Pilot Study in Young Adults to Examine the Kinetics of Changes in the B-cell Repertoire Following TIV Immunization: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study in Young Adults to Examine the Kinetics of Changes in the B-cell Repertoire Following TIV Immunization (NCT02987374), a na phase 4 study. The primary outcome is Number of Participants Who Received Influenza Vaccine.

2. Clinical Question

The registry describes a pilot study of healthy young adults receiving the 2011-2012 Fluzone IIV3 vaccine. Its stated purpose was to investigate B-cell responses to trivalent influenza vaccine by obtaining blood samples at designated time points before and after vaccination. The primary outcome, however, is the number of participants who received the vaccine, rather than a numerical measure of B-cell repertoire change. The registry record does not report detailed results for B-cell measurements or the timing and values of individual biological outcomes.

These details define a descriptive question about vaccine receipt, not a comparative question about differences between treatments. Blood sampling before and after vaccination is part of the study purpose, but the registry does not report the biological outcome values needed to characterize the pattern or size of any changes. The stated secondary outcome concerns participants with related adverse events. The registry record does not give a detailed account of how relatedness was assessed or how the biological outcomes were analyzed.

3. Trial Design

This is a completed Phase 4 pilot study registered as NCT02987374. Stanford University is listed as the sponsor. The record gives a start date of 2012-05 and a primary completion date of 2012-12. The study is described as a single-group model, with allocation listed as NA and masking listed as none. Accordingly, the record does not describe a randomized treatment comparison or a masked comparison between groups.

The intervention is 2011-2012 Fluzone IIV3 (IM), identified in the arm description as seasonal trivalent flu vaccine. The brief summary says participants were vaccinated and had blood samples obtained at designated time points before and after vaccination. The registry does not report the exact sampling schedule, laboratory procedures, or the detailed measures used to characterize the B-cell repertoire. Those elements therefore cannot be reconstructed from the record.

The registry lists an enrollment of 10, and the primary outcome description states that 10 participants received the vaccine. These figures describe the registered enrollment and reported receipt; they should not be expanded into claims about additional analysis populations or completeness of follow-up. The record does not report participant flow, withdrawals, exclusions, or the number contributing data to each biological measure.

The primary outcome is a count of participants who received influenza vaccine, with a stated timeframe of Day 0 to 180 post-immunization. The listed secondary outcome is the number of participants with related adverse events. The record lists 3 outcome measures but provides no posted analyses. Sample-size illustrations based on an observed effect are not part of the study’s documented design justification; that justification is not reported in the registry record. The record also does not describe interim analyses or a detailed statistical analysis plan.

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: 10 participants received the 2011-2012 Fluzone IIV3 vaccine

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: Participants between the ages of 18-30

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Received Influenza Vaccine, measured over Day 0 to 180 post-immunization.

The primary endpoint is the number of participants who received influenza vaccine. It is a count outcome, with the unit stated as participants, and its timeframe is Day 0 to 180 post-immunization. The outcome description says that 10 participants received the 2011-2012 Fluzone IIV3 vaccine. This measure documents vaccine receipt in the enrolled study group.

As a descriptive endpoint, a receipt count can establish how many participants are recorded as having received the intervention. It does not measure the magnitude, timing, or diversity of a B-cell response. It also does not compare vaccine receipt with receipt under another intervention, because the study is registered as a single-group study without a comparator. The endpoint therefore answers a narrower question than the study’s stated biological purpose.

In general, an endpoint should correspond to the question researchers intend to answer. A count of participants receiving an intervention is useful for describing delivery or participation, while laboratory measures would be needed to describe biological response. The registry record does not report the detailed biological endpoint definitions, values, or analysis results needed to explain how B-cell repertoire changes were measured. The stated timeframe alone does not establish that every participant contributed measurements at every planned time point.

The distinction matters when interpreting the posted result. The reported count supports a statement about recorded vaccine receipt. It cannot by itself establish the timing or extent of biological changes, nor can it establish a causal contrast with an untreated or alternative-treatment group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a single-group pilot study and lists no analyses. The statistical concepts below are general explanations of how such data could be understood; they are not claims about methods used in this study. The actual analysis plan, laboratory analysis procedures, and any inferential model are not reported in the registry record.

What does a count endpoint tell the reader?

A count endpoint records how many participants meet a defined condition. Here, the condition is receipt of the influenza vaccine, and the reported count is 10 participants. A count can be useful for describing what occurred in the registered study group. By itself, it does not quantify the probability of an outcome in a broader population, establish a treatment effect, or measure biological change. To interpret a count as a rate or proportion, its denominator and the definition of the population being counted must be clear. The endpoint description gives a count and states that 10 participants received vaccine; it does not provide an inferential analysis.

What would a comparison require?

In general, a comparative treatment effect requires a clearly defined contrast between groups or conditions. This record describes a single-group model and allocation as NA, so it does not provide a concurrent control-group contrast. Measurements before and after vaccination can describe within-participant patterns if repeated values are collected and analyzed, but a before-and-after pattern alone does not separate the effect of vaccination from other influences that change over time. The registry record does not report the numerical repeated measurements or an analysis of them.

How are repeated biological measurements interpreted?

For general explanation, repeated observations from the same participant are related rather than independent. Statistical methods for repeated data account for that dependence and can describe trajectories, average changes, or variation among participants. Their suitability depends on the outcome scale, the timing of measurement, missing observations, and the scientific estimand. The record states that blood samples were obtained at designated times before and after vaccination, but the exact schedule, measured variables, and analytical approach are not reported. It is therefore not possible to identify whether the posted analyses used a repeated-measures model, participant-level summaries, or another approach.

Biological measurements can also have distributions that are skewed or more variable than a simple model assumes. In general, over-dispersion means that observed variability exceeds what a chosen model expects; ignoring it can make uncertainty estimates too narrow. This is a general consideration, not a finding about this study. The registry does not report the outcome distributions or model diagnostics needed to assess it.

What do uncertainty measures contribute?

In general, an estimate describes the value calculated from observed data, while a confidence interval conveys the range of values reasonably compatible with the data and the model’s assumptions. A narrower interval indicates greater precision under those assumptions, but does not remove bias or design limitations. A p-value is tied to a particular null hypothesis and model. It does not state the probability that a hypothesis is true, nor does it measure the size or importance of an effect. The record does not report confidence intervals, p-values, or estimates of B-cell change.

For a single-group count such as vaccine receipt, uncertainty could be assessed only after specifying a target population, statistical model, and assumptions. Even then, a precision interval would not create a treatment comparison where none exists. Because the registry provides no analysis for this endpoint, no interval or inferential conclusion should be inferred from the count alone.

What are the planning illustrations?

General sample-size illustrations translate an assumed effect and design into a hypothetical number of participants needed for a specified power under stated assumptions. The registry’s planning description says that its illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It also distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. These are planning conventions, not evidence that this single-group pilot used a two-arm design, and they are not observed power. A sample-size calculation cannot demonstrate that the study had a particular probability of detecting an effect after the data were collected.

The record does not report a design-based sample-size justification or the assumptions used to plan enrollment. No numerical planning outputs are stated in the registry record. Without those outputs and their assumptions, there is no basis for characterizing the study as adequately or inadequately powered for a particular biological outcome. In any case, power is tied to a defined outcome, effect, design, and analysis, none of which is detailed for the B-cell outcomes in the posted record.

Finally, multiplicity can arise when several outcomes, time points, or comparisons are examined. In general, testing many hypotheses can increase the chance of at least one apparently unusual result under a collection of null hypotheses. Methods to address this depend on the analysis goals and should be specified in advance. The registry lists 3 outcome measures and 0 analyses, but does not report a multiplicity strategy. Consequently, no adjustment method or family of tested hypotheses can be attributed to this study.

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("2011-2012 Fluzone IIV3 (IM)")
n      <- c(10)
events <- c(10)
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  2011-2012 Fluzone IIV3 (IM)  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 0 analyses. It identifies vaccine receipt as the primary outcome and lists the number of participants with related adverse events as a secondary outcome. The biological aims described in the brief summary are not accompanied by detailed numerical outcome results or analysis descriptions. The registry record does not report a prespecified hierarchy of additional outcomes, a multiplicity adjustment, or how any collection of time points or biological measures was handled.

In general, multiplicity is a concern when several hypotheses are evaluated. Without a stated plan, readers cannot determine whether reported inferential results, if any, were intended as confirmatory or exploratory, or how the chance of false-positive findings was considered. Since no analyses are listed, there are no posted hypothesis tests to interpret or adjustment procedures to assess.

Missing-data handling is also not reported in the registry record. The record does not state whether participants missed blood draws, whether outcomes were unavailable, or whether any imputation or other missing-data method was used. The statement that 10 participants received the vaccine does not establish that all measurements were available for every participant or time point.

Analysis populations are not described beyond the primary outcome’s statement about 10 vaccine recipients. The registry does not specify whether analyses were planned for all enrolled participants, only participants with available measurements, or another defined population. These details matter because exclusions and incomplete follow-up can affect both the interpretation and representativeness of results. No assumptions about missingness, participant exclusions, or analysis populations can be made from the posted record.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety listing reports 0 participants with serious adverse events among 10 at risk in the 2011-2012 Fluzone IIV3 (IM) group. It also reports 3 participants in the other adverse event category among 10 at risk. These are participant counts, not counts of individual event episodes, and the registry record does not provide detailed event terms in the serious category.

The listed secondary outcome concerns participants with related adverse events, but the record does not explain the criteria for judging relatedness or provide event-level descriptions. The death count is not reported in the registry record; a blank or unreported value should not be interpreted as a stated count of zero. The follow-up details for each safety outcome are not reported beyond the outcome information in the record.

In general, a count of zero serious events in a small study is a description of what was recorded in that study, not proof that an event cannot occur. A single-group listing also cannot establish whether an event count differs from what would occur without vaccination or under another intervention. The safety figures should therefore be read as descriptive observations within the registered group, with limited information about event definitions, timing, attribution, and completeness.

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

The posted record establishes that this completed pilot study enrolled 10 participants and states that 10 received the 2011-2012 Fluzone IIV3 vaccine. It describes a single-group study of healthy young adults, with blood sampling planned before and after vaccination. The safety listing reports 0 participants with serious adverse events and 3 in the other adverse event category, among 10 at risk for each category. These statements describe the registry’s recorded results.

Those results do not show the size or direction of a B-cell repertoire change. The study’s stated scientific purpose concerns B-cell responses and their kinetics, but the registry does not report the detailed biological measurements, outcome values, or analyses needed to characterize those responses. The primary endpoint counts vaccine receipt; it is not an immunologic endpoint.

The record also does not establish a causal effect of vaccination. It describes no comparator group, and allocation is listed as NA. A single-group observation cannot directly estimate how outcomes would have differed under another intervention or without vaccination. The record does not report confidence intervals, p-values, or a statistical model for the primary outcome or biological measures.

In general, a pilot study can be useful for exploring procedures and generating questions, but a descriptive result should not be treated as a definitive estimate of an effect. The registry does not report the study’s formal objectives for feasibility, any decision criteria, or a sample-size justification, so the intended role of the pilot beyond its stated biological purpose cannot be specified further.

The record is therefore informative about the registered design, intervention, vaccine receipt, and listed adverse-event counts. It is not sufficient to determine whether B-cell repertoire measures changed, how precisely any such changes were estimated, or how those changes compare with another group. Those questions require outcome details and analyses that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why the choice of endpoint matters when interpreting a clinical registry. The stated purpose is to investigate B-cell responses following trivalent influenza immunization, while the listed primary outcome counts participants who received the vaccine. Both pieces of information are relevant, but they answer different questions. Receipt documents exposure to the intervention; it does not quantify a biological response.

The single-group structure also sets an important boundary on statistical interpretation. Without a comparator group, the record can describe observations among vaccine recipients but cannot provide a randomized contrast. Blood samples before and after vaccination may support investigation of within-participant patterns, but the registry does not report the measurements or analyses needed to evaluate those patterns. The distinction between observing a change and attributing a change to an intervention is central to clinical research.

The record also shows why statistical precision cannot be inferred from enrollment alone. A count can be reported without an accompanying interval or model-based uncertainty estimate. For biological outcomes, interpretation would additionally depend on how measurements were defined, when samples were collected, whether observations were complete, and how repeated measurements were analyzed. Those details are not reported in the registry record.

Finally, safety counts and biological outcomes serve different roles. The listed adverse-event counts are descriptive and do not establish comparative safety. The absence of posted analyses means that the registry supports a limited statistical reading rather than a conclusion about efficacy or causal effects. Recognizing these boundaries helps readers distinguish what the record documents from questions that remain unanswered.

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.

This record has several limitations for interpretation of the study’s stated biological aim. It describes a single-group model, with allocation listed as NA and masking listed as none. There is no comparator group in the registered design, so the record does not support a direct treatment contrast. The sample is described as healthy young adults, which also limits how far observations might be generalized to populations not described in the registry.

The primary outcome is vaccine receipt rather than a measure of B-cell repertoire change. Although the study summary describes blood sampling before and after vaccination, the registry record does not report the exact sampling schedule, laboratory methods, detailed biological outcome definitions, or numerical B-cell results. It is therefore not possible to assess the magnitude, variability, or timing of biological responses from the posted information.

The registry lists 0 analyses. It does not report an analysis plan, uncertainty estimates, missing-data procedures, or analysis populations for the biological outcomes. The record also does not explain whether all planned samples were collected or whether participant follow-up was complete. These omissions prevent an assessment of the precision and completeness of any biological findings.

The safety listing is similarly limited: it gives participant counts but does not report detailed event terms, event timing, attribution criteria, or a death count. The registry does not report a formal sample-size justification. These limitations apply to what can be concluded from the registry record; they do not establish what was or was not performed outside the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study in Young Adults to Examine the Kinetics of Changes in the B-cell Repertoire Following TIV Immunization — NCT02987374.
• Registry record last updated 2017-04-21; status last verified 2017-04.
• Results first posted 2016-12-26.
• 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

NCT02987374 is a completed Phase 4 pilot study sponsored by Stanford University. The registry gives a start date of 2012-05 and a primary completion date of 2012-12. The study concerns healthy young adults receiving the 2011-2012 Fluzone IIV3 (IM) vaccine, with blood sampling described before and after immunization.

The design is listed as single group, with allocation NA and masking none. The primary outcome is the number of participants who received influenza vaccine during Day 0 to 180 post-immunization; the record states that 10 participants received the vaccine. The secondary outcome concerns participants with related adverse events. The safety listing reports 0 participants with serious adverse events and 3 in the other adverse event category, among 10 at risk for each.

The record lists 3 outcome measures and 0 analyses. Detailed B-cell outcome results, statistical methods, missing-data handling, and analysis populations are not reported in the registry record.