LT Vaccine Patch Self-Administration Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LT Vaccine Patch Self-Administration Study (NCT00565461), a randomized phase 2 study. The primary outcome is GMTs After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch..

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group Phase 2 study. The registry record lists 160 participants as the enrollment. It describes four groups, each with 40 subjects, and compares patch administration by a clinician with self-administration in the clinic or away from the clinic. Because the study was open-label, participants and clinicians were not masked to who applied the patch. The record does not report further details about sequence generation, allocation concealment, or how randomization was implemented.

All four groups began with a clinician-administered LT patch on the left deltoid. The groups differed in the second administration. One group received the second patch from a clinician on the right deltoid. Another received the second patch from a clinician on the left thigh. A third received the second patch by self-application in the clinic on the left thigh. The fourth self-applied the second patch at home on the left thigh. The arm descriptions state that the second treatment followed the first by two weeks or fourteen days, depending on the description. The patch contained 37.5ug LT.

The trial start is recorded as 2007-11, and primary completion is recorded as 2008-07. The status is completed. The registry record lists Day 0, Day 14, Day 21, Day 28, Day 35, and Day 194 as the primary outcome timeframe. It does not report actual participant flow, adherence to self-administration, or the number of participants contributing data at each measurement time. These omissions limit assessment of how closely the analyzed groups followed the intended regimens.

The planned comparisons address more than administration setting: the clinician-administered groups also differ in second-dose site. Secondary outcomes include comparisons of immunogenicity and safety by site and setting, including GMT, GMFR, and SCR measures. Results for these comparisons 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: intent to treat population = primary analysis population; defined as all study subjects who were consented, randomized, and had a baseline serology

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 GMTs After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch., measured over Day 0, Day 14, Day 21, Day 28, Day 35, Day 194.

The primary outcome is titled as GMTs after a self-administered LT vaccine patch, in the clinic or away from the clinic, compared with a clinician-administered patch. GMT means geometric mean titer: a summary of antibody measurements calculated on a logarithmic scale and expressed back on the original scale. This approach is commonly used for antibody titers because values can be strongly skewed and can vary multiplicatively. In general, the GMT describes a group’s central antibody level; it does not show how responses are distributed among individual participants.

The endpoint description also specifies GMFRs and seroconversion rates for LT IgG and IgA. GMFR summarizes the geometric mean change in antibody response between measurements, while SCR is the proportion meeting a defined seroconversion criterion. The specific seroconversion definition is not reported in the registry record. The endpoint unit is geometric mean titers, and the listed dispersion measure is a 95% confidence interval.

The planned timeframe includes Day 0, Day 14, Day 21, Day 28, Day 35, and Day 194. Repeated measurements can describe the trajectory of antibody responses rather than a single snapshot. However, the registry record does not provide numerical GMTs, GMFRs, SCRs, confidence limits, or inferential comparisons at those time points. It therefore permits description of what was intended to be measured, but not an estimate of the magnitude or precision of the observed immune responses.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying the contrast being estimated. This study has four groups, with differences in who administered the second patch, where it was administered, or both. The primary outcome title emphasizes self-administration in the clinic or away from the clinic compared with clinician administration. The endpoint description specifies the deltoid/thigh regimen. Because the registry record does not report the numerical analyses, the precise contrast estimates and their uncertainty cannot be assessed.

What does a geometric mean titer represent?

In general, a geometric mean is calculated by transforming positive measurements to a logarithmic scale, averaging them there, and transforming the average back to the measurement scale. For antibody titers, this can be a useful summary when values vary multiplicatively or have a skewed distribution. It describes a group-level central value; it does not mean that every participant had a response near that value. Individual variation and the distribution of responses require additional summaries.

The primary endpoint lists a 95% confidence interval for GMTs. In general, a confidence interval expresses the uncertainty associated with an estimated quantity under the assumptions of the statistical method. A narrower interval indicates greater precision than a wider interval, but an interval alone does not establish clinical importance. The registry record provides no interval limits, so the precision of the planned GMT estimates cannot be judged.

How do GMFR and seroconversion complement GMT?

In general, a GMFR describes change in antibody response between measurements using a geometric summary. It addresses response relative to a participant’s earlier measurement, while GMT describes the group’s antibody level at a measurement time. SCR summarizes the fraction of participants who meet a specified seroconversion rule. These measures answer related but different questions: a group can have a particular central antibody level, a particular average fold rise, and a particular proportion meeting a response criterion. The registry record does not report the seroconversion rule or the observed values for these outcomes.

The primary timeframe includes Day 0, Day 14, Day 21, Day 28, Day 35, and Day 194. Repeated measurements can be analyzed in several ways, such as separate summaries at each time or a model that accounts for measurements from the same participant being related. In general, repeated observations from one person are not independent. The registry record does not report which approach was used, how within-person correlation was handled, or whether adjusted estimates were produced.

What does randomization contribute?

In general, random assignment can reduce systematic differences between groups at the outset, supporting a causal comparison when the trial is conducted and analyzed appropriately. It does not ensure that groups are identical in every characteristic, especially in a study of this size, nor does it resolve problems caused by missing outcome data or differences in adherence. Here, the record identifies randomized allocation but does not report the randomization procedure, baseline characteristics, participant flow, or adherence results. Those details are needed to evaluate how well the intended comparison was maintained.

The study was open-label, meaning that masking was absent. In general, awareness of assigned administration method can influence behavior, reporting, or assessment, depending on the outcome and study procedures. Laboratory antibody measurements may be less susceptible to subjective assessment than reported symptoms, but the record does not describe laboratory masking or assay procedures. It would therefore be inappropriate to assume that outcome assessment was blinded.

What can the planning illustration establish?

The registry includes planning assumptions for illustrative sample-size calculations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration considers an effect that is a stated fraction of the observed effect. Such planning calculations are not the trial’s original design justification, and they are not observed power. The registry record does not report the trial’s own sample-size justification or the numerical planning results. Sample-size illustrations do not replace reporting estimates, confidence intervals, and analysis methods for the trial outcomes.

The primary endpoint has several measures and time points, and the registry record does not report a complete statistical analysis plan. It does not state which outcome comparisons were designated for formal hypothesis testing, how multiple comparisons were handled, or whether any interim analyses occurred. In general, multiple testing can increase the chance of finding an apparently noteworthy result by chance when many outcomes or time points are examined. Methods such as prespecifying a primary contrast or adjusting inference can address that issue, but the registry record does not say which methods were used.

No numerical primary results are posted. There is therefore no basis in the registry record for recalculating a comparison from summary statistics, assessing agreement with a sponsor analysis, or judging whether estimates are consistent with a null difference. Statistical methods can explain how the intended outcomes would ordinarily be interpreted, but they cannot supply absent trial estimates.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome spans several antibody measures and assessment times. The endpoint description names GMTs, GMFRs, and seroconversion rates for LT IgG and IgA, while the listed timeframe includes Day 0, Day 14, Day 21, Day 28, Day 35, and Day 194. Secondary outcomes add comparisons by vaccination site and by self-administration setting. In general, evaluating many outcomes or time points can raise multiplicity concerns: the more comparisons considered, the greater the chance that some may appear notable by chance alone. A prespecified primary contrast and a clear multiplicity strategy help readers distinguish confirmatory analyses from exploratory ones. The multiplicity approach is not reported in the registry record.

The record does not report whether interim analyses were conducted or provide a statistical analysis plan. It also does not report numerical endpoint results, estimates, confidence intervals, or p-values. No claim about statistical significance or multiplicity-adjusted findings can therefore be made from the registry information.

The stated intent-to-treat population includes consented and randomized subjects with baseline serology. The record does not provide analysis counts at each assessment, reasons for missing measurements, or the method used to address missing data. In general, missing-data methods matter because the validity of an estimate can depend on why data are absent and whether the assumptions behind the method are plausible. The registry record does not state whether analyses used complete cases, imputation, or another approach. It also does not report a separate per-protocol analysis population or sensitivity analyses.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (2.5%), brugada syndrome (2.5%), colitis (2.5%), intervertebral disc protrusion (2.5%), menorrhagia (2.5%).

The registry’s serious-adverse-event summary reports 1 affected participant among 40 at risk in the clinician-administered deltoid group, 3 among 40 in the clinician-administered thigh group, and 0 among 40 in each self-administered group. These are descriptive counts in the registry record, not adjusted comparisons or evidence that one administration approach is safer than another. The record does not report event timing, duration, seriousness criteria, relatedness to vaccination, or the details needed to interpret the group differences.

The registry also lists the serious-event terms Acute myocardial infarction, Brugada syndrome, Colitis, Intervertebral disc protrusion, and Menorrhagia, each with a reported value of 2.5%. The record does not make clear in this summary how those terms relate to the group-level counts, so they should not be assigned to a particular group based on the listing alone. Death counts are not reported in the registry record.

For other adverse events, the record lists 40 affected participants among 40 at risk in each group. This summary does not specify event types, severity, or whether the figures represent participants with at least one event or another reporting convention. The listed counts should therefore be read as registry summaries, not as a complete account of tolerability or a basis for a comparative safety conclusion.

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

The registry record establishes that this was a randomized, open-label Phase 2 trial comparing different ways of administering an LT vaccine patch. Its primary question concerned immune responses after a self-administered second vaccination compared with clinician administration, with attention to whether self-administration occurred in the clinic or away from the clinic. The design also included clinician-administered regimens that varied by the site of the second patch. The stated outcomes include GMT, GMFR, and SCR measures for LT IgG and IgA.

What the registry record does not establish is the size or direction of any immune-response difference. It contains no numerical primary endpoint results, confidence intervals, or inferential statistics. It therefore cannot show whether the groups’ antibody responses were similar, different, or estimated with adequate precision. The fact that outcomes were planned and a trial was completed is not itself evidence of a particular result.

The safety information is also limited to summary adverse-event counts and terms. It does not provide enough detail to determine causality, compare risks reliably, or understand the clinical context of the listed events. A count of zero in a group does not demonstrate absence of risk, and a difference in counts alone does not establish that the assigned administration method caused the difference.

In general, trial findings apply most directly to the population, procedures, and measurements actually studied. Here, the registry record identifies a population definition and describes four administration regimens, but it does not provide participant characteristics, adherence, outcome data completeness, assay methods, or sufficient analysis details. Those gaps prevent a full evaluation of generalizability and potential sources of bias. The results cannot be used to make an individual treatment decision; they describe a study question and incomplete registry reporting rather than a complete evidence assessment.

13. Why This Trial Matters Statistically

Statistically, this trial is notable because its question separates the act of self-administration from the setting in which that act occurs. It includes self-application in the clinic and self-application at home, alongside clinician-administered regimens. That structure can help frame questions about whether administration setting and administrator matter, but comparisons need to be interpreted in light of the other differences between groups. In particular, the clinician-administered groups used different sites for the second patch, so not every contrast isolates administration method alone.

The endpoint plan also illustrates why a single label such as immunogenicity can conceal several statistical questions. GMT describes a group-level antibody level, GMFR describes change, and SCR describes the proportion meeting a response criterion. Assessments across Day 0, Day 14, Day 21, Day 28, Day 35, and Day 194 address response over time. Each measure and assessment can contribute useful information, but the multiplicity strategy and the way repeated measurements are modeled affect interpretation. Those analysis details are not reported in the registry record.

The record also makes clear why design information and results reporting must be considered separately. Randomization, group descriptions, and a stated primary population describe how the study was intended to generate evidence. They do not substitute for endpoint estimates, uncertainty intervals, participant flow, and missing-data methods. Without those results, neither the statistical strength nor the practical meaning of the planned comparisons can be assessed. The registry record is useful for identifying the intended questions, but it does not supply the outcome evidence needed to answer them.

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 main trial-specific limitation is that the registry record does not report numerical primary immunogenicity results. No GMT estimates, GMFR values, SCR results, confidence intervals, or p-values are available in the record. This prevents assessment of effect size and precision, and means the planned primary question cannot be answered from the posted registry information.

The four groups differ along more than one dimension. The self-administered groups received the second patch on the left thigh, while clinician administration included both deltoid and thigh regimens. As a result, comparisons involving different groups may combine administration-method and site differences. The record does not provide analysis results that would show which contrasts were estimated or how those design features were handled.

Although the primary analysis population is defined, participant flow and analysis counts by time point are not reported. The registry record also does not state how missing measurements were handled, whether all randomized participants were analyzed as intended, or whether sensitivity analyses were conducted. Adherence and the success of home self-administration are not reported. These details are especially relevant for interpreting a trial that compares administration settings.

The study was open-label, and the record does not report whether laboratory staff assessing antibody outcomes were masked or describe assay methods. The statistical analysis plan, multiplicity handling, randomization procedure, sample-size justification, and interim analyses are not reported in the registry record. The safety summaries lack event-level context, including timing and relatedness. Together, these limitations constrain interpretation beyond the trial’s stated aims and design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: LT Vaccine Patch Self-Administration Study — NCT00565461.
• Registry record last updated 2020-03-30; status last verified 2020-03.
• Results first posted 2014-04-21.
• 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.

18. Record Summary

NCT00565461 is a completed randomized, open-label, parallel-group Phase 2 study of an LT vaccine patch for prevention of travelers' diarrhea. The registry lists enrollment of 160 and describes four groups, each with 40 subjects. Participants received a clinician-administered first patch, followed by a clinician-administered or self-administered second patch; self-administration occurred in the clinic or at home. The primary question concerned immunogenicity, with GMTs emphasized in the primary outcome title and GMFR and SCR measures also described. The primary timeframe lists Day 0, Day 14, Day 21, Day 28, Day 35, and Day 194. The registry record reports limited adverse-event summaries but does not report numerical primary endpoint results or key details of the statistical analysis and missing-data handling. The trial’s intended comparisons can be described, but their outcome estimates and precision cannot be assessed from the registry record.