Booster Dose Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Booster Dose Trial (NCT05016622), a na phase 2 study. The primary outcome is Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study sponsored by Montefiore Medical Center. The registry lists an enrollment of 106 and the BNT162b2 vaccine as the intervention. The study began on 2021-08-10, had a primary completion date of 2022-04-20, and its status is terminated. The reason for termination is not reported in the registry record.

The registry lists no masking and no randomized allocation. With no concurrent control group, the design can describe antibody outcomes and adverse events among participants who received the booster, but it cannot directly estimate how those outcomes would differ without the booster or under another intervention. The primary result is specifically about the subgroup of 35 patients who were seronegative after the initial 2 dose vaccination series, rather than all 106 enrolled patients.

The primary outcome was assessed four weeks after administration of the first booster dose. Other listed outcomes concern antibody titers, seropositive status, neutralizing antibodies, and T-cell response. The registry includes no arm description beyond “Booster dose.” Eligibility details beyond the cancer diagnosis and lack of an antibody response after primary vaccination, the booster schedule beyond the stated first dose, and the reason for the terminated status are not reported in the registry record.

The study is not a randomized comparison, and its results should be read as observations from a treated group. Design details such as a prespecified sample-size justification, interim analyses, and a full statistical analysis plan are not reported in the registry record.

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: 189 patients were assessed for eligibility to receive a booster COVID-19 vaccine after at least 28 days following completion of the standard COVID-19 vaccination series. Of the 189 patients, 56 patients declined to participate in the study, 2 patients did not meet eligibility criteria, and 25 participants were not enrolled due to 'Other reasons.' Accordingly, 106 patients were enrolled into the Booster Dose Trial.

1st Booster: 4 Week Follow up Visit

1st Booster: 4-6 Month Follow up Visit

Reasons for not completing this period:

2nd Booster: 4 Week Follow up Visit

Reasons for not completing this period:

2nd Booster: 4-6 Month Follow up Visit

Analysis population for the primary outcome, as defined in the registry: 35 of 106 patients were seronegative after initial 2 dose vaccination series. At 4 weeks following receipt of the booster vaccine, 57% (20/35) of these patients seroconverted and had a detectable antibody response as demonstrated by anti-S antibody testing

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: 106 participants were enrolled into the study.

6. Primary Endpoint

The registry lists the primary outcome as Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations, measured over 4 weeks after administration of 1st booster dose.

The primary endpoint is the rate of seroconversion for SARS-CoV-2 Spike antibody among patients who were seronegative after their primary series of COVID-19 vaccinations. The registry defines the outcome as a percentage of patients demonstrating booster-induced seroconversion, assessed by anti-Spike antibody testing. Its timeframe is four weeks after administration of the first booster dose.

The registry states that 35 of 106 patients were seronegative after their initial 2 dose vaccination series. Of these, 57% (20/35) had seroconverted and had a detectable antibody response at the four-week assessment. The numerator represents participants with the reported response; the denominator is the seronegative subgroup identified after the primary series.

In general, a seroconversion endpoint provides a way to summarize whether a laboratory marker changes from an undetectable or negative state to a detectable or positive state. It is a measurable antibody outcome, rather than a direct measure of symptoms, hospitalization, or other clinical outcomes. Detectable antibody status alone does not establish the degree or duration of protection from infection. The registry record does not report a confidence interval for the endpoint or further details about the antibody assay threshold.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure: a participant either demonstrated the reported anti-Spike antibody response or did not. For a binary endpoint, the basic descriptive statistic is the proportion of participants with the event divided by the number assessed. The registry reports 20 participants with seroconversion among 35 who were seronegative after their primary vaccination series, expressed as 57% (20/35).

What does the proportion describe?

The proportion describes the observed frequency of seroconversion in the subgroup that met the endpoint’s starting condition: seronegativity after the primary series. It is not the proportion of the full enrollment of 106, and it is not a comparison of the post-booster result with a control group. The endpoint’s definition links the measured result to anti-Spike antibody testing, and the stated assessment time is four weeks after the first booster dose. A different assessment time or assay definition could yield a different measured proportion; further assay details are not reported in the registry record.

How should uncertainty be understood?

In general, an estimate from a sample is subject to sampling variability. A confidence interval communicates this uncertainty by giving a range of values compatible with the observed data under a chosen method and assumptions. It is not a guarantee that the true value lies in that range, nor does it address every source of bias. The registry record does not report a confidence interval for the primary endpoint, so the posted proportion is not accompanied by an interval estimate of precision.

For binary outcomes, statistical methods commonly use a binomial model, which treats each participant’s outcome as an event or no event. The appropriateness of a particular interval or test depends on the analysis plan and data structure. The registry record does not report the method used for an inferential analysis of this endpoint, and it lists 0 analysis records. No inferential method should therefore be attributed to the study on the basis of the posted primary result alone.

What can a single-group result establish?

In general, a single-group design can estimate an outcome frequency among participants who receive an intervention, subject to how the participants are selected, assessed, and followed. It does not directly estimate a treatment contrast because there is no concurrent comparison group. Randomization, when used, helps make treatment groups comparable with respect to measured and unmeasured characteristics on average; that feature is absent from the design described in the registry. Consequently, the reported seroconversion proportion is an observed outcome after boosting, not an estimate of the difference attributable to boosting.

Other possible influences on an antibody result include participant characteristics, timing of measurement, and laboratory measurement processes. These are general considerations, not claims that a specific source of bias occurred in this study. The registry record does not report enough detail to assess those influences or to determine how the analysis handled any variation in measurement or follow-up.

How does sample-size planning relate to the result?

In general, sample-size planning specifies assumptions about the effect to detect, significance level, allocation, and statistical method before data collection. The registry record does not report the trial’s own sample-size justification. A separate planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not describe this single-group trial’s design. Any resulting sample sizes are planning illustrations, not observed participant counts or evidence of observed power. The registry does not report an interim-analysis plan.

Over-dispersion is relevant in statistical models when observed variability exceeds what a chosen model expects; accounting for it can affect standard errors and interval estimates. This is a general concept and does not establish that over-dispersion applies to a binary participant-level endpoint in this study. No such analysis is described in the registry record.

Overall, the available methods information supports a straightforward reading of the posted primary proportion, but not a reconstruction of a full prespecified statistical analysis. Details about interval estimation, hypothesis testing, missing observations, analysis populations, and any adjusted analyses are not reported in the registry record.

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("1st Booster Dose")
n      <- c(35)
events <- c(20)
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  1st Booster Dose  35  20  57.1  39.4  73.7  40.9  72.0  40.8  72.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including positive anti-Spike IgG titer, spike antibody titer, changes in titers for hematologic and solid tumor malignancies, seropositive or seronegative status after the first booster, neutralizing antibodies among seropositive patients, and T-cell response among patients with a negative anti-S antibody. It also lists 38 outcome measures in total. Considering multiple outcomes can increase the chance of apparently notable findings arising by chance when many statistical tests are conducted.

In general, a trial may address multiplicity by identifying a primary outcome, specifying a testing hierarchy, adjusting significance thresholds, or emphasizing estimation over multiple significance tests. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or an adjustment method. It contains 0 analysis records, so no multiplicity-adjusted or unadjusted analyses of the listed outcomes can be identified from the record.

The registry reports the primary result as 57% (20/35), but does not report a confidence interval or an inferential test. It does not report results for the listed secondary outcomes. Their absence from the posted results should not be interpreted as evidence that no such measurements were collected or that their results were null.

Missing-data handling and analysis populations are also not reported in the registry record. The primary denominator is 35 seronegative patients, but the record does not explain whether every eligible participant completed the four-week assessment, how missing antibody measurements were handled, or whether any participants were excluded from the primary analysis. These omissions limit assessment of potential bias from incomplete follow-up. The registry does not describe imputation, sensitivity analyses, or a per-protocol or intention-to-treat analysis population.

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: fever (0.9%).

For the booster-dose group, the registry lists 106 participants at risk for serious adverse events and 1 affected, 106 at risk for other adverse events and 63 affected, and 0 deaths. These are safety counts in the registry; the record does not provide a comparison group that would support a comparative estimate of event risk.

The listed serious-event term is Fever at 0.9%. The registry does not report further context for that term in the registry record, such as the event’s timing, duration, clinical course, or whether it was judged related to vaccination. The term and percentage should not be interpreted as establishing causation. The other-adverse-event count is not a measure of severity, and the registry record does not provide a detailed account of the individual events in that category.

In general, adverse-event counts describe events observed and recorded during a study; they do not by themselves show whether an intervention caused those events. Judging comparative safety typically requires contextual information about event definitions, follow-up, background rates, and a suitable comparison. Those details are not reported in the registry record, so the counts should be read as descriptive safety information rather than as a causal or comparative assessment.

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

The result establishes what the registry reports for the primary endpoint: four weeks after the first booster dose, 57% (20/35) of the patients who had been seronegative after the primary series had a detectable anti-Spike antibody response. It provides a measured antibody outcome for this subgroup at the specified time point. The result does not describe the response among every enrolled participant, because the primary endpoint focuses on the subgroup of 35 seronegative patients.

The result does not establish how much the booster changed the probability of seroconversion compared with no booster or another intervention. The study was single-group, with no randomized allocation or comparator. It also does not establish the duration of antibody response, clinical protection, or changes in infection or disease outcomes. Antibody detection is a laboratory endpoint, and the registry’s primary result does not itself answer those broader questions.

Precision is not fully conveyed by the posted result because the registry record does not report a confidence interval or inferential test. The observed proportion should therefore be read as a point estimate from the assessed subgroup, not as a precisely bounded value or a guarantee about outcomes for other patients.

The study also lists outcomes involving antibody titers, neutralizing antibodies, and T-cell response, but results for these outcomes are not reported in the registry record. The safety counts are descriptive and do not establish causal relationships. Taken together, the record supports a narrow interpretation of the primary antibody finding and leaves important questions about comparison, durability, clinical outcomes, uncertainty, and other listed outcomes unresolved.

14. Why This Trial Matters Statistically

This trial illustrates how the endpoint and design determine the scope of a statistical conclusion. The primary result is an antibody response proportion in a defined subgroup: patients with cancer who were seronegative after their primary vaccination series. Keeping the denominator and assessment time visible is essential to avoid generalizing the finding to all enrolled patients or to a different time point.

The single-group structure makes a useful distinction between describing an observed response and estimating a treatment effect. A proportion after an intervention can be informative about outcomes in the treated group, but without a concurrent comparison it cannot show how outcomes would have differed under another condition. This distinction is central to interpreting many clinical studies, particularly when a laboratory marker is the primary endpoint.

The record also highlights why uncertainty and analysis details matter. The primary result is reported without a confidence interval or inferential test, and the registry lists multiple other outcome measures without analysis records. A clear account of analysis populations, missing data, and multiplicity would help readers understand how stable and selective the reported findings are. Those details are not reported in the registry record.

Finally, safety counts need the same careful framing as efficacy-related measurements. Counts can describe what was recorded, but a single-group study does not provide a direct comparative safety estimate. Reading the antibody result and adverse-event counts as descriptive evidence, while recognizing what they cannot establish, keeps the statistical interpretation aligned with the design.

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 principal limitation for interpretation is the absence of a comparator. The study’s single-group design cannot distinguish the observed antibody response following the booster from what might have occurred without the booster or with another intervention. No randomized allocation or masking is reported.

The primary endpoint concerns antibody detectability four weeks after the first booster dose. The registry record does not report later antibody measurements for this endpoint, so it does not establish how long the response persisted. It also does not report clinical outcomes such as infection or disease severity as the primary measure. A detectable antibody response should not be treated as equivalent to a demonstrated clinical benefit.

The estimate is reported as 57% (20/35), with no confidence interval or inferential test in the registry record. This limits the information available about statistical precision. The record does not explain missing-data handling, participant flow through the four-week assessment, or the analysis population beyond identifying the seronegative subgroup.

Further limitations include the absence of a reported sample-size justification, interim-analysis plan, and full statistical analysis plan. The registry lists 38 outcome measures and multiple secondary outcomes, but does not report their results or a multiplicity approach. Details about assay thresholds and other measurement procedures are also not reported in the registry record. The study status is terminated, but the reason is not reported; no conclusion about the circumstances of termination can be drawn from that status alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Booster Dose Trial — NCT05016622.
• Registry record last updated 2024-07-31; status last verified 2024-07.
• Results first posted 2024-07-31.
• 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 phase 2 study, sponsored by Montefiore Medical Center, evaluated a BNT162b2 booster in patients with cancer. The registry lists an enrollment of 106, a single-group design, no masking, and terminated status. The reason for termination is not reported in the registry record.

The primary endpoint was seroconversion four weeks after the first booster among patients who were seronegative after their primary series. The registry reports that 35 of 106 patients were seronegative after their initial 2 dose series, and 57% (20/35) had a detectable anti-Spike antibody response at four weeks.

The registry lists secondary antibody and T-cell outcomes, 38 outcome measures, and 0 analysis records. It does not report confidence intervals, a statistical analysis plan, missing-data procedures, or a multiplicity strategy. Safety listings include 1 serious adverse event, 63 other adverse events, and 0 deaths among 106 at risk for each category. These results are descriptive; the single-group design does not provide a randomized comparison.