Immunogenicity and Safety of Live Attenuated Influenza Vaccine (Flumist) Administered by Nasal and Sublingual Route: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of Live Attenuated Influenza Vaccine (Flumist) Administered by Nasal and Sublingual Route (NCT01488188), a randomized phase 1 study. The primary outcome is Passive Haemagglutination Inhibition Titer..

2. Clinical Question

The study’s stated focus was immunogenicity and safety when live attenuated influenza vaccine was given by nasal or sublingual administration. Its primary outcome was the passive haemagglutination inhibition titer in serum at 21 days after vaccination. The registry reports the median and full range separately for each route. It does not post a statistical comparison between the groups, so the results describe the observed distributions rather than establish whether the routes differ.

The registry identifies three secondary outcome topics: blood IgG and IgA antibody-secreting cell number to flu virus, salivary IgA, and cell-mediated immune responses. Results for those outcomes are not included in the posted primary-result details. Thus the central question that can be answered from the record is limited to the reported serum titer summaries and adverse-event counts. The registry does not report enough information to determine whether the two administration routes produced different immune responses or whether any observed difference would be meaningful beyond this study.

3. Trial Design

The registry describes a randomized, parallel-group phase 1 study with no masking. It lists 40 participants and identifies the study population as healthy. The two groups received influenza vaccine by different routes: sublingual administration and nasal administration. Each group has a posted enrollment count of 20. This is an active-route comparison; the registry does not list a placebo or an unvaccinated group.

The study is marked completed. Its recorded start is 2011-12, and its primary completion is 2013-05. The sponsor is the International Vaccine Institute. The official title describes the study as controlled and focused on the immunogenicity and safety of cold-adaptive live attenuated influenza vaccine in healthy adult volunteers. The registry’s masking entry is none, so the study is recorded as open-label rather than masked.

Random allocation can reduce systematic differences between groups at the point of assignment, but it does not guarantee that groups will be identical, especially in a small study. The registry does not report how the random sequence was generated, whether allocation was concealed, or whether any other procedures were used to support the comparison. It also does not report a detailed protocol, eligibility criteria beyond healthy status, vaccine dose, or the schedule of assessments beyond the primary outcome’s 21-day timeframe. Those details should not be inferred from the study title or background description.

The record lists four outcome measures in total, including the primary outcome and three secondary outcome topics. Although the design is randomized, the posted outcome summaries are descriptive; no statistical analysis comparing the groups appears in the results 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: Randomly group assignment

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.

6. Primary Endpoint

The registry lists the primary outcome as Passive Haemagglutination Inhibition Titer., measured over 21 days after vaccination.

The primary endpoint is the passive haemagglutination inhibition titer measured in serum 21 days after vaccination. A titer is a measure of the extent to which serum can inhibit haemagglutination, an antibody-related laboratory response. In general, such measurements are used to characterize an immune response to an influenza antigen. The endpoint is therefore an immunogenicity measure, not a direct clinical measure of influenza illness or protection.

The registry summarizes the endpoint using the median and full range in each group. A median identifies the middle of an ordered set of observed values. It is less affected by unusually high or low observations than an arithmetic mean, which can be useful when measurements are spread unevenly. The full range gives the lowest and highest observed values, but it does not show how values are distributed between those endpoints. It can also be sensitive to extreme observations.

The posted median is 380.0 for the sublingual group, with a full range of 5.0 to 560.0. For the nasal group, the median is 440.0, with a full range of 10.0 to 1120.0. These are group summaries at the specified timepoint. The registry does not report a confidence interval, a measure of variability around each median beyond the range, or an inferential test of the difference between groups. The summaries alone do not establish the precision of a route-to-route contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median summarize?

The median is the middle value after observations are ordered from lowest to highest. It is a location summary: it describes where the center of the observed values lies, but it does not describe the full shape of the distribution. A median can be useful when observations are skewed or when extreme values might pull an arithmetic mean away from the typical observation. General statistical interpretation still depends on seeing the distribution and knowing how measurements were collected.

For the primary endpoint, the registry gives a median and full range for each administration route. The sublingual group’s median was 380.0 and its range was 5.0 to 560.0. The nasal group’s median was 440.0 and its range was 10.0 to 1120.0. A range records only the smallest and largest observations. It does not reveal how many measurements were close to the median, whether the distribution was skewed, or how stable the median might be under repeated sampling. No confidence interval for the median is posted.

Why is a confidence interval useful?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure. It communicates a range of values compatible with the data and method, rather than presenting a point estimate alone. A confidence interval for a between-group contrast would help readers assess both the direction and precision of the estimated contrast. The registry record does not report such an interval for this outcome. The full ranges of individual observations are not substitutes for confidence intervals: they answer different questions.

What does randomization contribute?

General statistical explanation: random assignment is intended to make treatment-group membership independent of measured and unmeasured participant characteristics at the time of assignment, on average over repeated randomizations. It supports a causal comparison when the study is conducted and analyzed as planned. It does not guarantee balance in every realized study, and it does not by itself address outcomes that are missing, deviations from assigned treatment, or post-randomization exclusions.

The registry describes this study as randomized and parallel, with 20 participants in each route group. It does not report the sequence-generation method or allocation concealment. It also does not say which analysis population was used. The existence of randomization should therefore be noted, while avoiding assumptions about implementation or analysis that are not documented.

Why does the absence of a group comparison matter?

General statistical explanation: a descriptive contrast between two point estimates is not the same as an inferential comparison. An inferential analysis accounts for sampling variability and ordinarily reports an uncertainty measure or test under a specified model. Without a posted comparison, readers cannot determine from the registry whether the observed difference between medians is compatible with substantial sampling variation or represents a precise difference under the analysis assumptions.

No analysis is posted for the primary comparison. The registry record also does not report an adjustment strategy, a model, a test statistic, or a confidence interval. Since the endpoint is reported by median and range, it would be inappropriate to assume that a particular parametric model or test was used. The record does not say whether the investigators analyzed individual measurements, transformed them, adjusted for baseline values, or used any other approach.

What does over-dispersion mean in general?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It matters because a model that understates variability can produce uncertainty estimates that are too narrow and tests that are too liberal. Whether over-dispersion is relevant depends on the outcome type and analysis model. The registry does not report a model or diagnostic assessment for this study, so there is no basis to claim that over-dispersion was assessed or present in these results.

How should planning illustrations be understood?

The study’s own sample-size justification is not reported in the registry record. A separate planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect set as a stated fraction of the observed effect. Such an illustration is not evidence that the trial was designed around that effect, and it is not observed power. Planning calculations depend on assumptions about the effect to detect and the analysis method; changing those assumptions changes the resulting enrollment requirement. Time-to-event planning calculations use total events, while other planning calculations are expressed as participants per arm. No planning count is stated in the registry record being described, so no specific required enrollment can be interpreted from it.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcome topics in addition to the primary serum titer: blood IgG and IgA antibody-secreting cell number to flu virus, salivary IgA, and cell-mediated immune responses. The record indicates four outcome measures overall, but the posted details do not include secondary outcome results. The number of posted analyses is zero. It is therefore not possible to assess how many comparisons were conducted, whether all planned outcomes were analyzed, or whether the investigators adjusted for multiple testing.

Multiplicity is a general statistical concern when many outcomes, timepoints, subgroups, or comparisons are tested. Each additional test can increase the chance of at least one apparently notable result under a setting where no true effects exist. Methods to address multiplicity depend on the analysis plan and the scientific objectives. The registry does not report a multiplicity strategy, and none should be assumed.

The record also does not report missing-data counts or methods for handling missing outcomes. It does not state whether the primary endpoint was available for every randomized participant, whether any participants withdrew, or whether measurements were excluded. The primary outcome population field is blank. It is therefore not reported in the registry record whether the result represents all randomized participants, participants who received vaccination, or another analysis population.

These omissions limit interpretation of both the endpoint summaries and the safety counts. Without missingness information, readers cannot determine whether the posted results include all relevant observations or whether exclusions could affect the group summaries. Without an analysis plan, it is not possible to judge whether reported outcomes reflect prespecified analyses. These are reporting limitations; they do not by themselves establish that data were missing or that analyses were selectively reported.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event entries report zero affected participants among 20 at risk in the sublingual group and zero among 20 at risk in the nasal group. These are the registry’s posted counts. The record does not provide serious adverse-event terms, and it does not describe the events monitored or the period over which safety was assessed. The deaths field is not populated, so a death count is not reported in the registry record; it should not be interpreted as a reported zero.

For other adverse events, the registry reports 3 affected participants among 20 in the sublingual group and 5 among 20 in the nasal group. No event descriptions are included in the posted details. The counts do not show severity, duration, recurrence, or whether events were considered related to vaccination. They also do not provide a formal comparison between the administration routes.

In general, observing no serious adverse events in a small study does not prove that serious events cannot occur. Such counts describe events observed during the recorded study, and their interpretation depends on follow-up, definitions, and completeness of reporting. Those details are not reported in the registry record. The safety information should therefore be read as descriptive counts, not as a definitive assessment of comparative safety.

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

The posted results establish that the registry records two group-level summaries for a laboratory immune-response endpoint at 21 days after vaccination, along with adverse-event counts. The sublingual group’s median titer was 380.0, with a full range of 5.0 to 560.0; the nasal group’s median was 440.0, with a range of 10.0 to 1120.0. The record also reports zero serious adverse events in each group and other adverse events affecting 3 participants in the sublingual group and 5 in the nasal group.

These findings do not establish that one route produces a higher or more reliably measured immune response. The posted results include no confidence interval or statistical test for the route comparison. The observed medians are descriptive values, and the ranges show the spread between the extreme observations rather than uncertainty about the group medians or their contrast. No conclusion about statistical significance can be drawn from the registry entries alone.

The results also do not show whether either route prevents influenza illness. The primary endpoint is a serum antibody-related titer, not a clinical outcome such as influenza infection or symptoms. Although the study background discusses live attenuated influenza vaccines, background context is not a result of this trial. The registry does not post clinical efficacy findings for this study.

The record does not establish equivalence or non-inferiority between routes. Such conclusions require a prespecified framework, an appropriate margin where relevant, and an analysis with uncertainty estimates. None is reported in the posted results. Likewise, the adverse-event counts do not establish that the routes have identical safety profiles, particularly because event descriptions, follow-up details, and comparative analyses are not reported.

The appropriate interpretation is consequently narrow: the registry records the observed primary outcome summaries and adverse-event counts for a small randomized phase 1 study in healthy volunteers. The information can describe what was observed in these groups, but it cannot resolve the comparative question with quantified precision or support conclusions about clinical protection.

13. Why This Trial Matters Statistically

This trial illustrates a common distinction in clinical biostatistics: having randomized groups and numerical outcome summaries does not necessarily mean that a comparative estimate is available. The registry identifies two randomized routes, provides a median and full range for each, and records adverse-event counts. Yet it posts no analyses for the groups. Readers can describe the observations, but cannot use the record to quantify uncertainty in the route contrast.

The choice of summary also matters. A median and full range provide a compact view of a distribution, but they answer different questions. The median locates the center, while the range identifies the observed extremes. Neither by itself reveals the uncertainty of the median or the precision of a between-group comparison. This is particularly important when the distributions span different ranges and no formal comparison is reported.

The record also demonstrates why outcome reporting and analysis reporting are distinct. It names a primary immunogenicity outcome and three secondary outcome topics, but secondary results are not included in the posted details. Without results and an analysis plan, readers cannot evaluate the full set of intended comparisons or determine how multiplicity was handled.

Finally, early-phase studies have a different interpretive role from trials designed to establish clinical efficacy. This study’s registry record focuses on immunogenicity and safety in healthy volunteers. Its laboratory endpoint can characterize an immune response, but does not directly answer whether vaccination prevents illness. Clear separation of descriptive immune measurements, comparative statistical evidence, and clinical outcomes is essential to avoid reading more into the results than the record supports.

14. 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 registry record leaves several trial-specific details unreported. It does not state the vaccine dose, the full eligibility criteria, the method used to generate the random sequence, or whether allocation was concealed. It records no masking. These gaps constrain assessment of the conduct of the comparison and the applicability of the findings beyond the listed healthy volunteer population.

The primary result is reported only as a median and full range for each group. No confidence interval, formal between-group test, adjusted estimate, or analysis model is posted. The registry also reports no analyses overall. Consequently, the uncertainty around the observed summaries and any route contrast cannot be evaluated from the posted results.

The registry does not report baseline immune measurements, changes from baseline, individual observations, or the distribution of titers beyond the median and range. It does not state whether each randomized participant contributed a measurement at 21 days. The analysis population is not specified, and missing-data handling is not reported. These omissions make it difficult to assess completeness and to understand precisely which participants contributed to the endpoint summaries.

Safety reporting is similarly limited: serious-event counts are given, but terms and follow-up details are not reported. Other adverse-event counts are listed without event descriptions. The deaths field is not populated, so a death count is not reported in the registry record. There is no posted comparison of safety outcomes.

Finally, no sample-size justification, statistical analysis plan, or multiplicity approach is reported in the registry record. The study’s phase 1 designation and enrollment of 40 describe its registered context, but do not substitute for those missing design and analysis details. These limitations call for a descriptive reading rather than a definitive comparative conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of Live Attenuated Influenza Vaccine (Flumist) Administered by Nasal and Sublingual Route — NCT01488188.
• Registry record last updated 2013-12-23; status last verified 2013-11.
• Results first posted 2013-12-23.
• 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.

18. Record Summary

NCT01488188 is a completed phase 1 randomized, unmasked, parallel study sponsored by the International Vaccine Institute. The registry lists 40 healthy adult volunteers, with 20 assigned to sublingual influenza vaccine administration and 20 to nasal administration. The recorded study start is 2011-12, and primary completion is recorded as 2013-05.

The primary outcome was serum passive haemagglutination inhibition titer 21 days after vaccination, summarized by median and full range. The sublingual group’s median was 380.0, with a range of 5.0 to 560.0; the nasal group’s median was 440.0, with a range of 10.0 to 1120.0. The registry reports zero serious adverse events in both groups, and other adverse events affecting 3 participants in the sublingual group and 5 in the nasal group.

Three secondary outcome topics are listed, but no analyses are posted. A formal comparison, confidence intervals, missing-data methods, and analysis populations are not reported in the registry record. The results are therefore descriptive and do not establish comparative immunogenicity, comparative safety, or clinical protection.