are used to look for patterns that may warrant closer evaluation after routine use. A higher rate in the risk window can be a signal for investigation, but the rate comparison alone does not establish that vaccination caused the diagnosis. Interpretation also depends on the diagnosis-specific rate estimates, uncertainty, the surveillance process, and the possibility of changes over time.

The registry record does not report the diagnoses identified as elevated, their event counts, person-time, rate estimates, confidence intervals, or test results. Consequently, the endpoint definition is available, but the magnitude and precision of its reported findings cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome uses an incidence rate. General: an incidence rate relates the number of observed events to the person-time during which events could be observed. Person-time incorporates both the number of people observed and the length of their observation. This can make rates useful when observation duration differs. The registry specifies that diagnoses were counted in each 30-day comparison window and rates were expressed as events per 1,000 person-months.

What does the within-person comparison mean?

For short-term surveillance, each Menactra recipient served as their own control. The rate during Days 0-30 after vaccination was compared with the rate during Days 31-60. General: a self-controlled comparison uses different periods for the same person, rather than assigning people to separate treatment groups. Stable personal characteristics are shared across those periods, but this design does not eliminate possible influences that vary with time. The registry record does not report adjustments for such influences or enough analysis detail to determine how they were handled.

The control window is a period after vaccination, not a period before vaccination. That distinction is important when interpreting the comparison: the question is whether diagnosis rates differed between these post-vaccination intervals, not whether vaccinated people differed from an untreated randomized group. The registry describes a separate age-matched control approach for long-term surveillance, but the available description is incomplete. Its full implementation is not reported in the registry record.

How should a rate be distinguished from a risk?

General: a rate has person-time in its denominator, while a risk or proportion describes the share of people experiencing an event over a defined period. An event rate can account for differing time under observation, but it does not directly state the probability that an individual will experience an event. The primary endpoint is specifically an event rate per 1,000 person-months, so it should not be read as a percentage of participants affected.

The registry says that the event count was divided by person-time for each diagnosis and comparison window. It does not report the event counts, person-time, numerical rates, or uncertainty estimates for the primary diagnoses. Therefore, no recalculation from posted summary statistics is available. There is also no basis in the record for converting its endpoint into a participant-level risk.

What does statistical significance tell a reader?

General: a statistical test assesses how compatible observed data are with a specified null model, under the assumptions of that test. A finding described as statistically significant is not, by itself, a measure of clinical importance, the size of an effect, or the probability that a causal explanation is true. A confidence interval, when reported, describes uncertainty around an estimate under the analysis model; a narrower interval generally indicates greater precision than a wider interval.

The primary outcome title refers to significantly elevated findings, but no diagnosis-specific estimates, confidence intervals, test statistics, or p-values are reported in the registry record. The test procedures and any adjustment for multiple comparisons are also not reported. Thus, the title cannot substitute for the numerical results or a description of the inferential method.

Why can over-dispersion matter?

General: count data are sometimes more variable than a simple model assumes. This is called over-dispersion. If a model fails to account for extra variability, uncertainty estimates and statistical tests may be unreliable. Conversely, an appropriate model can account for a variance structure that is more complex than the simplest count model. The registry record does not report a model, a dispersion estimate, or a method for addressing over-dispersion. No conclusion about whether it was present or how it was handled can be drawn.

The outcome description identifies rates calculated from events and person-time, but it does not specify whether the analysis used a model or a direct rate comparison. The analytical distribution, handling of repeated events, and adjustments for other variables are not reported in the registry record. These details affect how a reader would assess the precision and validity of statistical comparisons.

What can planning illustrations establish?

General: sample-size planning calculations describe the number of participants or events that might be needed under stated assumptions to detect a chosen effect with a chosen level of statistical power. They are not a measure of the power actually achieved by a completed study. The registry’s planning illustration is explicitly based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; it considers the stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events, while other tables use participants per arm.

Those assumptions describe a planning illustration, not the study’s original design. The registry record does not report the trial’s own sample-size justification or a prospective statistical plan. The illustration should not be treated as observed power, nor as evidence that the surveillance analysis had a particular ability to detect a signal.

In general, statistical interpretation requires both an effect estimate and information about its uncertainty, alongside a clear account of the analysis. For this study, the endpoint definition and comparison windows are described, but the primary diagnosis-specific estimates and analysis methods are not reported in the registry record. That limits what can be concluded about the size, precision, and robustness of the findings.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 9 outcome measures and 0 analyses. The primary outcome concerns diagnoses with significantly elevated findings, which implies that more than one diagnosis may be considered, but the actual diagnosis list and analysis results are not reported in the registry record. The number of comparisons performed is therefore not established by the posted results.

General: when many outcomes or diagnoses are examined, the chance of observing at least one apparently unusual result can increase, even if no underlying association exists. Statistical methods can address this issue by adjusting significance thresholds or by controlling an error rate. The record does not report whether multiplicity was considered, whether any adjustment was used, or whether the diagnoses were prespecified. It is not possible to determine the effect of multiplicity on the findings without this information and the underlying analysis results.

Missing-data handling is also not reported in the registry record. The record does not explain how incomplete follow-up, missing diagnosis information, or differences in person-time were handled beyond stating that event counts were divided by person-time. It does not report exclusions from the primary analysis or how missing records affected the analytic population.

The described primary population is all persons who received Menactra during the study period. The recorded enrollment is 62626, but the registry does not provide a participant flow account for the primary analysis. It is not reported whether every enrolled person contributed to every diagnosis-specific comparison.

The record does not report an interim-analysis plan, a prospective statistical analysis plan, or the sample-size justification for the study. The planning illustration described in the registry is not the study’s own design justification. These omissions leave the multiplicity strategy, analysis population details, and missing-data approach uncertain.

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 serious adverse event terms

Serious events with the highest arm-level rate: psychiatric (0.2%), trauma (0.1%), appendicitis (0.1%), congenital anomaly (0.0%), abscess/cellulitis (0.0%).

The registry’s serious adverse-event summary lists Menactra Vaccine Recipients with 31561 at risk and 273 affected. Under the other category, it lists 31558 at risk and 0 affected. These entries are descriptive counts in the registry record. The relationship between the other category and the vaccine-recipient group is not fully explained, and the record cautions that the arms are not a like-for-like control comparison. They should not be interpreted as a randomized treatment contrast.

The listed top serious terms and percentages are Psychiatric, 0.2%; Trauma, 0.1%; Appendicitis, 0.1%; Congenital Anomaly, 0.0%; Abscess/Cellulitis, 0.0%; and Elective Procedure, 0.0%. These percentages are registry entries; the record does not provide corresponding event counts for each term. A listed percentage does not indicate whether the event was caused by vaccination.

The death field is not reported in the registry record. It should not be read as a count of zero. Likewise, these adverse-event summaries do not replace the diagnosis-specific short-term rate comparisons, whose estimates are not reported in the registry record. Serious-event terminology, event-rate outcomes, and causal attribution are separate concepts.

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

The record establishes that the study was designed to monitor safety during routine Menactra use and to look for potentially vaccine-related adverse-event signals. It also defines a short-term comparison of diagnosis rates in Days 0-30 and Days 31-60 after vaccination. Those details describe the question and the surveillance framework; they do not establish the presence, size, or cause of any particular signal.

The primary outcome title refers to significantly elevated findings, but the diagnosis-specific results are not reported in the registry record. Without event counts, person-time, rate estimates, confidence intervals, or test results, readers cannot assess how large or precise those findings were. The posted record therefore does not support a numerical conclusion about the primary endpoint.

The study is observational surveillance of routine care. The registry does not state an allocation method, and its own note says the arms are not a like-for-like control comparison. The primary short-term analysis uses participants as their own controls across post-vaccination periods. A difference between those periods would describe a temporal association in the observed data; it would not, on its own, establish that vaccination caused a diagnosis.

The serious adverse-event summary provides descriptive counts and listed terms, but the record does not explain the other category sufficiently for a direct group comparison. The death field is not reported in the registry record. These details should not be combined with the missing primary endpoint results to infer a broader conclusion about safety.

General: surveillance studies can identify patterns that merit further assessment, while causal conclusions usually require careful consideration of design, bias, timing, measurement, and uncertainty. For this study, the registry describes the intended monitoring approach but does not provide enough analysis detail or primary numerical results to judge the strength of any diagnosis-specific finding. The result does not establish that a particular event was caused by vaccination, and the incomplete record does not establish that no signal occurred.

13. Why This Trial Matters Statistically

Post-marketing surveillance addresses a statistical problem that differs from estimating efficacy in a randomized trial. Routine-use data can support monitoring for events across a broad population and over extended periods, while the absence of randomized allocation makes causal interpretation more difficult. The registry describes a safety aim: identify potentially vaccine-related adverse-event signals not detected during pre-licensure studies.

The short-term design also illustrates the logic of self-controlled comparisons. Comparing each recipient across post-vaccination windows can reduce the influence of characteristics that do not change over time. At the same time, time-varying factors can still affect the contrast. Understanding what the design can and cannot control is essential when interpreting safety signals from observational data.

The rate endpoint is another important statistical choice. Expressing events relative to person-time distinguishes an incidence rate from a participant-level proportion and can accommodate varying observation time. For that estimate to be judged, however, readers need the diagnosis-specific event counts, person-time, rates, and uncertainty. Those primary results are not reported in the registry record.

This record therefore offers a useful example of why a study’s objective and result title are not a substitute for a complete statistical report. Although the primary outcome title refers to significantly elevated findings, the registry lists 9 outcome measures and 0 analyses, and does not provide the underlying diagnosis-specific estimates or analysis methods. Without those details, readers cannot evaluate effect magnitude, precision, multiplicity, or robustness.

The statistical lesson is not a conclusion for or against a safety signal. It is that signal detection, estimation, and causal interpretation are distinct tasks. Clear reporting of the analysis population, event counts, person-time, estimates, uncertainty, and multiplicity approach is needed to move from a surveillance question to an interpretable result.

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 limitation for interpreting this record is that the diagnosis-specific results are not reported in the registry record. Although the outcome title refers to significantly elevated findings, it does not name those diagnoses or give their event counts, person-time, rates, confidence intervals, or test results. The size and precision of the stated findings therefore cannot be assessed.

The statistical analysis is incompletely described. The registry explains how incidence rates were calculated and identifies the comparison windows, but does not report the inferential procedures, model, covariate adjustment, treatment of repeated events, or assessment of over-dispersion. Multiplicity handling is also not reported, despite the multiple outcome measures listed. It is not possible to judge the robustness of individual findings from the registry description alone.

The design is observational, and the allocation field is not stated. The registry notes that the listed arms are not a like-for-like control comparison. The short-term comparison uses recipients as their own controls, while the long-term control description is incomplete. Potential influences that vary over time are not addressed in the posted methods description; their actual contribution to any finding is not reported in the registry record.

The record does not report missing-data procedures, participant flow into each analysis, or the number of people contributing to each diagnosis-specific comparison. It also does not provide the study’s own sample-size justification or prospective statistical plan. The planning illustration is not a substitute for those details and is not observed power.

The adverse-event summary has additional interpretive limits: the other category is not fully characterized, term-specific counts are not reported, and the death field is not reported in the registry record. These omissions constrain interpretation of the safety summary without establishing that any unreported event did or did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Descriptive, Post-marketing, Surveillance Safety Study of Menactra Vaccine — NCT00254995.
• Registry record last updated 2016-04-19; status last verified 2016-04.
• Results first posted 2014-11-11.
• 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

NCT00254995 is a completed descriptive, post-marketing safety-surveillance study of routine Menactra vaccination, sponsored by Sanofi Pasteur, a Sanofi Company. The recorded enrollment is 62626. The study began in 2005-07, and primary completion was in 2013-05. The registry lists Meningitis and Meningococcal Disease as conditions.

The primary outcome describes diagnosis incidence rates per 1,000 person-months, comparing Days 0-30 with Days 31-60 after vaccination. Vaccine recipients served as their own controls for this short-term comparison. The specific diagnoses and numerical results for the elevated findings are not reported in the registry record.

The registry lists 9 outcome measures and 0 analyses. It also includes a serious adverse-event summary, but the other category is not fully explained and the death field is not reported. The record supports a description of the surveillance design, but not a quantitative assessment of the primary findings.