COVID-19 Booster Study in Healthy Adults in Australia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for COVID-19 Booster Study in Healthy Adults in Australia (NCT05658523), a randomized phase 3 study. The primary outcome is SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination.

2. Clinical Question

The study is framed around immunogenicity as well as safety and reactogenicity. Its primary endpoint is an antibody measurement rather than a clinical outcome such as COVID-19 illness. The posted values therefore describe the antibody concentrations measured in each vaccine group at the specified follow-up, not the rate of infection or the prevention of disease.

The registry record describes participants with three prior vaccine doses and a minimum interval of at least 6 months since their last dose. It does not report detailed age ranges, health eligibility criteria beyond healthy adults, or the distribution of participant characteristics by group. Those details would help readers judge how closely the study population represents other populations, but they cannot be inferred from the posted primary results.

The study also includes a no-vaccine control group in its arm descriptions. The primary result entries, however, give estimates for Bivalent Moderna and Novavax only. A primary antibody estimate for the control group is not reported in the registry record, so the posted primary results do not present all three described groups side by side.

3. Trial Design

This is a Phase 3 randomized, double-blinded, parallel-group trial sponsored by Murdoch Childrens Research Institute. The registry record lists an enrollment of 496 and gives the study status as active, not recruiting. The recorded study start date is 2023-02-28, and the primary completion date is 2024-10-13.

The two vaccine interventions are a bivalent Moderna mRNA vaccine, identified in the arm description as mRNA-1273.214, and the Novavax protein subunit vaccine. Both are described as fourth-dose boosters for people who had received three earlier COVID-19 vaccine doses, with the last dose at least 6 months before participation. The record also describes a control group of eligible participants who did not receive a COVID-19 vaccine. The posted primary antibody results give group estimates for the Moderna and Novavax arms; a corresponding primary result for the control group is not reported in the registry record.

Random allocation means that participants are assigned to groups by chance, a design intended to limit systematic differences between groups. Double masking indicates that the trial is described as double-blinded, but the registry record does not specify which people were masked or how masking was maintained. A parallel design means participants are assigned to a group and assessed in that group rather than being described as crossing between interventions.

The primary endpoint is SARS-CoV-2 specific IgG antibodies at 28 days after booster vaccination. Serum samples were evaluated using the commercial Euroimmun S1 IgG ELISA, with results expressed as binding antibody units per millilitre and summarized as geometric mean concentrations with 95% confidence intervals. The registry record lists several secondary antibody, cellular immune-response and adverse-event outcomes, including measurements at later follow-up times. It does not report the detailed allocation procedure, masking procedures, protocol deviations, or a statistical analysis plan.

The enrollment figure is a registry entry, while the arm-specific primary results have their own reported participant counts. These quantities serve different purposes and should not be treated as interchangeable. The record does not explain the difference between planned enrollment and the counts contributing to the posted primary estimates.

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.

Baseline

Reasons for not completing this period:

28 Days

Reasons for not completing this period:

6 Months

Reasons for not completing this period:

12 Months

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Moderna group:By day 28 1 participant was lost to follow-up and 1 had withdrawn Novavax: 4 people missed their visit for the day 28 blood draw and 1 was a withdrawal.

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 SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination, measured over 28-days post booster vaccination.

The primary endpoint is the concentration of SARS-CoV-2 specific immunoglobulin G antibodies in serum at 28 days after booster vaccination. The assay is identified as the commercial Euroimmun S1 IgG ELISA, and the measurement unit is binding antibody units (BAU/mL). The registry reports the endpoint as a geometric mean concentration, together with a 95% confidence interval, for each intervention group.

Antibody concentration is an immunogenicity measure: it describes the immune response measured in blood after vaccination. A geometric mean is used for measurements that are commonly analyzed on a multiplicative scale and may be unevenly distributed, with some values much larger than others. It summarizes the typical level on that scale while limiting the influence of extreme values compared with an arithmetic average. This is a general statistical explanation of the measure, not an additional finding from the trial.

The endpoint is useful for comparing the measured antibody response between groups, provided a suitable direct comparison is reported. The registry record gives group-specific estimates, but does not report a confidence interval or formal test for the difference between groups in the primary result entries. A group-level estimate alone does not establish the precision of a between-group contrast.

This endpoint is not a direct measure of symptomatic infection, severe disease, or transmission. The registry record does not report that the antibody measure was used as a validated surrogate for those clinical outcomes. The primary result should therefore be interpreted as a laboratory immunogenicity result at the stated time point, rather than as evidence of clinical protection.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Why report a geometric mean?

Antibody concentrations can vary over a wide range and may be skewed rather than distributed symmetrically. In general, a geometric mean is calculated by transforming measurements to a logarithmic scale, averaging on that scale, and transforming back. This approach makes multiplicative differences more natural to describe and reduces the leverage of unusually high measurements compared with an arithmetic mean. The registry identifies the primary summary as a geometric mean concentration, but does not report the detailed calculation procedure or any transformations used in the analysis.

The geometric mean is a group summary, not a statement that every participant had a concentration close to the reported value. Individual observations may vary around the summary. The registry record does not provide individual-level measurements or a measure of participant-to-participant dispersion for the primary endpoint, so the posted group estimate cannot describe that full distribution.

What does the confidence interval communicate?

A confidence interval expresses sampling uncertainty around an estimated quantity under the assumptions of the method used. A narrower interval generally indicates greater precision for that estimate, while a wider interval indicates less precision. The primary endpoint uses 95% confidence intervals for the group-specific geometric means. These intervals do not quantify all sources of uncertainty, such as assay limitations, selection into the study, or departures from the analysis assumptions.

It is important to distinguish uncertainty around each group mean from uncertainty around a difference between groups. A formal comparison would ordinarily estimate a contrast and its uncertainty directly, using a method suited to the endpoint and study design. Separate confidence intervals do not supply that contrast, and the registry record does not report a primary between-group estimate or test. No comparative p-value should be inferred from the two group summaries.

How does randomization relate to interpretation?

Random allocation is intended to make treatment groups comparable on average with respect to measured and unmeasured characteristics at the time of assignment. It does not guarantee identical groups, particularly in any particular realized trial. Masking may help reduce behavior or assessment differences related to knowing the assigned intervention, but the registry record does not detail who was masked or how the procedure operated. Statistical methods and complete follow-up remain important even in randomized, double-blinded studies.

The parallel-group structure means that each participant is assessed in an assigned group. The primary antibody result is consequently presented as a group-specific concentration at the stated follow-up. The registry does not give a detailed model specification, adjustment variables, or a method for accounting for any departures from the intended design.

What is the role of the sample-size illustration?

The planning illustration is based on an observed effect and uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects defined as stated fractions of the observed effect. These are planning assumptions, not a description of the trial’s original design rationale. The registry record does not report the protocol’s sample-size justification, the effect size used in the original planning, or whether the trial had any prespecified interim analyses.

Sample-size calculations estimate how many participants per arm might be needed under stated assumptions to detect a specified effect with a chosen power. Such values are planning illustrations, not observed power and not evidence that a study has or has not demonstrated an effect. Their interpretation depends on the assumptions, including the anticipated variability and effect size. The record does not report the original assumptions needed to verify whether the trial’s enrollment target was based on the primary endpoint.

A recalculation from posted summaries, when one is available, is an unadjusted analysis and may not reproduce the sponsor’s prespecified method. In this record, the discrepancy indicator is false. For another endpoint, a two-arm recalculation was not available because values were missing or not estimable. Neither planning illustrations nor unadjusted recalculations should be confused with the trial’s own prespecified analysis.

What can the posted estimates establish?

The posted primary summaries establish the reported group-specific antibody geometric means and their confidence intervals at the specified follow-up. They do not provide the data needed to independently assess distributional assumptions, outliers, missing-data handling, or the exact estimation procedure. General statistical interpretation can explain what a geometric mean and interval represent, but it cannot fill in unreported analysis details.

The registry also lists immunologic outcomes involving neutralizing antibodies and cellular responses. These endpoints may use different assays, scales, and analysis methods. Results from different outcome families are not automatically comparable simply because they concern immune response. The record does not provide a complete statistical plan explaining how the outcomes were prioritized or analyzed together.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary antibody outcome alongside secondary outcomes covering SARS-CoV-2 specific IgG, neutralizing antibodies, interferon gamma, cytokine-expressing T cells, cytokine concentrations, and unsolicited adverse events. It reports 13 outcome measures and 10 posted secondary results. When several outcomes or time points are examined, the chance of at least one apparently notable result can increase. Statistical approaches for addressing multiple comparisons may include prioritizing a primary endpoint, adjusting significance thresholds, or treating secondary analyses as exploratory. The method used for this trial is not reported in the registry record.

The registry record does not report whether an adjustment for multiplicity was planned, how secondary outcomes were prioritized, or whether results at multiple follow-up times were analyzed under a prespecified testing sequence. The number of outcomes alone does not reveal whether an adjustment was appropriate or applied; that requires the analysis plan and the intended interpretation of each outcome.

For the primary outcome, the population notes state that in the Moderna group one participant was lost to follow-up and one had withdrawn by day 28. In the Novavax group, four people missed the day-28 blood draw and one was a withdrawal. The posted primary estimates have their own reported participant counts. The record does not explain whether missing measurements were excluded, imputed, or handled by another method, and it does not provide a detailed flow of participants through the analysis.

The record does not specify an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. It also does not report whether sensitivity analyses assessed the effect of missing data. Without those details, readers cannot fully evaluate whether the estimates could be affected by differences in follow-up or by the assumptions used to handle absent measurements.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bradyarrhythmia (0.7%), diverticulitis (0.7%), fall (0.7%), hand tendon injury (0.7%), infectious mononucleosis (0.7%).

The registry reports serious adverse-event counts and numbers at risk for the Moderna, Novavax, and control groups. The serious-event counts are 5 among 177 at risk in the Moderna group, 8 among 176 at risk in the Novavax group, and 8 among 143 at risk in the control group. No deaths are reported for any of these groups. These are counts as recorded in the registry; they do not by themselves establish that an event was caused by an intervention.

The record also lists serious-event terms, including bradyarrhythmia, diverticulitis, fall, hand tendon injury, infectious mononucleosis, and infective exacerbation of asthma. Each term is listed with 0.7%. The registry entry does not clarify in this summary how those terms map to treatment groups, so they should not be attributed to a particular group on the basis of this information alone.

Other adverse-event counts are reported as 10 among 177 at risk in the Moderna group, 8 among 176 at risk in the Novavax group, and 1 among 143 at risk in the control group. The registry record does not provide sufficient detail in these figures to characterize event severity, timing, duration, or relatedness. Counts across groups should be read as descriptive safety reporting rather than as a formal comparative safety analysis. The posted figures do not include a reported statistical comparison or an adjustment for differences in follow-up.

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

The primary result describes SARS-CoV-2 specific IgG antibody geometric mean concentrations at 28 days after booster vaccination in the Moderna and Novavax groups. The Moderna estimate is numerically higher than the Novavax estimate, and both are accompanied by group-specific 95% confidence intervals. These registry entries describe the posted antibody measurements; they do not on their own establish a treatment effect or a clinically meaningful difference.

The registry record does not report a direct comparison estimate, its confidence interval, or a formal test for the primary endpoint. Without such a comparison, the numerical difference between group summaries should not be treated as a quantified causal contrast. The record also does not provide a primary antibody result for the no-vaccine control group, despite describing that group in the trial arms.

An antibody concentration is a laboratory measure of immune response. It is not itself a count of infections, hospitalizations, or other clinical events. The primary result therefore does not show whether either vaccine reduced COVID-19 illness, how the measured antibodies relate to clinical protection, or how long any response persisted. The registry record does not report a validated threshold for interpreting the antibody concentrations as a particular level of protection.

The record includes safety outcomes and secondary immune-response outcomes, but the primary antibody summary cannot answer all of those questions. The serious adverse-event counts are descriptive, and the registry does not give a comparative safety analysis in the material reported for these results. Secondary outcomes include later antibody assessments and cellular measures, but those should be interpreted according to their own assays, time points, and analysis methods.

Accordingly, the result is best understood as a report of group-level immunogenicity at a specified follow-up, with uncertainty represented by confidence intervals. It is not a substitute for a direct statistical comparison, a complete safety assessment, or evidence about clinical outcomes. The registry does not report enough analysis detail to resolve those broader questions.

13. Why This Trial Matters Statistically

This trial is statistically notable because it places two different vaccine platforms within a randomized, double-blinded, parallel-group design and reports an immunogenicity endpoint as a geometric mean with confidence intervals. The design can support a structured comparison, while the reporting format makes clear that antibody concentrations are summarized on a scale appropriate to their measurement characteristics.

The distinction between group summaries and a direct comparison is especially important. Readers can see the estimated antibody concentration in each intervention group and the uncertainty around each estimate, but the registry record does not report a contrast between groups. Comparative interpretation requires an estimate of that contrast and its uncertainty, not only separate summaries. This is a general principle that applies to many randomized trials.

The trial also illustrates why the analysis population and missing-data methods matter. The registry notes participants who missed the day-28 blood draw or withdrew, but it does not describe the analysis handling. A transparent account of exclusions, missingness, and sensitivity analyses would help readers assess the robustness of the antibody estimates.

Multiplicity is another statistical consideration because the record lists a broad set of immune and safety outcomes. A clear hierarchy and analysis plan help distinguish confirmatory results from exploratory ones. The registry record does not describe such a plan, so readers should avoid treating every secondary result as if it had the same evidential status as the primary endpoint.

Finally, the described no-vaccine control arm is not represented in the posted primary antibody estimates. That gap limits the scope of the primary results as recorded. Together, these features make the trial a useful example of how design, endpoint choice, uncertainty, missing data, and completeness of reporting shape the interpretation of clinical research.

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 a primary antibody estimate for the no-vaccine control group, although a control group is described in the arm information. The posted primary results therefore cover the two vaccine groups rather than all described groups. The record also does not report a direct between-group estimate, confidence interval for a contrast, or primary hypothesis test.

Several details needed to assess the analysis are not reported in the registry record. These include the formal analysis population, the method used to handle missing antibody measurements, the statistical model or estimation procedure, any covariate adjustment, and the multiplicity strategy. The outcome notes document missed visits and withdrawals, but do not explain how these cases were treated in the estimates.

The record does not include detailed participant characteristics, such as age distribution or other baseline characteristics, that would help readers judge the composition of the groups and the applicability of results to other populations. It also does not provide individual-level antibody values or a description of variability beyond the confidence intervals for the geometric means.

The primary endpoint is a laboratory antibody measure at a single stated time point. Although later antibody and cellular outcomes are listed among the secondary measures, those are separate outcomes and do not change what the primary estimate measures. The registry record does not establish how the antibody result relates to clinical outcomes, nor does it report a validated protective threshold.

Finally, the record describes a sample-size planning illustration based on observed effects but does not report the original trial-design justification. It does not report interim analysis plans or a complete statistical analysis plan. These omissions restrict independent assessment of the design assumptions and the confirmatory status of results beyond the stated primary endpoint.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: COVID-19 Booster Study in Healthy Adults in Australia — NCT05658523.
• Registry record last updated 2026-01-02; status last verified 2025-07.
• Results first posted 2026-01-02.
• 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

NCT05658523 is a Phase 3 randomized, double-blinded, parallel-group study sponsored by Murdoch Childrens Research Institute. It evaluates a bivalent Moderna mRNA vaccine and a Novavax protein subunit vaccine as fourth doses in healthy adults in Australia who had previously received three COVID-19 vaccine doses. The record also describes a control group that received no COVID-19 vaccine.

The primary endpoint is SARS-CoV-2 specific IgG antibody concentration in serum at 28 days after booster vaccination, measured using the Euroimmun S1 IgG ELISA and summarized as a geometric mean in BAU/mL with a 95% confidence interval. The posted primary estimates are 6792.0 for Moderna and 3179.0 for Novavax; a primary control estimate and a formal between-group comparison are not reported in the registry record.

The registry lists secondary antibody, cellular immune-response, and adverse-event outcomes. It does not report the detailed analysis plan, multiplicity approach, analysis populations, or handling of missing primary endpoint measurements.