T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 2, 2010: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 2, 2010 (NCT03022396), a non-randomized phase 4 study. The primary outcome is Number of Individual Twins Who Received Influenza Vaccine.

2. Clinical Question

3. Trial Design

This was a Phase 4, non-randomized, parallel study sponsored by Stanford University. The record gives enrollment as 82 and status as completed. The recorded study start is 2010-09, and primary completion is 2011-01. Its stated purpose was to investigate responses to influenza vaccines in monozygotic and dizygotic twins of different ages. The registry lists Influenza as the condition.

The descriptions identify six groups distinguished by age and whether twins were identical or fraternal. Groups A through E were described as receiving Fluzone® intramuscularly. Group F, consisting of identical twins aged 70 - 100, could receive Fluzone® or High Dose Fluzone® intramuscularly. The record does not report how participants were allocated to the groups or, within Group F, how the vaccine options were chosen.

The design is non-randomized and unmasked. As a general statistical matter, non-random allocation means that observed differences between groups can reflect differences in participant characteristics or selection as well as any treatment difference. Here the groups also differ by age range and twin type, so direct comparisons do not isolate a vaccine effect. The registry itself cautions that the arms are not a like-for-like control comparison.

A parallel design means participants are described within groups rather than in a reported crossover sequence. The registry record does not report a protocol-level account of visit schedules beyond the primary outcome timeframe, allocation procedures, masking procedures beyond NONE, or the rationale for the group structure. It also does not report a sample-size justification or statistical analysis plan. The enrollment figure should not be read as the number with a reported primary outcome: the outcome counts by group 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

Analysis population for the primary outcome, as defined in the registry: All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.

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: All numbers reflect the number of individual participants, not the number of twin pairs. Ie, in Group A there were 16 participants who were part of 8 twin pairs.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Individual Twins Who Received Influenza Vaccine, measured over Day 0 to 28.

The primary outcome is titled Number of Individual Twins Who Received Influenza Vaccine. Its unit is participants, and its timeframe is Day 0 to 28. The description explicitly clarifies that each twin member was counted individually rather than counting twin pairs. This distinction matters because the unit of analysis in the reported endpoint is the individual participant, not the family pair.

As a general statistical concept, a count endpoint describes how many people meet a stated event definition. It can summarize whether vaccine was received during a specified period, but it does not by itself measure immune response, protection from infection, or a biological response to vaccination. Those questions require outcome definitions and results distinct from the count of vaccine recipients.

The registry record does not report the primary outcome count for any group, nor does it provide a group-specific denominator for this endpoint. The enrollment figure is not a substitute for those results. Without the counts and denominators linked to the endpoint, it is not possible to describe the observed receipt pattern or make a numerical comparison across groups. The endpoint definition is available, but its result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

As a general statistical concept, a participant count records the number of people meeting an outcome definition. It is not interchangeable with a proportion, a rate, or an effect estimate. To interpret a count across groups, the reader usually needs the number counted and the relevant denominator, along with a clear definition of what qualifies as an event. Here the endpoint definition specifies vaccine receipt and says that twins are counted individually. The registry record does not report the group-specific primary outcome counts or denominators, so no primary-endpoint rate or between-group effect can be described.

The enrollment figure is a study-level registration value, not a substitute for observed endpoint data. Enrollment alone does not show whether participants completed follow-up, received vaccine, or contributed to a particular analysis. The record does not report those details for the primary outcome.

Why does non-random allocation matter?

As a general statistical concept, random allocation helps balance prognostic characteristics across treatment groups on average. In a non-randomized study, groups can differ for reasons related to how participants entered or were assigned to them. Any observed outcome contrast can therefore combine a treatment contrast with differences in participant characteristics, clinical context, or selection. Adjustment can sometimes address measured differences, but it cannot be assumed to remove all confounding, and no adjusted analysis is reported in the registry record.

This study's groups are defined by age ranges and twin type, and the record identifies it as non-randomized. It also states that the arms are not a like-for-like control comparison. Accordingly, a crude comparison among groups would not establish a causal vaccine effect. The posted information does not report a prespecified comparative estimand or an analysis that accounts for these group differences.

What does the twin structure imply?

As a general statistical matter, outcomes from members of a twin pair may be correlated because they share familial and environmental features. Treating correlated observations as if they were fully independent can make uncertainty estimates too small. Appropriate methods may account for clustering or paired structure, depending on the research question and data collection. The primary outcome description clarifies that each twin is counted as an individual participant, but it does not explain how dependence within pairs was handled in analyses. No primary-outcome analysis is reported, so the registry record does not show whether any correlation adjustment was used.

What can confidence intervals and p-values tell readers?

As a general statistical concept, a confidence interval expresses uncertainty around an estimated quantity under specified assumptions and a statistical method. A narrow interval indicates greater precision than a wide interval, while neither width nor interval placement alone establishes that an estimate is clinically meaningful. A p-value describes how compatible data are with a stated statistical model and null hypothesis; it does not measure the size or importance of an effect.

The registry record does not report an estimate, confidence interval, or p-value for the primary endpoint. It lists zero analyses. Therefore, there is no reported inferential result to interpret, and no precision assessment can be made from the primary outcome. These omissions should not be filled by treating the enrollment value as an analysis result.

How should the adverse-event counts be understood?

As a general statistical concept, observed event counts depend on the event definition, the population monitored, and the period of observation. A zero count means no event was recorded in the reported group data; it does not prove that the underlying event risk is zero. When events are uncommon, the amount of information about risk can remain limited even when none are observed. A comparison of safety between groups would also require suitable denominators, comparable observation, and a prespecified analysis. The registry record gives group-specific at-risk counts and zero affected counts, but does not report a comparative safety analysis or sufficient detail to infer a general risk level.

The record's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such planning illustrations are not observed power and are not evidence that the study was designed with a particular justification. The registry record does not report the trial's own sample-size justification, and no comparative effect is reported from which to interpret a planning calculation as a trial result.

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("Group A: Age 8-17 yo Identical Twins", "Group B: Age 18-30 yo Identical Twins", "Group C: Age 18-30 yo Fraternal Twins", "Group D: Age 40 - 59 yo Identical Twins", "Group E: Age 40 - 59 yo Fraternal Twins", "Group F: Age 70 - 100 yo Twins")
n      <- c(16, 14, 10, 20, 14, 8)
events <- c(16, 14, 10, 20, 14, 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  Group A: Age 8-17 yo Identical Twins  16  16  100.0  79.4  100.0  80.6  100.0  80.5  99.9
ARM  Group B: Age 18-30 yo Identical Twins  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8
ARM  Group C: Age 18-30 yo Fraternal Twins  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8
ARM  Group D: Age 40 - 59 yo Identical Twins  20  20  100.0  83.2  100.0  83.9  100.0  83.9  99.9
ARM  Group E: Age 40 - 59 yo Fraternal Twins  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8
ARM  Group F: Age 70 - 100 yo Twins  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and identifies vaccine receipt as the primary outcome, with a secondary outcome concerning the number of individual twins with related adverse events. It lists no analyses. It does not report a multiplicity strategy, such as a hierarchy among outcomes, an adjustment for multiple testing, or a distinction between confirmatory and exploratory analyses. The absence of a reported strategy means readers cannot determine how the study handled the possibility of false-positive findings across multiple outcomes or comparisons.

Missing-data handling is not reported in the registry record. The record does not state how incomplete follow-up, missing outcome assessments, or participants without recorded vaccine receipt were handled. It also does not report an analysis population definition, such as whether results were intended for all enrolled participants or for a subset with observed endpoint data. Enrollment alone cannot resolve these questions.

Because no analyses are listed and the primary outcome counts are not reported, there is no basis for assessing exclusions, imputation, sensitivity analyses, or the impact of missing observations. These omissions limit interpretation of both the endpoint and the reliability of any potential group comparison. They do not establish that data were missing or that a particular analysis method was used; those details are simply not reported in the registry record.

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.

The registry reports serious adverse-event counts and other adverse-event counts by study group. For Groups A through F, the serious-event count is zero and the other-event count is zero. Deaths are also recorded as zero in each group. The listed at-risk counts are 16 for Group A, 14 for Group B, 10 for Group C, 20 for Group D, 14 for Group E, and 8 for Group F. These are counts of individual participants in the group safety data, not twin pairs.

As a general statistical principle, zero recorded events means that none were reported in the registry's group counts; it does not establish that the true risk is zero. These counts do not by themselves quantify comparative risk, and the non-randomized group structure limits direct safety comparisons. The registry record does not report a statistical comparison of adverse events, detailed event descriptions, or further information about observation and ascertainment. The listed secondary outcome refers to twins with related adverse events, but the posted counts alone should not be extended to outcomes or follow-up details that are not reported.

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

The study record establishes that a completed, non-randomized, parallel investigation of seasonal influenza vaccine responses in twins was registered. It identifies groups by age and twin type, lists Fluzone® as the vaccine for Groups A through E, and lists Fluzone® or High Dose Fluzone® for Group F. It also defines the primary outcome as the number of individual twins who received vaccine during Day 0 to 28. Those details describe the study's structure and intended measurement.

The record does not report the primary outcome counts, group-specific receipt results, or any inferential analyses. It therefore cannot show the observed level of vaccine receipt by group, estimate a difference between vaccine formulations, or establish an association between age or twin type and receipt. The record also does not report immune-response results in the information, despite the study's stated interest in immune response. A study objective is not itself a result.

The zero adverse-event counts and zero deaths are descriptive observations in the registry record. They do not demonstrate absence of risk, and they do not establish comparative safety. Similarly, the enrollment value is not evidence of complete follow-up or an analysis sample for the primary endpoint.

The non-randomized design and non-equivalent group descriptions further constrain causal interpretation. Even if group results were available, differences could reflect group composition or assignment processes rather than vaccine effects. No adjusted or other comparative analysis is reported. The appropriate reading is therefore limited: the registry documents the design, intervention options, endpoint definition, and reported safety counts, while leaving the primary outcome results and comparative conclusions unreported.

14. Why This Trial Matters Statistically

This trial illustrates why a registered outcome definition and an outcome result are not the same thing. The primary endpoint is clearly described as a count of individual twins who received influenza vaccine during Day 0 to 28. However, the registry record does not report the group counts for that endpoint. Without counts and denominators, the endpoint cannot be converted into a meaningful group-level comparison, and there is no reported estimate whose precision can be evaluated.

The design also makes the interpretation of comparisons important. Participants were placed in non-randomized groups defined by age and twin type, while Group F could receive either of two vaccine formulations. As a general principle, such group differences can complicate causal interpretation because treatment and participant characteristics may not be separable. The registry itself cautions that the arms are not like-for-like controls. That caution is central to statistical reading, not merely a technical detail.

The twin setting raises a further general issue: observations within a twin pair may be correlated. The endpoint counts twins individually, but the record does not describe how pair-level dependence would be handled in analysis. This highlights the distinction between the unit counted and the structure that may matter for valid uncertainty estimates.

Finally, the adverse-event counts demonstrate the limits of interpreting zero observed events. Counts can be reported transparently while still leaving uncertainty about risk and comparison. Together, these features make the registry useful for understanding study structure and reporting gaps, but insufficient for drawing quantitative conclusions about vaccine receipt, immune response, or comparative effects.

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 primary outcome results are not reported in the registry record. In particular, there are no group-specific counts of participants who received vaccine, and no endpoint denominators are reported. The enrollment value cannot substitute for those details. Consequently, the primary endpoint cannot be compared across groups or assessed for precision.

The study is non-randomized, and the registry explicitly warns that the arms are not a like-for-like control comparison. Group descriptions vary by age and twin type; Group F additionally includes two vaccine options. The record does not report the allocation process, how the Group F vaccine choice was made, or an analysis intended to address differences between groups. Causal conclusions are therefore unsupported by the posted information.

The record does not report immune-response results, although the study's stated purpose concerns immune responses. It lists no analyses and does not describe statistical methods for handling twin-pair correlation, missing data, multiplicity, or analysis populations. The registry record also does not report a sample-size justification, interim analyses, or a statistical analysis plan. These details should not be inferred from the design label or enrollment value.

Safety information is limited to the reported group counts. The record does not provide a comparative safety analysis or further details needed to interpret event ascertainment and follow-up. These limitations restrict interpretation to the registered design and the outcomes actually reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 2, 2010 — NCT03022396.
• Registry record last updated 2017-08-21; status last verified 2017-08.
• Results first posted 2017-08-21.
• 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

NCT03022396 is a completed, Phase 4, non-randomized, unmasked, parallel study sponsored by Stanford University. The record gives enrollment as 82, with a recorded start of 2010-09 and primary completion of 2011-01. It concerns seasonal influenza vaccination and responses in monozygotic and dizygotic twins across age-defined groups.

Fluzone® was listed for Groups A through E; Group F could receive Fluzone® or High Dose Fluzone®. The primary outcome was the number of individual twins who received vaccine during Day 0 to 28. The registry record does not report the primary outcome counts or analyses. It reports zero serious affected participants, zero other affected participants, and zero deaths in each group. The listed arms are not described as like-for-like controls, limiting direct comparisons.