COVID-19 VAX Booster Dosing in Patients With Hematologic Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for COVID-19 VAX Booster Dosing in Patients With Hematologic Malignancies (NCT05028374), a na phase 2 study. The primary outcome is Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion..

2. Clinical Question

3. Trial Design

This phase II study evaluated a single Moderna mRNA COVID-19 vaccine booster in patients with hematologic malignancies who had low antibody levels after a prior vaccination. The registry lists multiple myeloma, AL amyloidosis, and chronic lymphocytic leukemia among the conditions. The intervention was one 0.5 mL intramuscular dose, administered according to the manufacturer's package insert. The record describes the dose as the same across all enrollment cohorts.

The study is recorded as single-group, with allocation not applicable and no masking. Enrollment was 119. Although the adverse-event results are organized by Cohort 1, Cohort 2, and Cohort 3, the registry record does not report how participants were assigned to those cohorts or provide a randomized control group. The cohorts therefore should not be treated as randomized treatment arms or as a like-for-like comparison.

The primary outcome was antibody seroconversion from negative to positive, assessed 28 days (+/- 3 days) after the booster. A secondary outcome was the observed rate of a strong positive anti-SARS-CoV-2 antibody response. The registry record identifies two outcome measures but does not report the primary or secondary response results.

The study status is completed. The registry lists a start date of 2021-08-17 and a primary completion date of 2021-11-02. It does not report a detailed statistical analysis plan, cohort definitions, or the timing and conduct of any interim analyses. These details should not be inferred from the phase, status, or cohort labels.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants who received a single dose of the Moderna mRNA COVID-19 vaccine administered intramuscularly.

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 Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion., measured over 28 days (+/- 3 days) following a booster dose of the Moderna mRNA COVID-19 vaccine.

The primary endpoint was the observed response rate of anti-SARS-CoV-2 antibody seroconversion. The registry defines seroconversion as anti-SARS-CoV-2 IgG antibody changing from negative to positive. The measurement was scheduled 28 days (+/- 3 days) after a single Moderna mRNA COVID-19 vaccine booster. The endpoint population is described as participants who received that booster intramuscularly.

As a binary outcome, seroconversion distinguishes participants who meet the specified antibody-response definition from those who do not. In general, a response proportion can describe how common the defined response was among the participants assessed. It is not, by itself, a comparison with an untreated or randomized control group, nor does it establish how long an antibody response lasts. The registry record does not report the number assessed, the number who seroconverted, or the resulting response rate.

The registry also identifies a secondary outcome, the observed rate of a strong positive anti-SARS-CoV-2 antibody response. Its operational definition and numerical result are not reported in the registry record. Without the outcome counts and a clear account of assessment completeness, the magnitude and precision of either antibody response cannot be judged from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint represent?

The primary outcome is binary: each participant either meets the recorded definition of seroconversion or does not. In general, a response rate is a proportion formed from the number meeting that definition and the number assessed for it. Those counts need to be reported to understand what observations underlie the rate. The registry record defines the endpoint but does not report either count or the resulting rate.

The endpoint is also tied to a specific assessment window, 28 days (+/- 3 days) following the booster. In general, outcomes measured at a particular time describe status around that assessment, not necessarily response at other times. The registry record does not report longer-term antibody measurements, so persistence cannot be assessed from the stated primary endpoint.

What would a confidence interval tell readers?

In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. For a response proportion, it communicates uncertainty as well as the observed estimate. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. It does not guarantee that the true value lies within the interval, and it does not correct for bias, missing data, or an unsuitable study design.

No confidence interval for seroconversion is reported in the registry record. Without the response estimate and its uncertainty interval, readers cannot judge whether the result is precise or whether a range of materially different response levels remains compatible with the observations. A statistical test result alone, even if it had been reported, would not substitute for examining the size and precision of an estimate.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among participants who received an intervention. A randomized comparator can support a more direct estimate of how outcomes differ between assigned groups, subject to the trial's conduct and analysis. This study is recorded as single-group, with allocation not applicable and masking none. Thus, the listed cohorts should not be interpreted as randomized arms, and differences between cohort counts do not establish a treatment effect.

The seroconversion definition refers to a change from negative to positive, but the record does not report the baseline and follow-up assessment counts. It is therefore not possible to reconstruct the endpoint result or assess whether all participants with a baseline negative result had a follow-up measure. A change in antibody status after the intervention is not, on its own, a controlled estimate of what would have occurred without the intervention.

How should the planning assumptions be read?

The registry's planning assumptions describe an illustration based on the observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These assumptions do not match the recorded single-group design as a description of how this trial was conducted. They should be understood only as planning assumptions, not as evidence that the trial used a two-arm randomized design.

In general, a sample-size planning calculation estimates how many participants might be needed under chosen assumptions about an effect, variability, allocation, and statistical method. Such a calculation is not observed power, and it does not show that a study has or has not found an effect. Planning illustrations based on an observed effect are also dependent on that effect estimate, which may be uncertain. The registry record does not report the trial's own sample-size justification or a detailed statistical plan. No trial-specific calculation beyond the stated assumptions should be inferred.

For a binary response, analysis choices can include how to calculate the proportion and its uncertainty and how to handle participants without a follow-up measurement. In general, different reasonable methods may yield different intervals, especially when counts are small or outcomes are uncommon. The registry record does not report the method used for a primary response analysis, nor does it provide results with which to examine such choices.

Why do event counts need context?

Serious adverse events are reported by cohort as counts of participants affected and at risk. In general, counts and denominators should be read together: a count alone does not communicate the frequency in a cohort, and a frequency does not establish whether an event was caused by treatment. Comparisons also depend on consistent definitions, follow-up, and methods. The serious-event counts in the registry are descriptive; the record does not report a randomized safety contrast or causal attribution.

Over-dispersion is a general issue for count outcomes when the variability exceeds what a chosen model expects. It can make uncertainty estimates too small if the model assumes less variability than is present. The registry's primary endpoint, however, is a binary seroconversion outcome rather than a count rate over person-time, and the record does not report a count model or an over-dispersion assessment. No such analysis should be presumed.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1", "Cohort 2", "Cohort 3")
n      <- c(52, 50, 16)
events <- c(29, 28, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1  52  29  55.8  41.3  69.5  42.3  68.4  42.3  68.4
ARM  Cohort 2  50  28  56.0  41.3  70.0  42.3  68.8  42.2  68.9
ARM  Cohort 3  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary antibody-seroconversion outcome and a secondary strong-positive antibody-response outcome. Having more than one outcome raises a general question about multiplicity: if several hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the set of tests. The registry record does not report a multiplicity adjustment or a prespecified testing hierarchy. It also does not report inferential results for either outcome. No adjustment strategy should be assumed.

The registry records 0 analyses. This means the record does not provide a reported analysis for the identified outcomes; it does not establish whether analyses were or were not conducted outside the registry. The statistical analysis plan and any interim-analysis procedures are not reported in the registry record.

Missing outcome data can affect both the estimated response and its uncertainty. In general, interpretation depends on how many participants were eligible for assessment, how many had usable measurements, why measurements were missing, and how the analysis handled missingness. Those details are not reported for the primary endpoint. The record therefore does not establish whether the reported enrollment count corresponds to the primary endpoint analysis population, or whether any participants lacked the scheduled antibody assessment.

The endpoint population is described as participants who received a single booster dose, but the record does not give a complete analysis-population definition. It does not state how protocol deviations, incomplete follow-up, or other exclusions were handled. These omissions limit assessment of the relationship between enrollment, outcome ascertainment, and analysis. They also prevent evaluation of whether the endpoint results, if available elsewhere, represent all enrolled participants or a selected subset.

The record's planning assumptions include a significance level and allocation framework, but they are described as an illustration rather than the trial's own statistical plan. They do not answer how multiplicity, missing data, or analysis populations were handled in this study.

12. 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: hypercalcemia (6.2%).

The registry lists serious adverse events separately for Cohort 1, Cohort 2, and Cohort 3. The at-risk counts are 52, 50, and 16, respectively; the corresponding counts of participants affected by serious adverse events are 0, 0, and 1. These are descriptive counts within the cohorts. They are not a randomized comparison, and differences between cohorts cannot be interpreted as causal effects.

The registry lists hypercalcemia at 6.2% among the top serious adverse-event terms. It does not provide the event count associated with that term in the record, nor does it report further detail about timing, severity, recurrence, or attribution. The record also lists deaths by cohort: 6 in Cohort 1, 4 in Cohort 2, and 2 in Cohort 3. It does not report whether those deaths were considered related to the booster, so the counts should not be interpreted as treatment-caused deaths.

In general, safety counts are most informative when the event definitions, follow-up period, participant-level denominators, and attribution procedures are clear. The registry record does not provide all of that context. The reported figures describe what was recorded by cohort; they do not establish comparative risk or determine causation.

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

The registry record establishes that a phase II, single-group study evaluated a Moderna COVID-19 vaccine booster in patients with hematologic malignancies and low antibody levels after prior vaccination. It defines the primary outcome as anti-SARS-CoV-2 IgG seroconversion from negative to positive, measured 28 days (+/- 3 days) after the booster. These are useful details for understanding the intended question and the timing of assessment.

The record does not report the primary response count or rate, a confidence interval, or an analysis result. It also does not report the result for the secondary strong-positive antibody outcome. Therefore, the record cannot establish the observed level or precision of either antibody response. A completed study status is not a substitute for outcome results.

Even if a response estimate were available, a single-group observation would describe the participants assessed rather than provide a randomized estimate of the booster’s effect relative to a control. Seroconversion indicates a change in the specified antibody measure; it does not by itself establish clinical protection, duration of response, or an effect on illness. Those questions are not answered by the endpoint description.

The serious-event figures are also descriptive. The registry lists affected-participant counts by cohort and records deaths, but does not report attribution or provide a randomized safety comparison. These counts should not be read as proof that the booster caused an event, nor as evidence that it prevents or excludes one. The study description and safety counts alone cannot determine comparative safety.

Overall, the record gives the design, intervention, outcome definitions, and selected safety counts, but lacks the primary and secondary response estimates and analysis details needed to judge the antibody findings. Conclusions about the size, precision, or causal meaning of the primary result are not supported by the registry information reported.

14. Why This Trial Matters Statistically

This trial addresses a specific statistical question: whether an antibody response, defined as a change from negative to positive, was observed after a booster in patients with hematologic malignancies who had low antibody levels following prior vaccination. The registry defines a post-booster assessment window and identifies both a primary seroconversion outcome and a secondary strong-positive response outcome. Clear endpoint definitions and assessment timing are essential for interpreting a clinical study, even when numerical results are unavailable.

The design also illustrates an important distinction between describing outcomes and estimating comparative effects. A single-group study can record what happened among participants receiving the intervention, but without a randomized comparator it cannot isolate the intervention's effect from other explanations. The cohort labels in the safety record do not change that design. Readers should distinguish a within-study response description from a controlled treatment comparison.

Precision is another central issue. A response count or proportion is more informative when accompanied by an uncertainty estimate and a clear account of who was assessed. The registry record does not report primary response results, intervals, or missing-outcome handling. This absence prevents readers from evaluating both the magnitude of the response and the uncertainty around it.

The record's planning assumptions also highlight why design assumptions matter: an illustration based on two-arm equal allocation is not a description of a single-group trial. Keeping planning exercises separate from the observed design avoids treating hypothetical sample-size calculations as trial results or observed power.

Finally, the safety counts underscore the difference between event reporting and causal interpretation. Counts organized by cohort can describe recorded events, but causal attribution and comparative risk require context and an appropriate design. These statistical distinctions are relevant when reading registry records in which design details are available but outcome analyses are not.

15. 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 main limitation of the registry information is that it does not report the primary seroconversion count, response rate, or uncertainty estimate. The secondary strong-positive antibody result is also not reported. As a result, the intended antibody outcomes cannot be quantitatively assessed from the registry record, despite the study being marked completed.

The study is recorded as single-group, without masking and without a randomized comparator. Any observed antibody response would therefore be a descriptive finding among participants assessed, not a randomized estimate of the booster’s effect. The record does not explain how the three cohorts were defined or how participants entered them, so cohort labels should not be treated as an explanatory comparison.

Important outcome-assessment details are not reported in the registry record, including the number with usable antibody measurements, the handling of missing measurements, and the full analysis-population definition. The record also does not provide a detailed statistical analysis plan, a sample-size justification for the trial's own design, or information about interim analyses. It is not possible to determine from the record whether such details exist elsewhere or how they may have influenced analyses.

For safety, the record supplies cohort-specific serious-event and death counts but does not give the full context needed to evaluate attribution, follow-up, or comparisons. The reported counts do not establish cause. More generally, the listed conditions do not indicate how results might vary across disease types or other participant characteristics; subgroup results are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: COVID-19 VAX Booster Dosing in Patients With Hematologic Malignancies — NCT05028374.
• Registry record last updated 2023-12-20; status last verified 2023-11.
• Results first posted 2023-11-18.
• 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.

19. Record Summary

This completed phase II study evaluated one 0.5 mL intramuscular Moderna mRNA COVID-19 vaccine booster in patients with hematologic malignancies and low antibody levels after prior vaccination. Enrollment was 119. The registry records a single-group design, no masking, and no randomized comparator.

The primary endpoint was anti-SARS-CoV-2 IgG seroconversion from negative to positive, assessed 28 days (+/- 3 days) after the booster. A strong positive antibody response was listed as a secondary outcome. Neither outcome result is reported in the registry record, and 0 analyses are recorded.

Serious adverse events are listed by cohort, along with deaths; the record does not report causal attribution. The study start date is 2021-08-17 and the primary completion date is 2021-11-02. The record does not report a detailed analysis plan, handling of missing outcome data, or definitions for the cohorts.