Safety, Acceptability, and Feasibility of Enterade®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Acceptability, and Feasibility of Enterade® (NCT03782272), a randomized na study. The primary outcome is Frequency of Adverse Events or Serious Adverse Events.

2. Clinical Question

The study also set out to assess caregiver perceptions of acceptability and explore changes in markers of metabolism, gut dysfunction, systemic inflammation, and micronutrient status. Caregiver perceptions were designated qualitative, and the registry description says qualitative results will not be reported on ClinicalTrials.gov. The registry record does not include posted results for those objectives.

3. Trial Design

This was a randomized, parallel-group pilot study comparing AA-ORS with placebo. The record lists the allocation as randomized and the masking as triple. Its summary describes the study as double-blinded; the registry record does not specify which roles were masked, so the masking description cannot be reconciled further from the available information.

The study was conducted in Kakamega County, Kenya, and focused on children aged 12–24 months at risk for environmental enteric dysfunction. Its objectives covered safety during a 2-week course, feasibility and tolerability of dosing, caregiver acceptability, and exploratory biomarkers. The primary safety outcome had a timeframe of 0-21 days. The record gives an enrollment of 12, with 6 participants in the AA-ORS arm and 6 in the placebo arm.

The listed study start was 2019-02-26 and primary completion was 2019-03-20. The study status is terminated. The reason for termination is not reported in the registry record. The phase is listed as NA, and the sponsor is PATH.

This is a pilot study, and its stated aims emphasize safety, feasibility, and tolerability rather than a definitive comparison of clinical benefit. A small number of observed events can describe what occurred among enrolled participants, but it leaves limited information about how often such events might occur in a broader population. The registry record does not report a protocol rationale for the enrollment target or a sample-size justification.

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: This is the intention-to-treat population with all participants randomized and received at least one dose.

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 Frequency of Adverse Events or Serious Adverse Events, measured over 0-21 days.

The primary endpoint is the count of participants experiencing an adverse event or serious adverse event in the study-product and placebo arms through 21 days of follow-up. Assessment was described as based on physical or clinical examination. The unit is participants, so the outcome concerns whether participants experienced an event, not the total number of event episodes.

Safety outcomes are useful in an early pilot because they describe tolerability and identify events observed during exposure and follow-up. Counting participants with at least one event gives a direct, interpretable summary for each arm. It does not describe the event’s severity beyond the separate serious-event classification, its timing, duration, cause, or recurrence. Those details are not reported in the posted primary outcome.

In the reported primary result, 1 participant in the AA-ORS arm and 0 participants in the placebo arm had an adverse event or serious adverse event. The measure therefore describes the observed participant counts over the specified follow-up period. It does not, by itself, establish that an event was caused by the assigned solution or indicate how precisely the underlying event risk is known.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either had an adverse event or serious adverse event during the stated timeframe, or did not. The arm summaries are counts of participants with an event. This type of outcome is often reported with the number of participants who experienced an event and the number assessed in each group. Here, the registry record lists 6 participants in each arm and reports 1 event participant in AA-ORS and 0 in placebo.

What does an uncertainty interval add?

In general, a confidence interval expresses the uncertainty around an estimated effect or event frequency that arises because a study observes a sample rather than every person in the population of interest. A narrow interval indicates greater precision, while a wide interval indicates that a range of underlying values remains compatible with the data. An interval is not a guarantee about an individual outcome and does not resolve concerns about study conduct or generalizability.

No confidence interval is reported for the primary endpoint in the registry record. With sparse binary outcomes, an interval can be especially important: the observed counts alone do not show how uncertain the underlying event frequency is. The absence of an interval should not be interpreted as certainty, nor does it permit a conclusion that the groups are equivalent.

Why can a comparison be difficult with sparse events?

General statistical methods for binary outcomes compare the event experience between groups. Their usefulness depends on the pattern and amount of information in the data. When one or both groups have very few events, some standard calculations may be unstable or may not produce a meaningful estimate. The registry record indicates that values were missing or not estimable for a two-arm comparison of this binary endpoint. It does not state which method was attempted or give a comparison estimate. No specific test or model should therefore be inferred.

A descriptive contrast and an inferential comparison answer different questions. Counts describe what occurred in the enrolled groups. An inferential estimate attempts to characterize the degree to which the group difference could reflect sampling variation, subject to the model and assumptions used. The posted counts are descriptive; a formal comparison is not reported. The sponsor’s own analysis does not take precedence over a recalculation in this case because the record does not identify a discrepancy or provide a recalculated comparison.

What do the planning illustrations mean?

General sample-size planning uses assumptions about a target effect, significance level, allocation, and analysis method to illustrate how much information a future study might require. The planning description for this record specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For time-to-event outcomes, the description says the planning quantity is total events; for other outcomes, it is participants per arm.

These assumptions describe planning illustrations computed from the observed effect, not the design rationale for this trial. The registry record does not report numerical planning estimates in the available results or a prospective sample-size justification. Any such illustration is not observed power and does not establish that the pilot was adequately powered to test a treatment effect. A design based on an observed effect can be especially uncertain when the observed outcome is sparse.

What is over-dispersion, and does it apply?

In general, over-dispersion refers to more variability in count data than a statistical model expects. It can matter when analyzing counts of repeated events, because treating every event as independent may understate uncertainty if events cluster within participants. The primary endpoint is the count of participants with an event, rather than a reported count of all event episodes. The registry record does not report an over-dispersion assessment or an event-count model, so that issue cannot be evaluated for this result.

Interpretation also depends on outcome definitions, follow-up, and how missing observations are handled. The record defines the primary timeframe and population but does not report additional details about event adjudication, missing outcome data, or sensitivity analyses. General statistical methods cannot fill those reporting gaps.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("AA-ORS", "Placebo")
n      <- c(6, 6)
events <- c(1, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  AA-ORS  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Placebo  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures, but it posts no secondary results and lists no analyses. It does not report a multiplicity strategy, such as adjusting inference when several outcomes are tested. Without posted outcome-specific analyses or a stated statistical plan, it is not possible to determine whether multiple comparisons were planned or how they would have been handled. The primary safety count can be read descriptively without assuming a multiplicity adjustment.

The primary population is described as intention-to-treat and includes all participants randomized who received at least one dose. The record does not explain how this population was handled if a participant had missing safety information, nor does it report the extent or pattern of missing data. Methods for imputation, exclusion, or sensitivity analysis are not reported in the registry record. The observed counts should therefore be interpreted in the context of the stated population, without assuming how unreported data were treated.

The summary identifies caregiver acceptability as qualitative and says qualitative results will not be reported on ClinicalTrials.gov. No quantitative secondary results are posted for the exploratory biomarker objectives. The registry record also does not report a statistical analysis plan or interim analyses. These omissions limit assessment of prespecification and of how the primary result fits into the study’s full analysis strategy.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The primary safety outcome reports participants with an adverse event or serious adverse event during 0-21 days of follow-up. The AA-ORS arm has 1 participant with an event, while the placebo arm has 0. In the separate safety summary, serious adverse events are 0 in both arms; other adverse events are 1 in AA-ORS and 0 in placebo; deaths are 0 in both arms.

These are participant counts, not counts of repeated event episodes. The registry record does not list the adverse-event term or describe its clinical characteristics. It also does not attribute the event to the study product. The fact that no serious adverse events or deaths were recorded in either arm is a description of this pilot’s reported observations, not evidence that such outcomes cannot occur.

Because the number of participants is limited and the event count is sparse, the figures have limited precision. They are best read as a safety record for the stated population and follow-up, rather than as a precise estimate of risk or a definitive comparison between solutions.

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

The result documents that the registry record reports 1 participant with an adverse event or serious adverse event in the AA-ORS arm and 0 in the placebo arm during the specified follow-up. It also documents 0 serious adverse events and 0 deaths in each arm. Those observations address a narrow safety question within a pilot study.

The result does not establish that AA-ORS caused the reported event. The registry record does not give the event term, timing, severity beyond the serious-event classification, or an assessment of causality. It also does not report an inferential comparison or a measure of precision for the primary outcome. The observed arm counts alone cannot establish that the groups differ, are equivalent, or have the same underlying event frequency.

Nor do the safety counts answer the study’s other objectives. There are no posted secondary results for feasibility, tolerability, caregiver acceptability, or exploratory markers of metabolism, gut dysfunction, systemic inflammation, and micronutrient status. The registry description says qualitative caregiver results will not be reported on ClinicalTrials.gov. No conclusion about those outcomes can be drawn from the primary safety count.

The pilot’s stated purpose was to assess safety, acceptability, feasibility, and pediatric dosage or tolerability in children at risk for environmental enteric dysfunction. Its enrollment and sparse event pattern make the result a limited descriptive contribution, not a definitive evaluation of a clinical effect. No treatment recommendation or conclusion about effectiveness follows from the posted safety figures.

14. Why This Trial Matters Statistically

This trial illustrates how a clinically relevant safety outcome can be easy to state but difficult to estimate precisely when few participants and few events are observed. Counts of participants with an event are intuitive, yet they do not convey uncertainty on their own. Reporting an estimate with an uncertainty interval and a clearly described analysis would help readers understand how much the result can support beyond a description of the enrolled groups.

The registry record also demonstrates why outcome reporting needs to be interpreted against the study’s aims. Safety is the posted primary outcome, while feasibility, dose tolerability, caregiver acceptability, and biomarker changes were also objectives. The absence of posted secondary results means the safety finding cannot stand in for those other questions. Likewise, a listed outcome is not the same as a reported result or analysis.

For biostatisticians and clinical researchers, the trial highlights the value of making the target population, endpoint, timeframe, analysis population, missing-data handling, and comparison method explicit. The record defines some of these elements, including the follow-up and intention-to-treat population, but does not report a statistical analysis plan, missing-data approach, or formal primary comparison. Distinguishing descriptive counts from inferential conclusions is particularly important when outcomes are sparse.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The limited enrollment and sparse primary events constrain the precision and generalizability of the safety findings. The registry record reports 6 participants per arm, with 1 event participant in AA-ORS and 0 in placebo. It does not report a confidence interval or a formal comparison estimate, so uncertainty around the underlying event experience cannot be quantified from the posted result.

The record does not identify the reported adverse event, its timing, duration, or cause. It gives no further clinical detail about assessment or adjudication beyond physical or clinical examination. It also does not explain the reason for the terminated status. These missing details limit interpretation of both the event and the study’s completion.

Several planned objectives do not have posted results. Feasibility, tolerability, caregiver acceptability, and exploratory biomarkers cannot be evaluated from the primary endpoint. The registry description notes that qualitative results will not be reported on ClinicalTrials.gov, and secondary results are not posted.

Finally, the registry record does not report a sample-size justification, statistical analysis plan, missing-data methods, or multiplicity approach. The summary describes the study as double-blinded, while the design entry lists triple masking; the roles masked are not specified. These reporting limitations prevent a fuller assessment of the design and analysis, beyond the narrow descriptive safety findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Acceptability, and Feasibility of Enterade® — NCT03782272.
• Registry record last updated 2021-02-04; status last verified 2020-07.
• Results first posted 2021-02-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT03782272 is a randomized, parallel-group pilot study of Enterade® in children at risk for environmental enteric dysfunction in Kakamega County, Kenya. It compares AA-ORS with placebo and lists triple masking, while the study summary describes double-blinding. The record reports enrollment of 12 and a primary safety endpoint covering 0-21 days.

The posted primary result records 1 participant with an adverse event or serious adverse event in AA-ORS and 0 in placebo. Serious adverse events and deaths are reported as 0 in each arm. The record lists 14 outcome measures but no secondary results and no analyses. Study status is terminated; the reason is not reported in the registry record.

The finding is descriptive and does not include a confidence interval or formal comparison. It should be interpreted as a limited account of observed safety events in this pilot, not as a definitive estimate of risk or a result about efficacy.