This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Traveler's Diarrhea (TD) Automated Process (NCT00751777), a randomized phase 2 study. The primary outcome is Geometric Mean Titer (GMT) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00751777 |
| Phase | Phase 2 |
| Condition | Prevention of Travelers' Diarrhea |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 120 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Intercell USA, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults enrolled in a study of prevention of travelers’ diarrhea. The primary outcome population was the Immunogenicity Evaluable Population: subjects who were consented and randomized, received both assigned vaccinations, and had immunogenicity blood tests at baseline (Day 0) and at Day 21 and Day 35.
Intervention
A two-vaccination regimen delivered by a patch containing heat-labile enterotoxin of E. coli (LT). The arm description specifies a 37.5 µg LT patch.
Comparator
A two-vaccination regimen using a placebo patch. The study was randomized, double-blind, placebo-controlled, and quadruple-masked according to the registry record.
Primary question
How did geometric mean titers (GMTs) after the first and second LT patch vaccinations compare with placebo, across the specified assessment days? The registry record identifies GMT and its 95% confidence interval as the primary outcome measure, but the results are not reported in the registry record.
The study was designed to evaluate and compare immune responses and safety following the patch regimen. Its stated focus is immunogenicity and safety, not a clinical outcome such as the occurrence of travelers’ diarrhea. Therefore, the primary question concerns measured immune responses over the listed follow-up schedule, rather than whether participants experienced a particular degree of protection from illness.
3. Trial Design
This was a randomized, double-blind, placebo-controlled Phase 2 study with a parallel-group model and quadruple masking. It compared a two-vaccination regimen using an LT patch with a two-vaccination regimen using a placebo patch in healthy adults. The registry lists planned enrollment as 120 and describes 80 subjects in the 37.5 µg LT patch group and 40 subjects in the placebo group. These are the planned arm descriptions; the safety counts recorded elsewhere in the registry do not exactly match those planned arm sizes.
The study’s stated purpose was to compare immune responses and safety after transcutaneous immunization with LT patches or placebo patches. The primary outcome was GMT after the first and second vaccinations, with assessments scheduled for Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, and Day 194. The primary analysis population was defined more narrowly than everyone enrolled: it required both vaccinations and blood testing at baseline, Day 21, and Day 35.
The registry gives a start date of 2008-09 and a primary completion date of 2009-11, and lists the study status as completed. It also lists secondary outcomes concerning safety after the first and second vaccinations, residual LT in the patch and at the skin site after wear, and LT-specific immune responses at one year in the LT patch group. Several entries repeat the one-year immune-response outcome wording. The registry lists 8 outcome measures and 0 analyses. Detailed methods for random sequence generation, allocation concealment, treatment adherence, protocol deviations, and statistical analysis 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
| Stage | Group 1: 37.5 µg LT Patch | Group 2: 0 µg LT Patch (Placebo) |
|---|---|---|
| STARTED | 81 | 39 |
| COMPLETED | 70 | 36 |
| NOT COMPLETED | 11 | 3 |
Analysis population for the primary outcome, as defined in the registry: Immunogenicity Evaluable Population (IEP): all study subjects who are consented, randomized, received the assigned treatments (both vaccinations), and had blood drawn for immunogenicity testing at baseline (Day 0) and both of the following time points: Day 21 and Day 35.
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: Intent-to-Treat (ITT) Population: all study subjects who were consented, randomized, and had a baseline serology
| Characteristic | Unit | Group 1: 37.5 µg LT Patch | Group 2: 0 µg LT Patch (Placebo) | Total |
|---|---|---|---|---|
| Participants analysed | 81 | 39 | 120 | |
| Age, Continuous | years | 34.1 (SD 10.2) | 35.3 (SD 13.0) | 34.5 (SD 11.2) |
| Sex: Female, Male: Female | Participants | 46 | 26 | 72 |
| Sex: Female, Male: Male | Participants | 35 | 13 | 48 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean Titer (GMT) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo, measured over Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, Day 194.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | geometric mean titer |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is geometric mean titer (GMT), an immunogenicity measure reported at the scheduled assessment days. The registry specifies a 95% confidence interval as the dispersion measure. GMT summarizes antibody titer measurements on a geometric scale, which is often used for immune-response data because titers can vary over a wide range and may be more appropriately summarized after logarithmic transformation. That is a general statistical rationale; the registry record does not describe the transformation or computational procedure used for this study.
The scheduled assessments span baseline and follow-up after vaccination: Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, and Day 194. The stated primary outcome title refers to GMT after the first and second vaccinations and comparison against placebo. This repeated schedule can describe how measured immune responses change over time and how the groups compare at the planned assessment points. The registry does not reduce these multiple time points to one comparison.
The specified Immunogenicity Evaluable Population requires blood draws at Day 0, Day 21, and Day 35, as well as receipt of both assigned vaccinations. This definition makes the endpoint conditional on having the specified treatment and assessment history. The registry does not report the GMT values, confidence intervals, or group comparisons, so the magnitude and precision of the observed immune responses cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study intended to compare immune responses and safety between an LT patch regimen and placebo. It identifies GMT as the primary measure and lists assessment days from Day 0 through Day 194. However, no numerical primary endpoint results or group comparisons are reported in the registry record. Consequently, the size, direction, and precision of any observed difference in GMT cannot be described from this information.
The 95% confidence interval is named as the dispersion measure for GMT, but no interval limits are recorded. In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. Its width can help readers judge precision, while its location indicates the range of estimates compatible with the data and method. Without reported estimates and interval limits, neither feature can be evaluated for this trial.
The primary outcome spans several assessment days and refers to responses after both vaccinations. The registry’s note that the primary outcome has several categories or time points and was not reduced to one comparison is important: there is no single posted result to treat as the definitive comparison. Results at different assessment days could address different aspects of the response profile, and they should not be collapsed into a claim about an overall effect unless the analysis defines and supports such a summary. The analysis plan and any multiplicity adjustment are not reported in the registry record.
The primary endpoint population is the Immunogenicity Evaluable Population, which requires both vaccinations and blood draws at baseline, Day 21, and Day 35. It is therefore not simply described as everyone randomized. The registry does not report how many participants met this definition, how missing blood tests were handled, or whether another population was used for supporting analyses. Those details matter when interpreting whether the analyzed participants represent the randomized groups.
The registry lists planned enrollment of 120, with arm descriptions of 80 subjects assigned to the LT patch and 40 to placebo. The safety record instead lists 81 at risk in the LT patch group and 39 in the placebo group. These figures refer to different registry descriptions and should not be silently reconciled. The record does not explain the discrepancy.
Safety counts are reported separately from the primary immunogenicity outcome. The LT patch group lists 1 participant with a serious adverse event among 81 at risk, and the placebo group lists 2 among 39 at risk. The record also lists other adverse events for both groups. These counts are descriptive; without further information about event definitions, follow-up, exposure, and analysis, they do not establish a causal difference between treatment groups. Death counts are not reported in the registry record.
The registry also describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such planning illustrations are not observed power and are not a substitute for the trial’s results. Because the primary outcome has multiple time points and no single comparison is reported, a reader should not interpret the planning assumptions as evidence of a particular treatment effect.
9. Statistical Methods Explained
The registry identifies the study as randomized, double-blind, placebo-controlled, parallel-group, and quadruple-masked. Randomization is intended, in general, to reduce systematic differences between assigned groups at the start of a trial. Masking is intended to reduce the influence of treatment knowledge on participant experience, study conduct, and outcome assessment. These are general purposes of the design features; details of the randomization procedure, allocation concealment, and which parties were masked are not reported in the registry record.
What does GMT represent?
Geometric mean titer is a summary of antibody titers on a multiplicative rather than additive scale. In general, this can be useful when measured titers are positively skewed or vary substantially in magnitude. A typical calculation uses logarithms, summarizes the transformed measurements, and returns the summary to the original scale. That is a general description, not confirmation of the procedure used in this study; the registry record does not specify the calculation method, treatment of values below assay limits, or any adjustment for baseline values.
The outcome lists GMT and a 95% confidence interval. In general, a confidence interval reflects sampling uncertainty under a specified statistical model and procedure. It does not show the spread of individual participants’ titers, and it does not by itself establish that a difference is important. Interpreting it requires the estimate, the interval limits, and clarity about the comparison and analysis population. Those numerical results are not reported in the registry record.
Why are there several assessment days?
Immune responses are measured over time because an endpoint at one visit may not describe the same feature of response as an endpoint at another. The registry lists Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, and Day 194. Day 0 is the stated baseline assessment, while the other listed days form the follow-up schedule. The primary outcome title refers to measurements after the first and second vaccinations, but the registry does not give the timing of the vaccinations relative to every listed assessment or specify a model for the repeated measurements.
When multiple time points are examined, there may be several group comparisons rather than a single result. In general, making many statistical comparisons can increase the chance of at least one apparently unusual result under a null model. A prespecified strategy may address this through a hierarchy, an adjusted threshold, a selected primary time point, or another approach. Which approach was used, if any, is not reported in the registry record. The record explicitly does not reduce the primary outcome to one comparison.
What does the analysis population mean?
The Immunogenicity Evaluable Population is defined as subjects who were consented and randomized, received both assigned treatments, and had blood drawn for immunogenicity testing at baseline (Day 0) and at Day 21 and Day 35. This definition conditions inclusion on treatment receipt and completion of specified measurements. In general, an evaluable-population analysis can describe responses among participants with the required treatment and measurements, while an intention-to-treat analysis aims to retain participants according to randomized assignment. The registry does not state that an intention-to-treat analysis was conducted, nor does it provide another analysis-population definition.
Excluding participants without required measurements can affect the comparability created by randomization if missingness or treatment completion is related to participant characteristics or outcomes. A complete interpretation would benefit from counts screened, randomized, treated, and included in each analysis, alongside reasons for missing data and the chosen handling method. These details are not reported in the registry record. It is also not reported whether any imputation, sensitivity analysis, or baseline adjustment was used.
What can the safety counts tell readers?
The safety record separates serious adverse events from other adverse events and gives a number at risk and a number affected for each group. These are descriptive counts. In general, counts alone do not account for differences in follow-up duration, exposure, event recurrence, severity beyond the stated classification, or chance variation. They also do not establish that an event was caused by the assigned patch. The registry does not report a statistical comparison for these counts, event-specific time at risk, or an adjudication method.
The listed serious adverse event terms include percentages, but the registry excerpt does not identify the group denominators associated with each listed percentage. They should therefore be read as terms appearing in the record, not as a basis for reconstructing group-specific risks. Death counts are not reported in the registry record.
How should sample-size planning be read?
The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. In general, sample-size calculations depend on assumptions about the effect, variability, significance threshold, power, allocation, and analysis method. A planning illustration is not an observed treatment effect and does not show the power actually achieved after the trial. The registry does not report the trial’s original design calculation or its justification, and the planning illustration should not be treated as the trial’s own design.
Because this outcome includes multiple time points and the registry does not provide a single comparison, the planning assumptions cannot be linked to a particular reported GMT contrast from the registry record. The record lists 0 analyses, and numerical primary results are not reported in the registry record. Thus, the statistical methods that were actually applied to the endpoint, including model specification, confidence-interval construction, and multiplicity handling, remain unknown.
10. Multiplicity, Missing Data and Analysis Populations
The primary GMT outcome includes assessments at Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, and Day 194, and refers to immune responses after the first and second vaccinations. The registry states that the primary outcome has several categories or time points and was not reduced to one comparison. This means readers cannot identify a single prespecified contrast from the record as the sole primary result.
When a study examines multiple outcomes or time points, statistical multiplicity can arise. In general, if many comparisons are made, the chance of observing at least one result that appears statistically unusual can increase. Investigators may address this with a prespecified testing hierarchy, adjusted inference, or another strategy. The statistical plan and any multiplicity procedure are not reported in the registry record. The registry lists 8 outcome measures and 0 analyses, but does not give numerical results for the primary GMT outcome.
The primary analysis population requires receipt of both vaccinations and blood draws at Day 0, Day 21, and Day 35. The record does not report the number meeting that definition, the amount or pattern of missing data, reasons for missing assessments, or methods used to handle missing values. It also does not report whether all randomized participants were included in a separate analysis or whether sensitivity analyses assessed the effect of missing data.
Without the analysis population counts, missing-data approach, multiplicity plan, and endpoint results, it is not possible to evaluate how robust the primary inference is to exclusions or analytic choices. These omissions do not establish that the study lacked such procedures; they mean those details are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group 1: 37.5 µg LT Patch | 1 | 81 | 1.2% |
| Group 2: 0 µg LT Patch (Placebo) | 2 | 39 | 5.1% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1: 37.5 µg LT Patch | 79 of 81 |
| Group 2: 0 µg LT Patch (Placebo) | 32 of 39 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: 37.5 µg LT Patch | Group 2: 0 µg LT Patch (Placebo) |
|---|---|---|---|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | 0 of 81 | 1 of 39 |
| Non-cardiac chest pain | General disorders | 1 of 81 | 0 of 39 |
| Gastroenteritis | Infections and infestations | 0 of 81 | 1 of 39 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: 37.5 µg LT Patch | Group 2: 0 µg LT Patch (Placebo) |
|---|---|---|---|
| Application site erythema | Injury, poisoning and procedural complications | 72 of 81 | 14 of 39 |
| Application site rash | Injury, poisoning and procedural complications | 77 of 81 | 5 of 39 |
| Application site pruritus | Injury, poisoning and procedural complications | 72 of 81 | 8 of 39 |
| Application site discolouration | Injury, poisoning and procedural complications | 62 of 81 | 5 of 39 |
| Application site pain | Injury, poisoning and procedural complications | 22 of 81 | 3 of 39 |
| Diarrhoea | Gastrointestinal disorders | 11 of 81 | 4 of 39 |
| Upper respiratory tract infection | Infections and infestations | 7 of 81 | 4 of 39 |
| Application site oedema | Injury, poisoning and procedural complications | 11 of 81 | 0 of 39 |
| Blood glucose increased | Investigations | 6 of 81 | 3 of 39 |
| Protein urine present | Investigations | 4 of 81 | 3 of 39 |
Serious events with the highest arm-level rate: haemorrhoidal haemorrhage (2.6%), gastroenteritis (2.6%), non-cardiac chest pain (1.2%).
The registry lists serious adverse events by group using a number at risk and a number affected. In the 37.5 µg LT patch group, 1 participant had a serious adverse event among 81 at risk. In the placebo group, 2 participants had a serious adverse event among 39 at risk. The record also lists other adverse events for the groups: 79 among 81 at risk in the LT patch group, and 32 among 39 at risk in the placebo group.
These are descriptive registry counts, not adjusted comparisons. They do not indicate whether events were judged related to the patch, how long participants were followed for safety, whether events could recur in the same participant, or how serious-event reporting was defined. The registry lists Haemorrhoidal haemorrhage and Gastroenteritis at 2.6%, and Non-cardiac chest pain at 1.2%, as top serious terms; it does not specify group denominators for those percentages in this record. Death counts are not reported in the registry record.
The planned arm descriptions state 80 subjects for the LT patch and 40 for placebo, whereas the safety record gives 81 and 39 at risk. The registry does not explain this difference. The counts should not be interpreted as proof of a treatment-caused safety difference.
12. What the Result Does, and Does Not, Mean
The registry record establishes the study’s design and intended questions: randomized comparison of a two-vaccination LT patch regimen with placebo, with immune responses and safety as the focus. It specifies GMT as the primary immunogenicity measure, names a 95% confidence interval, and lists the assessment schedule. It also defines an Immunogenicity Evaluable Population based on receipt of both vaccinations and blood tests at required visits.
Those details explain what the study set out to measure, but they do not show the primary result. GMT estimates, confidence interval limits, and group comparisons are not reported in the registry record. Therefore, the posted information cannot establish the magnitude or precision of any immune-response difference, its pattern over time, or whether any comparison met a statistical criterion.
The safety counts describe participants recorded as affected by serious and other adverse events. They do not alone establish that an event was caused by the LT patch, and the registry does not give the follow-up or event-assessment detail needed for a fuller comparative interpretation. The listed serious-event terms also lack group-specific denominators in this record. The planned arm sizes and safety counts differ, without an explanation in the registry record.
The trial’s stated condition is prevention of travelers’ diarrhea, but the listed primary endpoint is immune response rather than a reported clinical illness outcome. The registry’s brief summary describes an evaluation of immune responses and safety. No result for prevention of travelers’ diarrhea is reported in the registry record, so the immunogenicity question should not be treated as equivalent to a demonstrated clinical effect.
Overall, the record supports a description of the trial’s intended comparison and selected safety counts. It does not support a conclusion about the size or clinical meaning of an immune response, nor a definitive comparative safety conclusion. Those judgments would require endpoint results, their uncertainty, fuller safety information, and the analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design information and outcome results need to be read separately. The registry specifies randomization, masking, a placebo comparator, a parallel-group structure, an immunogenicity endpoint, and an analysis-population definition. These details help frame the intended comparison. They do not, by themselves, provide evidence about the magnitude or precision of the outcome.
The primary endpoint is measured across several assessment days, and the registry explicitly does not reduce the outcome to one comparison. That matters because repeated measurements can produce a profile of responses rather than a single summary. Without a stated primary time point, a model for repeated measurements, or a multiplicity strategy, readers cannot tell how the investigators intended to prioritize or interpret the several possible comparisons. Those statistical details are not reported in the registry record.
The evaluable-population definition also illustrates a practical issue in trial analysis. Requiring both vaccinations and specified blood draws can make the endpoint interpretable among participants with the required observations, but the resulting population may differ from everyone randomized. Counts and missing-data methods are necessary to judge the consequences. They are not reported in the registry record.
Finally, the registry separates immunogenicity from safety and gives descriptive safety counts. Neither type of information can be substituted for the other: a GMT is an immune-response measure, while adverse-event counts describe reported harms. The record’s absence of primary numerical results limits any statistical inference, even though its design and outcome definitions are documented. This makes the distinction between a clearly stated research question and a reported result especially important.
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 does not report numerical GMT estimates, confidence interval limits, or comparisons between the LT patch and placebo groups. It also does not give results by assessment day, despite listing Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, and Day 194. As a result, the primary immune-response findings cannot be assessed for direction, magnitude, or precision.
The record does not report the statistical analysis plan, the model used for repeated measurements, baseline adjustment, assay handling rules, or a multiplicity procedure. The primary outcome spans multiple time points and is not reduced to one comparison. The number of participants in the Immunogenicity Evaluable Population and the handling of missing blood tests are not reported in the registry record.
The registry describes planned enrollment of 120 and arm sizes of 80 for the LT patch and 40 for placebo, while the safety counts at risk are 81 and 39, respectively. It does not explain the difference. The record also does not give detailed safety follow-up, event relatedness assessments, or group denominators for the listed serious-event percentages. Death counts are not reported in the registry record.
The registry lists secondary outcomes, including patch and skin-site residual LT and one-year immune responses in the LT patch group, but does not provide their results in this record. It also lists 0 analyses. These reporting gaps limit interpretation of both the planned endpoints and the available safety counts; they do not establish what analyses may have been conducted outside the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Traveler's Diarrhea (TD) Automated Process — NCT00751777.
- Registry record last updated 2020-01-29; status last verified 2020-01.
- 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.
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18. Record Summary
This completed randomized, double-blind, placebo-controlled Phase 2 study evaluated immune responses and safety after a two-vaccination regimen using an LT patch or placebo patch in healthy adults. It used a parallel-group design with quadruple masking. Planned enrollment was 120, with 80 subjects described for the 37.5 µg LT patch group and 40 for placebo.
The primary outcome was GMT with a 95% confidence interval, assessed on Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, and Day 194. The defined primary population required both vaccinations and blood draws at Day 0, Day 21, and Day 35. Primary numerical results and the statistical analysis plan are not reported in the registry record.
Safety counts are recorded, but the registry does not explain the difference between planned arm sizes and safety counts at risk. The record lists 8 outcome measures and 0 analyses.