Live Attenuated ETEC Vaccine ACE527 With and Without dmLT Adjuvant in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Live Attenuated ETEC Vaccine ACE527 With and Without dmLT Adjuvant in Adults (NCT01739231), a randomized phase 1, phase 2 study. The primary outcome is Part A: Number of Serious Adverse Events and Adverse Events Leading to Withdrawal.

2. Clinical Question

This is a randomized, quadruple-masked, parallel study with Phase 1 and Phase 2 components. Its two-part structure matters when interpreting the posted results: Part A focused on vaccination, while Part B involved challenge with ETEC H10407. The listed Part B safety groups should not be treated as if they were all part of the Part A primary endpoint. The record describes the study as completed, but completion alone does not establish that every planned outcome or analysis is available in the registry. The page therefore distinguishes the stated endpoint, the safety counts that are posted, and questions for which a result is not reported in the registry record.

3. Trial Design

The study is listed as randomized, quadruple-masked, and parallel, with Phase 1 and Phase 2 components. Its stated enrollment is 81. The study had two parts with different purposes. Part A examined the vaccine alone, the vaccine with dmLT, and placebo. The registry summary says that about 60 healthy adults were expected to participate in Part A and describes the study as investigating safety, tolerability, and immune response. Part B examined the vaccine regimens in the setting of an ETEC H10407 challenge.

In Part A, participants received three oral doses at 0, 1, and 2 months. The arm descriptions say enrollment of a second cohort depended on the safety profile of the first cohort. That is a design feature reported in the record; details about how safety findings were evaluated to make that decision are not reported in the registry record. The summary describes participants staying at the research facility for several nights for the first dose, with no overnight stay required for the second and third doses.

Part B included eligible participants from Part A who expressed interest, as well as volunteers who had not been vaccinated in Part A. The record describes a Part B-only control group and says its results are combined with those of the Part A placebo control. This makes the flow from Part A to Part B relevant: the groups in the challenge phase are not simply the same set of participants as the vaccination groups. Full details of eligibility, participant flow, and the analysis populations are not reported in the registry record.

The listed outcomes include shedding measures and several summaries of diarrhea and stool output after challenge. The registry record lists 53 outcome measures, but it does not report a single analysis for the primary endpoint in the posted analysis section. The statistical plan, sample-size justification, and any interim analyses 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.

Part A

Part B

Analysis population for the primary outcome, as defined in the registry: Participants in Part A of the study who received at least one dose of the study product.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part A: Number of Serious Adverse Events and Adverse Events Leading to Withdrawal, measured over up to 1 month after last vaccination (3 months).

The stated primary endpoint is the number of serious adverse events and adverse events leading to withdrawal in Part A. It applies to participants who received at least one dose of study product, and the specified observation period is up to 1 month after the last vaccination (3 months). Unsolicited adverse events were collected throughout Part A, graded for severity, and assessed for relationship to vaccine. Whether an adverse event led to withdrawal was determined at the discretion of study staff.

Safety endpoints of this kind are used to describe harms observed during a study and to identify events that require attention in interpreting the intervention experience. Serious events and events leading to withdrawal are distinct concepts: an event can be serious without leading to withdrawal, and withdrawal depends on the study staff's determination described in the endpoint definition. The registry record does not provide a breakdown of the primary endpoint into those components by Part A arm, nor does it give a statistical comparison for the endpoint. The available adverse-event group summaries should therefore be read as posted safety figures, not as a complete analysis of every part of the stated primary endpoint.

The outcome is a count, not a measure of immune response or protection against challenge. The study's other objectives and outcomes address those different questions, including shedding and diarrhea after challenge. Results for those outcomes are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is described as randomized, quadruple-masked, and parallel. Randomization is intended to support fair allocation to study groups, while masking is intended to limit the influence of treatment knowledge on participants, staff, or assessments. These are general purposes of those design features; the registry record does not report further details about the randomization procedure or exactly who was masked. A parallel design means groups receive their assigned regimens rather than crossing over between them, but the record's two-part structure still needs to be considered when reading group results.

What a count outcome conveys

The primary outcome is framed as a number of events, and the posted safety groups give affected counts and group sizes. A count is directly interpretable as a tally within the stated group, but a tally alone is not an adjusted comparison. It does not account for differences in follow-up, participant characteristics, or how the study handled repeated events. Those analysis details are not reported in the registry record. In particular, the posted summaries should not be taken as a complete account of event timing, severity categories, or withdrawals unless those details are separately reported.

For a comparative analysis, researchers might use methods suited to the outcome definition and study design. The appropriate choice depends on whether the endpoint counts participants with at least one event, counts every event, or uses another construction. That specification, the planned statistical model, and any adjustment strategy are not reported in the registry record. It would therefore be inappropriate to infer a particular model from the endpoint title or the available group counts.

Uncertainty and precision

In general, a confidence interval describes a range of values compatible with the data and the method used to calculate it. A narrow interval indicates greater precision than a wide interval, while an interval spanning a broad range of plausible effects signals substantial uncertainty. The registry record does not report a confidence interval or a comparative estimate for the primary endpoint. The posted counts alone cannot replace those quantities. Small group counts can also leave uncertainty about event frequencies, especially for uncommon outcomes; this is a general statistical concern, not an additional result from this study.

A p-value, in general, measures how compatible the observed data are with a specified null model under the assumptions of a statistical test. It does not measure the probability that a treatment works, and it does not describe the size or clinical importance of an effect. No p-value for the primary endpoint is reported in the registry record. There is consequently no inferential test result to interpret for that endpoint.

Several outcomes and comparisons

The record lists 53 outcome measures, covering safety and other questions such as shedding and challenge outcomes. When many outcomes or comparisons are examined, the chance of finding an apparently unusual result can increase if each is assessed independently without a prespecified strategy. General approaches to this issue include defining a hierarchy of outcomes or adjusting interpretation for multiple testing. The registry record does not report whether either approach was used, what outcomes were prioritized beyond the stated primary endpoint, or how multiplicity was addressed.

The primary endpoint itself combines serious adverse events and adverse events leading to withdrawal. Those components may have different meanings and frequencies. The endpoint definition states that withdrawal due to an adverse event was determined at the discretion of study staff. The record does not report separate component results or an analysis plan explaining how the combined outcome was constructed. This limits what can be inferred from a group-level serious-event summary.

Planning illustrations are not trial results

The sample-size section is described as a planning illustration based on an observed effect, with equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation. Its rows describe planning for specified fractions of the observed effect. Those illustrations are hypothetical planning quantities, not participants actually enrolled in a comparison and not observed power. The record does not report the trial's own sample-size justification, and no calculation from the planning illustration can establish that this trial had adequate power for its outcomes. Any sample-size values shown in the generated section should be interpreted as illustrative rather than as an account of the original trial design.

Overall, the registry record supports a descriptive reading of the posted safety counts. It does not supply the comparative estimates, precision measures, or analysis details needed for a full inferential interpretation. A more complete methods assessment would require the protocol or statistical analysis plan and results that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 53 outcome measures, including the Part A safety outcome and secondary outcomes concerning shedding, diarrhea, and stool output. A large set of outcomes creates a multiplicity question: if many hypotheses are tested, some results may appear notable by chance. As a general matter, a trial can address this by prespecifying a hierarchy, limiting confirmatory comparisons, or adjusting inference. Which, if any, approach was used is not reported in the registry record. The record also does not report a complete statistical analysis plan or identify a multiplicity strategy for the listed outcomes.

Missing-data handling is not reported in the registry record. The available information does not describe how participants who withdrew, missed assessments, or lacked outcome measurements were handled, or whether any imputation or sensitivity analysis was used. Participant flow into the challenge phase and the exact analysis populations are also not fully. These omissions matter because the interpretation of a count or comparison depends on who was included and how unavailable outcomes were treated.

The primary endpoint definition specifies participants who received at least one dose and a follow-up period up to 1 month after the last vaccination (3 months). However, the record does not provide a separate primary-endpoint analysis by Part A group or an explanation of how the serious-event and withdrawal components were combined. It reports 0 analyses in the posted analysis information. Therefore, there is no reported primary-endpoint estimate, interval, or test to assess alongside the multiplicity and missing-data questions. The absence of these details is not evidence that a particular method was or was not used; the method is simply not reported in the registry record.

11. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fractured right wrist (8.3%).

The serious-event figures are reported separately for Part A and Part B. In Part A, the listed counts are 0 of 24 for ACE527 alone, 0 of 24 for ACE527 plus dmLT, and 0 of 12 for placebo. In Part B, the counts are 1 of 12 for ACE527 alone, 0 of 12 for ACE527 plus dmLT, and 0 of 31 for control. The listed groups each show 0 deaths. These are the figures in the posted safety summary; they should not be combined across parts because the groups and study context differ.

A count of 0 in a group means no event is listed for that group in the registry summary. It does not prove that the underlying risk is zero, and it does not establish equivalence between groups. Conversely, the Part B count of 1 does not establish a causal relationship to vaccination. The registry record does not report a comparative statistical analysis, a confidence interval, or a detailed attribution analysis for these figures. It notes a serious-event term, “Fractured Right Wrist,” at 8.3%, but does not provide enough detail to link that term to a particular group or draw a causal conclusion.

The stated primary endpoint also includes adverse events leading to withdrawal. The available group summary does not separately show those withdrawals. It should not be treated as a complete breakdown of the primary endpoint.

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

This record describes a randomized study of ACE527, alone or with dmLT, with a vaccination phase and a challenge phase. The posted adverse-event summaries show the serious-event counts by listed group, as well as counts for other adverse events. They provide a descriptive view of safety reporting, but they do not provide an inferential comparison or a precision estimate for the primary endpoint.

The record does not report the study's primary-endpoint analysis, a statistical test, or a confidence interval. It also does not report results for the listed challenge outcomes, including diarrhea measures. Accordingly, the safety figures cannot answer the separate question of whether a vaccine regimen affected illness after challenge. The study's broad purpose in the summary is not a substitute for posted outcome results.

Nor do the available counts establish that one regimen is safer or less safe than another. Differences in raw counts, if noticed, are not adjusted for design or follow-up and are not accompanied by a reported analysis. The record does not give enough detail to evaluate event attribution, withdrawals, missing outcomes, or the handling of multiple outcomes. These limitations constrain interpretation; they do not show that the study was necessarily conducted or analyzed in a particular way.

The responsible conclusion is narrow: the registry record documents the study design and posts group-level safety counts, but it does not report the comparative analysis needed to quantify uncertainty around the primary endpoint. The listed events and the absence of listed events should be understood as observations in the registry summary, not as proof of absence of risk or proof of a treatment effect. Results not reported in the registry record remain unknown from this record.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its questions and populations span distinct study parts. Part A concerns vaccination and safety, while Part B introduces an ETEC H10407 challenge and includes participants who may have entered from Part A as well as volunteers who had not been vaccinated there. The registry also describes a Part B-only control whose results are combined with the Part A placebo control. Understanding those relationships is essential before interpreting any group comparison.

The record illustrates why an endpoint definition and a result are not the same thing. The primary endpoint is defined as a number of serious adverse events and adverse events leading to withdrawal, with a specified population and follow-up period. Yet the registry's posted analysis information lists 0 analyses, and the available group summaries do not give a complete breakdown of that combined endpoint. A clear definition supports interpretation, but it cannot replace an estimate, uncertainty interval, and documented analysis.

The breadth of the outcome list also raises an important general statistical issue: many outcomes can make selective emphasis difficult unless priorities and analysis methods are clear. The record lists 53 outcome measures, but does not report the statistical plan or multiplicity strategy. It also does not report how missing data or analysis populations were handled. These are not minor technical details; they affect how confidently readers can interpret reported results.

Finally, the distinction between descriptive safety counts and evidence from a comparative analysis is central. Counts can document what the registry reports, but without the accompanying analysis they cannot establish the size, precision, or causal interpretation of a difference. This page makes that distinction explicit rather than treating the presence of numerical safety data as a complete statistical result.

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 most important limitation for interpreting this trial from the registry record is the lack of a reported primary-endpoint analysis. The outcome is defined, and group-level adverse-event summaries are available, but the record does not provide a comparative estimate, confidence interval, or test for the primary endpoint. The posted analysis information lists 0 analyses. Therefore, the safety counts can be described but not used to make a precise comparison.

The safety summaries do not fully align with every element of the stated primary endpoint. The endpoint includes serious adverse events and events leading to withdrawal, while the available group figures do not separately report withdrawals. The record does not show whether the counts represent participants with events, total events, or another analysis construction beyond the labels in the summary. The serious-event term list also does not give enough context to assign the term to a specific group or assess causality.

The study has separate vaccination and challenge phases, with distinct groups and a control description that combines Part B-only participants with the Part A placebo control. Full participant flow and analysis populations are not reported in the registry record. Without those details, it is difficult to assess the comparability and precise composition of each reported group.

The registry record lists many outcome measures but does not report the statistical plan, multiplicity strategy, missing-data methods, interim analyses, or the trial's sample-size justification. Challenge outcomes and immune-response results are not reported. These gaps limit assessment of both the safety endpoint and the study's broader objectives; they should not be filled by assuming methods or results that the record does not state.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Live Attenuated ETEC Vaccine ACE527 With and Without dmLT Adjuvant in Adults — NCT01739231.
• Registry record last updated 2019-02-12; status last verified 2019-01.
• Results first posted 2018-12-21.
• 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

The registry record describes NCT01739231 as a completed randomized, quadruple-masked, parallel Phase 1 and Phase 2 study with enrollment of 81. It examined oral ACE527 alone and with dmLT, with placebo in Part A and an ETEC H10407 challenge in Part B. The primary outcome was the number of serious adverse events and adverse events leading to withdrawal in Part A, among participants who received at least one dose, through up to 1 month after the last vaccination (3 months).

Posted safety summaries give serious-event counts for the listed Part A and Part B groups and show 0 deaths in each listed group. The record lists 53 outcome measures but 0 analyses in the posted analysis information. A comparative primary-endpoint result, statistical plan, missing-data methods, and results for the challenge outcomes are not reported in the registry record. The available figures therefore support descriptive safety reporting, not a full inferential assessment of the trial's questions.