The Human Mucosal Immune Responses to Influenza Virus (SLVP026): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Human Mucosal Immune Responses to Influenza Virus (SLVP026) (NCT03023553), a non-randomized phase 4 study. The primary outcome is Number of Participants From Each Arm Who Received Influenza Vaccine.

2. Clinical Question

3. Trial Design

This was a Phase 4, parallel-group study with non-randomized allocation and no masking. The registry describes enrollment of 13 participants and lists the study status as completed. The recorded start was 2012-12, and primary completion was 2013-02. Stanford University is listed as the sponsor.

The arm descriptions identify healthy adult males and females, 18-30 years of age. Participants in the TIV Group were to receive standard trivalent, inactivated influenza vaccine (TIV), Fluzone®. Participants in the LAIV Group were to receive intranasal live, attenuated influenza vaccine (LAIV), FluMist®. These descriptions establish the intended group interventions, but the registry record does not report the group assignment process beyond identifying allocation as non-randomized.

Non-randomized allocation matters when interpreting a comparison. Random allocation is one way to reduce systematic differences between groups at the start of a study; without it, differences in participant characteristics or other factors may be related to group assignment. The registry record does not report whether or how such differences were measured or adjusted for. The arm titled “TIV/ Control Group” still received a vaccine, so it should not be read as an untreated control arm.

The stated scientific focus was immune responses to seasonal influenza vaccine in single cells from nasal passages, compared with cells in circulating blood. The primary outcome registered in the results record, however, is the number of participants in each arm who received influenza vaccine during Day 0 to 28. Details such as participant flow, group sizes in the arm descriptions, laboratory procedures, and the 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.

Overall Study

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: In LAIV Group, 13 subjects initially consented. One subject was determined ineligible due to age. Twelve subjects completed the LAIV Group.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants From Each Arm Who Received Influenza Vaccine, measured over Day 0 to 28.

The primary endpoint is titled “Number of Participants From Each Arm Who Received Influenza Vaccine.” Its unit is participants, its measure type is a count, and its timeframe is Day 0 to 28. It is therefore an endpoint about whether participants received vaccine during the stated period, rather than a measurement of immune activity, vaccine response, or influenza illness.

In general, recording receipt of an intervention can describe whether participants were exposed to the treatment specified for their group. That can be relevant to understanding study implementation and interpreting outcomes that depend on receiving the intervention. A count alone does not describe the amount or quality of an immune response, establish a causal effect, or show whether one vaccine is preferable to another.

The registry record does not report the primary endpoint result or an analysis of it. It also does not report a definition of how vaccine receipt was verified or how participants with missing receipt information were handled. The study’s brief summary names nasal and circulating-blood immune responses as its scientific focus, but the primary registered endpoint does not itself quantify those responses. The number of participants with related adverse events is listed separately as a secondary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant count, and the adverse-event outcomes are also counts of participants affected. In statistical terms, an event outcome records whether an individual experienced a defined event during a specified observation period. A group-level count reports how many participants met that definition. Such counts are descriptive unless accompanied by an analysis that estimates uncertainty or compares groups.

For a binary event outcome, analysts may describe the number affected alongside the number whose event status was assessed. The number at risk in the registry’s safety entries supplies that denominator for those entries. A proportion can help compare groups when denominators and outcome definitions are clear, but no new proportion is needed to interpret the counts posted. The registry record does not report an inferential analysis of the adverse-event counts or an estimate of the difference between arms.

A confidence interval is a statistical range intended to convey uncertainty around an estimate under a specified method and assumptions. In general, intervals tend to be less precise when the amount of information is limited, and rare events can be especially difficult to estimate from small groups. The registry record does not report confidence intervals for the primary or safety outcomes. Therefore, the posted zero affected counts should not be read as precise estimates of the underlying event risk.

A p-value, when reported, describes how compatible data are with a specified statistical model or null hypothesis. It does not measure the probability that a treatment works, and it does not by itself convey the size or practical importance of an effect. No p-value or test result is reported in the registry record. With no reported primary-outcome result or group comparison, there is no basis for interpreting statistical significance for the registered primary question.

Randomization and masking are design features, not statistical tests. Random allocation can help balance measured and unmeasured participant characteristics across groups on average. In a non-randomized study, groups may differ for reasons associated with treatment choice or assignment, so a crude contrast may mix treatment effects with those other differences. Masking can reduce certain forms of expectation or assessment bias, depending on how it is used. This study is listed as having no masking. The registry record does not describe methods to address bias from non-random allocation or lack of masking.

The registry describes two arms in a parallel model: participants are assigned to one group rather than both groups being described as sequential periods for each participant. The record does not report group assignment procedures beyond non-randomized allocation, nor does it report group sizes in the arm descriptions. The safety entries list 3 participants at risk in the TIV/ Control Group and 8 in the LAIV Group; those safety denominators should not be assumed to answer every question about the analysis population.

The registry record describes a planning illustration based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration is a planning calculation, not evidence that a trial was designed or conducted with that sample size, and it is not observed power. A sample-size calculation depends on assumptions about the effect to detect and the chosen error rate. The record does not report the trial’s own sample-size justification, and no primary effect estimate is reported from which to interpret a planning illustration as evidence about this study’s findings.

Multiplicity refers to the increased chance of a false-positive result when many hypotheses or outcomes are tested. Statistical plans may designate a primary outcome, specify a limited set of comparisons, or adjust interpretation for multiple tests. The registry lists a primary outcome and a secondary adverse-event outcome, but it does not report a multiplicity strategy or a set of statistical tests. As no analyses are listed, the registry results do not allow assessment of how multiple outcomes or comparisons were handled.

Missing-data methods matter when outcome status is not known for every participant. Different assumptions about participants without recorded outcomes can affect estimates, especially if missingness is related to treatment or outcome. The registry record does not report missing-data counts, imputation methods, or sensitivity analyses. It also does not report defined analysis populations, such as whether analyses included everyone enrolled or only participants with recorded outcome information. These omissions limit assessment of how the observed counts relate to all enrolled participants.

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("TIV/ Control Group", "LAIV Group")
n      <- c(4, 9)
events <- c(3, 8)
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  TIV/ Control Group  4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7
ARM  LAIV Group  9  8  88.9  51.8  99.7  56.5  98.0  55.5  97.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary count of participants in each arm who received influenza vaccine and the secondary number of participants with related adverse events. It reports no analyses. A multiplicity plan, including how the outcomes or any comparisons were prioritized or adjusted, is not reported in the registry record. Without reported tests or estimates, it is not possible to evaluate the implications of testing multiple outcomes.

The record does not report how many participants had missing primary or secondary outcome information, how missing observations were handled, or whether any sensitivity analyses were conducted. It also does not define analysis populations or state whether the posted safety denominators correspond to all enrolled participants, participants who received vaccine, or another group. These details are important because conclusions from an analysis depend on who was included and how incomplete records were treated.

In general, a complete-case analysis uses only participants with recorded outcome information, while other approaches make assumptions to incorporate missing data. Neither approach can be attributed to this study from the registry entry. The posted safety counts should therefore be interpreted as the recorded counts with their listed numbers at risk, not as evidence that every enrolled participant was followed or that missing outcomes had no events.

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.

The registry lists serious and other adverse-event counts by group. For the TIV/ Control Group, 3 participants were at risk for serious events and 0 were affected; 3 were at risk for other events and 0 were affected. For the LAIV Group, 8 participants were at risk for serious events and 0 were affected; 8 were at risk for other events and 0 were affected.

These entries describe the counts recorded in the registry. The zero affected counts do not establish that the risk of an event is zero, particularly because the listed groups are small. The registry record does not report confidence intervals, a statistical comparison, details of adverse-event collection, or how relatedness was assessed. No serious adverse-event terms are listed. A death count is not reported in the registry record.

The secondary outcome is the number of participants with related adverse events, while the safety entries separately display serious and other event categories. The record does not provide additional detail on how these categories relate to the secondary outcome definition. The posted counts should therefore be read as descriptive safety information, not as a comparison establishing that one vaccine has a different safety profile.

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

The record establishes that a completed, non-randomized, parallel study enrolled 13 participants and compared groups intended to receive TIV or LAIV. It also identifies the scientific focus as immune responses to seasonal influenza vaccine in nasal and circulating-blood cells. The registered primary outcome, however, is the number of participants in each arm who received vaccine during Day 0 to 28. Its result is not reported in the registry record.

The posted safety entries show 0 affected participants for serious events in each group and 0 affected participants for other events in each group, with 3 at risk in the TIV/ Control Group and 8 at risk in the LAIV Group. These counts describe what the record reports; they do not establish that no adverse events could occur, quantify the underlying risk precisely, or demonstrate equivalent safety between groups. The death figure is not reported in the registry record.

The absence of a reported primary result or analysis means the registry entry cannot establish a difference in vaccine receipt, immune response, or another outcome between groups. It also cannot support a causal conclusion: allocation was non-randomized, masking was absent, and no adjusted comparison is reported. No statistical uncertainty estimates are available for the posted outcome counts.

More generally, a registry result is bounded by the outcomes and methods documented in the record. The study’s stated scientific aim should not be confused with evidence of a measured immune response when quantitative immune-response results are not reported. The information is therefore useful for understanding the registered design and the limited adverse-event counts, but it does not answer whether either vaccine produced a particular immune response or outcome.

14. Why This Trial Matters Statistically

This study illustrates why the registered scientific aim and the reported primary endpoint need to be read separately. The brief summary describes immune responses in nasal and circulating-blood cells, while the primary endpoint is a count of participants who received influenza vaccine during Day 0 to 28. An endpoint that documents intervention receipt does not, by itself, measure the biological response named in the study summary.

The design also highlights the distinction between a vaccine comparator and an untreated control. Although one arm title contains the word “Control,” its description specifies TIV vaccination. The record identifies allocation as non-randomized, so the arms are not a like-for-like randomized control comparison. That limits the causal interpretation of any crude difference, even if outcome values were available.

The safety entries demonstrate another statistical point: zero observed events in small listed groups is a descriptive finding, not proof of zero underlying risk. Precision estimates and fuller reporting of observation and missingness would be needed to characterize uncertainty, but those details are not reported in the registry record.

Finally, a completed status does not ensure that every registered result or analysis is available in the record. Here, the primary endpoint result and statistical analyses are not reported. Distinguishing what was planned, what was measured, and what was actually reported is central to careful interpretation of clinical trial evidence.

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.

Several limitations specific to this record constrain interpretation. The study was non-randomized and unmasked, and the registry does not describe how participants entered each group or whether baseline differences were assessed. The TIV arm is called a control in its title but is described as receiving an active vaccine, so it is not an untreated comparison. These design features make causal interpretation difficult.

The enrollment was 13, while the safety entries list 3 participants at risk in the TIV/ Control Group and 8 in the LAIV Group. The registry record does not explain the relationship between those safety denominators and total enrollment or describe participant flow. It also does not report group sizes in the arm descriptions, loss to follow-up, or the completeness of outcome recording.

The primary outcome result is not reported, and no analyses are listed. Quantitative results for the immune responses identified in the study summary are also not reported in the registry record. The record does not provide a statistical analysis plan, confidence intervals, p-values, an adjustment strategy, or definitions of analysis populations. Methods for handling missing data and assessing adverse-event relatedness are not reported.

The adverse-event entries show zero affected participants in the listed serious and other categories, but the record gives no precision estimates or detail about how events were collected. Deaths are not reported. These limitations mean that the safety counts cannot characterize rare events reliably or establish a comparative safety conclusion. The registry entry also does not report the trial’s own sample-size justification.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Human Mucosal Immune Responses to Influenza Virus (SLVP026) — NCT03023553.
• Registry record last updated 2017-04-21; status last verified 2017-03.
• Results first posted 2017-03-09.
• 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

NCT03023553 is a completed Phase 4, non-randomized, unmasked parallel study sponsored by Stanford University. Its recorded start was 2012-12, primary completion was 2013-02, and enrollment was 13. The listed arms received TIV (Fluzone®) or LAIV (FluMist®), with healthy adult males and females, 18-30 years of age, described in both arm descriptions.

The scientific summary concerns nasal and circulating-blood immune responses. The primary registered outcome is the number of participants in each arm who received influenza vaccine during Day 0 to 28, but its result is not reported in the registry record. The secondary outcome concerns participants with related adverse events. Safety entries list 0 affected participants for serious and other events in both groups; the corresponding numbers at risk are 3 for the TIV/ Control Group and 8 for the LAIV Group. No analyses are listed, and deaths are not reported in the registry record.