Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial (NCT01011335), a randomized phase 1, phase 2 study. The primary outcome is Assessment of Safety Through Clinical Examinations, Clinical Laboratory Results, Self-reported Diary Reactogenicity Data and Adverse Event Reports.

2. Clinical Question

This question has a dose-selection and early evaluation focus. It is not a direct test of whether vaccination prevents Staphylococcus aureus infection: the registry summary describes prevention as the development goal for the vaccine components, but the stated primary outcome is safety. The record does not report infection-prevention results.

3. Trial Design

The trial is listed as randomized, multicenter, parallel, and quadruple-masked, and as Phase 1-2. It was sponsored by the Henry M. Jackson Foundation for the Advancement of Military Medicine. The registry record lists enrollment of 176, a start date of 2009-11, primary completion in 2011-03, and status as completed.

Participants were assigned to vaccine or placebo groups. The active formulations included monovalent rAT, monovalent rLukS-PV, and bivalent rLukS-PV / rAT; placebo groups included alum placebo and normal saline placebo. The listed dose groups span several doses for the monovalent formulations and several doses for the bivalent formulation. The record does not provide a single pooled active-vaccine group for interpreting the results, and the posted adverse-event data are organized by formulation and dose.

In general, randomization is intended to reduce systematic differences between groups at assignment. A parallel design means groups receive their assigned interventions during the same trial period rather than crossing over between interventions. Masking is intended to limit the influence of knowledge of assignment on participant experience, clinical care, and outcome assessment. The record identifies quadruple masking but does not specify which roles were masked or describe the masking procedures.

The primary safety assessment drew on clinical examinations, laboratory results, participant-completed diaries, and adverse-event reports. Its stated timeframe was up to 6 months. Although the study summary also describes immunogenicity as a study aim, the specific immunogenicity measures and their results are not reported in the registry record. Nor does the record give further detail on allocation procedures, the number of centers, or the rationale for the chosen 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: Subjects who consented to the study but who were not randomized were those who either failed screening due to abnormal baseline laboratory results, or who met screening criteria but became ineligible to receive a study injection or were unavailable at the time of injection. Subjects who were unavailable at the time of injection were replaced.

Only the first 6 of 13 groups are shown.

Overall Study

Reasons for not completing this period:

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 Assessment of Safety Through Clinical Examinations, Clinical Laboratory Results, Self-reported Diary Reactogenicity Data and Adverse Event Reports, measured over Up to 6 months.

The primary outcome was an assessment of safety through clinical examinations, clinical laboratory results, self-reported diary reactogenicity data, and adverse-event reports. The registry lists the outcome unit as events and gives a timeframe of up to 6 months. The description says that adverse events, local reactogenicity, and systemic reactogenicity were assessed using provider examinations, laboratory results, and review of participant-completed diaries.

These sources capture different aspects of tolerability. Clinical examinations and laboratory results can identify findings assessed by study providers, while diaries can record local or systemic symptoms reported by participants. Adverse-event reports provide another route for documenting health events during follow-up. In general, combining these sources can give a broader safety profile than relying on one source alone; the sources do not necessarily measure the same kind of event or use identical ascertainment.

Safety outcomes are used in early vaccine evaluation because dose and formulation decisions require information about observed adverse events and reactogenicity. That general purpose does not make every event attributable to the study vaccine, and the registry record does not describe an attribution rule. The record also does not report a single numerical endpoint summary, a prespecified definition of the primary safety measure, or detailed results for the clinical, laboratory, and diary components separately. The specific immunogenicity outcome is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial record identifies random allocation, a parallel-group model, multicenter conduct, and quadruple masking. It lists a safety outcome measured as events, assessed through clinical examinations, laboratory results, diaries, and adverse-event reports. The posted adverse-event summaries are group-based counts. The record does not report a statistical analysis plan or inferential analysis for the primary outcome.

What does randomization contribute?

In general, randomization assigns participants to groups using a chance-based process. Its purpose is to reduce systematic differences in measured and unmeasured characteristics at the time of assignment. It does not guarantee that groups will have identical characteristics, particularly when group sizes are limited. The registry record says the trial was randomized but does not describe the sequence-generation method, concealment procedure, or any checks of baseline balance. Those details are not reported in the registry record.

What does masking mean for interpretation?

In general, masking can reduce the chance that expectations influence reporting, clinical decisions, or outcome assessment. The registry record labels the trial quadruple-masked. It does not identify the masked roles or explain how masking was maintained, so the label cannot establish which people were unaware of assignments or whether masking remained intact. This matters particularly for diary-based reactogenicity, because participant-reported symptoms can be influenced by awareness of treatment, while clinical laboratory measures have different sources of potential measurement variation.

How should the event counts be read?

The registry outcome is described in terms of events, while the adverse-event summaries list numbers at risk and numbers affected in each group. These summaries are useful for describing what was recorded, but a count of affected participants is not necessarily the same as a total count of events: one participant may experience more than one event. The registry record does not explain whether its group figures count people, events, or both in every category. It is therefore important to retain the record's distinction between outcome unit and group-level affected counts rather than treating them as interchangeable.

In general, a comparative analysis of event data would need to define the unit of analysis, the event categories, the follow-up period, and the comparison of interest. It could also need to address repeated events for the same participant. The registry record does not report these analysis details, nor does it provide a model, estimate, standard error, or confidence interval for a comparison. No adjusted or unadjusted effect estimate for the primary outcome is reported in the registry record.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the statistical method used. A narrow interval indicates more precision than a wide interval, but neither width nor location alone proves that an effect is clinically important. Since the registry record does not give confidence intervals or a comparative estimate for the primary outcome, the precision of a between-group difference cannot be assessed from these posted results.

Why can event-count methods matter?

In general, count outcomes can be analyzed using methods that account for the distribution of events and the amount of follow-up. Some count data are more variable than a simple model expects; this is called over-dispersion. When over-dispersion is present, a method that assumes less variability can make standard errors too small and intervals too narrow. Whether over-dispersion is relevant depends on the actual data and model. The registry record does not report event-level data, a fitted count model, or any assessment of over-dispersion, so no conclusion about its presence or treatment is possible.

What can planning calculations tell readers?

In general, sample-size calculations are planning illustrations based on assumptions about a target effect, significance level, allocation, and statistical method. They are not observed power and do not describe the certainty of a completed trial's result. The registry record does not report its own sample-size justification. The planning assumptions described for the separate illustration use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Because the posted primary outcome is not reduced to one comparison, these assumptions do not supply a trial-specific treatment estimate or a basis for treating a planning result as observed evidence.

The record also does not report an interim-analysis plan, multiplicity adjustment, missing-data method, analysis population, or prespecified covariate adjustment. These omissions limit reproducibility and make it difficult to determine how the posted descriptive counts relate to any complete analysis conducted by the sponsor.

10. Multiplicity, Missing Data and Analysis Populations

The study included several vaccine formulations and dose groups, alongside placebo groups. The primary safety assessment also drew on different sources and included adverse events, local reactogenicity, and systemic reactogenicity. In general, testing many outcomes, groups, or contrasts increases the chance of finding an apparently unusual result by chance if each is assessed separately. A prespecified analysis plan can define primary comparisons and, where appropriate, methods to address multiplicity. The registry record does not report a multiplicity strategy or identify one primary group comparison.

The record lists two outcome measures but does not give an analysis that reduces the outcome categories or time points to one comparison. It does not report which outcomes were included in a formal analysis, whether any comparisons were prespecified, or whether adjustment was used. These details are not reported in the registry record, so the descriptive results should not be treated as a set of confirmatory tests.

Missing-data handling is also not reported in the registry record. The posted summaries give numbers at risk, but the record does not explain the handling of incomplete follow-up, missing diaries, unavailable laboratory measurements, or participants without a recorded assessment. It does not report whether observations were excluded, imputed, or analyzed under another approach.

The analysis populations are not reported in the registry record. It is therefore unclear whether the posted summaries use all randomized participants, participants who received an intervention, or a defined subset with available outcome data. Without those definitions and a missing-data account, the impact of incomplete observation on the safety summaries cannot be assessed. No interim-analysis plan or stopping rule is reported either.

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: alcoholism (8.3%), thrombocytopenia (8.3%), non-cardiac chest pain (8.3%), pneumonia (8.3%), astrocytoma malignant (4.5%).

The registry lists serious and other adverse-event counts by group. For serious adverse events, affected counts are 0 in several vaccine and placebo groups, and nonzero counts appear in the Monovalent rLukS 50µg Dose, Bivalent rAT/rLukS 25µg Dose, Bivalent rAT/rLukS 50µg Dose, and Normal Saline Placebo groups. The group-specific numbers at risk are reported alongside those affected counts. These figures are descriptive and do not show whether an event was caused by an assigned intervention.

The record's serious-event term list includes Alcoholism, Thrombocytopenia, Non-cardiac Chest Pain, and Pneumonia, each reported as 8.3%, and Astrocytoma Malignant, reported as 4.5%. The registry record does not explain the denominator or provide enough detail to interpret these percentages as risks in a particular treatment group. Death counts are not reported in the registry record.

In general, serious adverse events and common reactogenicity symptoms are different safety summaries and should not be conflated. The listed group counts do not provide event timing, duration, severity grading, attribution, or a comparative statistical analysis. They describe what the registry record reports, not a causal conclusion.

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

The record documents a randomized, masked, parallel Phase 1-2 evaluation of several Staphylococcus aureus toxoid formulations in healthy volunteers, with placebo comparators. Its stated primary outcome concerns safety assessments through up to 6 months. The adverse-event summaries describe affected counts by group, while the registry record does not report a formal comparison or a confidence interval for the primary safety outcome.

These posted data can help readers understand which safety categories were recorded and how the listed counts are distributed across dose and placebo groups. They do not, on their own, establish a causal relationship between an intervention and an event. Small counts and descriptive summaries also do not quantify the precision of between-group differences. No treatment effect estimate for safety is reported in the registry record.

The study summary says the candidates were being evaluated for dose, safety, and immune response, with infection prevention as a development goal. The specific immunogenicity results and infection-prevention results are not reported in the registry record. The posted safety summaries therefore cannot answer whether the candidates generated a particular immune response or prevented infection.

In general, early evaluations can inform later research by characterizing observed events and identifying questions for further study. That general role should not be confused with proof of a treatment benefit or proof that no risk exists. The registry record does not report a selected optimal dose, a confirmatory efficacy comparison, or a basis for a clinical recommendation. The interpretation should remain limited to the recorded groups, outcomes, and follow-up described in the record.

13. Why This Trial Matters Statistically

This trial illustrates the statistical challenges of early evaluations with multiple formulations, dose groups, placebo groups, and safety categories. A single headline count cannot capture every aspect of safety when information comes from examinations, laboratory results, diaries, and adverse-event reports. Each source can contribute different observations, and a clear analysis needs to define how those observations are summarized.

It also shows why descriptive counts and comparative estimates answer different questions. Counts describe recorded events or affected participants within groups. A comparative estimate would quantify a contrast between groups, with uncertainty expressed through a standard error or confidence interval. The registry record reports group counts but not a comparative estimate for the primary outcome, so the strength and precision of a difference cannot be determined from the posted results.

Several dose groups create a multiplicity issue in general: readers need to know which comparisons were planned and how conclusions were protected against chance findings from many comparisons. The registry record does not report that plan. Definitions of the analysis population and missing-data handling also matter, especially when outcomes rely partly on participant diaries and follow-up assessments. Those details are not reported in the registry record.

Finally, the trial's stated aims include immunogenicity and dose evaluation, but its primary outcome is safety. Keeping those aims distinct prevents safety counts from being mistaken for evidence about immune response or infection prevention. The record is statistically informative about design and reported safety categories, while leaving important analysis details and outcome results unresolved.

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 registry record does not report the statistical analysis plan, a sample-size justification, or interim-analysis procedures. It also does not provide inferential results for the primary outcome, such as a prespecified contrast, effect estimate, or confidence interval. The posted safety counts are therefore not accompanied by a reported measure of comparative precision.

The record does not explain the allocation sequence or concealment, which roles were masked, or how masking was maintained. It also does not report baseline characteristics by group, center-level details, or whether the analysis accounted for the multicenter design. These missing descriptions limit assessment of group comparability and of how the design was reflected in analysis.

Outcome definitions and data handling are not fully described. The registry record does not specify the criteria used for serious adverse events, the attribution process, the handling of repeated events, or the denominators used for the listed serious-event percentages. It does not report missing-data methods, analysis populations, follow-up completeness, or separate detailed results for clinical, laboratory, and diary components. Death counts are not reported in the registry record.

Although the study summary identifies immunogenicity as an aim, the specific immune-response outcomes and results are not reported in the registry record. Nor are infection-prevention outcomes reported. These limitations mean the posted information supports a descriptive reading of the listed safety data, but not a complete assessment of comparative safety, immunogenicity, or efficacy.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial — NCT01011335.
• Registry record last updated 2023-03-07; status last verified 2023-02.
• Results first posted 2017-12-12.
• 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

The registry record describes a completed, randomized, multicenter, parallel, quadruple-masked Phase 1-2 trial of Staphylococcus aureus toxoid vaccine candidates in healthy volunteers. The listed formulations were monovalent rAT, monovalent rLukS-PV, and bivalent rLukS-PV / rAT, with alum and normal saline placebo groups. Enrollment was 176. The record lists a start date of 2009-11 and primary completion in 2011-03.

The primary outcome assessed safety through clinical examinations, laboratory results, participant diaries, and adverse-event reports over up to 6 months. Group-level summaries report serious and other adverse-event counts. A comparative analysis, analysis populations, missing-data approach, and multiplicity plan are not reported in the registry record. Specific immunogenicity and infection-prevention results are also not reported in the registry record.