A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children (NCT02435069), a randomized phase 4 study. The primary outcome is Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen.

2. Clinical Question

3. Trial Design

The registry describes a completed randomized, unmasked crossover study. It is listed as Phase 4, sponsored by Nemours Children's Clinic, and has an enrollment of 5. The study began on 2016-02-09 and its primary completion date is 2017-03-28. Because this was a within-subject comparison, participants received the regimens in randomized treatment sequences; the same participant could contribute information under both regimens.

The registry describes a pre-operative baseline phase in which fecal soiling and abdominal pain were recorded for a minimum of 2 weeks before surgical construction of the ACE stoma. Baseline stool calprotectin and serum electrolytes were also collected, although the registry description is truncated. During the first intervention, the starting regimen was randomized between NS and USP glycerin. The record specifies starting amounts of 10mL/kg for NS and 20 mL for glycerin, administered every other day. It says the NS dose was titrated in 10 mL increments, but the intervention description is incomplete.

A subsequent effectiveness phase evaluated both solutions at optimal dosing and administration frequency after continence was achieved with minimal side effects. The registry lists secondary outcomes concerning dosing frequency, flush volume, electrolyte abnormalities, stool calprotectin, cramping, and vagal symptoms. The posted primary results describe continence counts. Further details about sequence implementation, washout, adherence, and the statistical plan 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.

Before assignment: 9 assessed for eligibility, 4 excluded (3 did not meet inclusion criteria and 1 surgery date significantly delayed), 5 consented and randomized to treatment sequence in dosing phase (3 started on saline followed by USP Glycerin, 2 started on USP glycerin followed by saline).

Preoperative Baseline Phase

Dose Response - First Intervention

Reasons for not completing this period:

Effectiveness - Second Intervention

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The data from a total of 5 participants were analyzed for each arm of the study.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen, measured over Data collection started following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days..

The primary endpoint is the number of participants recorded as having gained and maintained continence on each flushing regimen. The registry defines fecal soiling as non-toilet elimination and says parents or children documented events directly, tallying pairs of underwear or protective undergarments soiled with stool per day. The outcome measure therefore starts with daily soiling observations and reduces those records to a participant-level continence count.

The registry says data collection began following consent and procedural training, was collected daily from day 1, and continued for the duration of the study, an average of 135 days. The primary outcome uses the last data point in the final phase for both NS and USP glycerin. This offers a clinically interpretable summary of the number of participants who met the study's continence assessment under each regimen. However, the posted description does not state the precise threshold or duration of stool-free observation required to classify a participant as continent. The primary results are counts, not daily soiling trajectories or a quantified within-participant contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary primary outcome: whether a participant was counted as continent on a regimen. For a binary outcome, each participant is classified into one of two categories for the relevant endpoint, and results can be summarized as counts or proportions. The posted results give counts. No percentages should be inferred from them unless those values are explicitly reported, and no inferential comparison is posted for this endpoint.

Why does the crossover design matter?

In a crossover study, participants receive more than one treatment condition, so each person can serve as their own comparison. This can account for stable participant characteristics that might otherwise differ between separate groups. But the statistical analysis must preserve the pairing: outcomes observed for the same participant are related, not independent. A simple comparison treating every regimen observation as unrelated could misrepresent uncertainty. For a binary endpoint, the pattern of paired outcomes is important. The registry reports the separate regimen counts but does not report the participant-level pairing pattern or a paired analysis.

What does a confidence interval communicate?

In general, a confidence interval describes the range of effect values compatible with the data and the method used to calculate it. It communicates precision as well as the direction and magnitude of an estimate. A wide interval signals considerable uncertainty, while a narrower interval signals greater precision under the model. No confidence interval for the primary comparison is reported in the registry record. Without one, readers cannot use the posted primary result to assess the precision of a comparative effect estimate.

Why is no two-regimen test reported?

The record states that values were missing or not estimable for a two-arm comparison of the binary endpoint. That means the posted results do not include an inferential test for the primary comparison. The registry does not explain the specific computational or data limitation behind that status. It would therefore be inappropriate to reconstruct a test from the marginal counts alone, particularly because the design is crossover and the paired participant-level outcomes are not shown.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrated effect is defined as a stated fraction of the observed effect. Such calculations are planning scenarios, not observed power and not evidence that the completed study had a particular probability of detecting an effect. A planning estimate depends on its assumptions and should not be treated as a trial result. The registry record does not report a design justification or explain whether these illustrations informed the trial's original enrollment target.

Why can over-dispersion matter in count outcomes?

In general, over-dispersion means that count outcomes vary more than a statistical model expects. When present, a model that assumes less variability can produce uncertainty estimates that are too small. The primary endpoint is a participant-level binary count, while the underlying daily soiling measure is a repeated count of soiled garments. The registry does not report a model of daily counts or an assessment of over-dispersion. This general issue should not be mistaken for a finding about these data.

Overall, the posted primary analysis is descriptive. General statistical principles help explain what paired analyses, confidence intervals, and planning illustrations mean, but they do not supply missing participant-level data or replace the analysis not reported in the registry record.

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("Subjects Continent on NS Antegrade Flush", "Subjects Continent on USP Glycerin")
n      <- c(5, 5)
events <- c(1, 4)
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  Subjects Continent on NS Antegrade Flush  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  Subjects Continent on USP Glycerin  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 4 analyses, and reports 6 secondary outcomes. The posted information does not describe how the study addressed multiplicity, such as whether one outcome was designated as the sole confirmatory test or whether any adjustment was planned for testing multiple outcomes. Without that information, results across several outcomes should not be treated as if each were an isolated test with no risk of chance findings.

The primary outcome is reported as descriptive counts, and a two-arm inferential comparison is marked as missing or not estimable. The record does not provide a participant-level dataset, a reason for the unavailable comparison, or an alternative analysis. It also does not report the statistical analysis plan, analysis-population definitions beyond the stated primary outcome population, or how missing daily records and incomplete follow-up were handled.

The study's crossover design makes the analysis population and paired observations relevant. The registry states that data from a total of 5 participants were analyzed for each arm, but does not explain whether every participant contributed complete data under both regimens or how partial observations were treated. The method used to address treatment sequence, period effects, or possible carryover is not reported in the registry record. These omissions limit assessment of both the primary comparison and the secondary analyses.

Missing analysis details are not evidence that a particular method was or was not used. They mean that readers cannot verify the handling of multiplicity, missing observations, or the paired structure from the registry record alone.

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 listed safety outcome concerns vagal symptoms with flushing. For serious events, the registry reports 0 affected participants among 5 at risk with NS and 0 among 5 at risk with USP glycerin. The death count is 0 for each regimen. These are the serious-event and death figures reported for the listed groups; they do not establish that every possible harm was assessed or that no unlisted event occurred.

For the other-event fields, the registry reports 0 affected participants among 5 at risk with NS and 1 among 5 at risk with USP glycerin. These figures should be kept distinct from the serious-event counts: the other-event field records a vagal symptom outcome, while the serious-event field reports serious events. The registry does not provide additional detail about the symptom, its severity, timing, or relationship to treatment.

Safety counts in a small study describe what was recorded among participants at risk. They do not provide a precise estimate of how often an event would occur in a larger population. The absence of a recorded serious event in these groups is not proof that a regimen has no serious risks. The registry record does not report further serious-event terms.

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

The main result is a descriptive contrast in recorded continence counts: 1 participant was recorded as continent on NS, and 4 were recorded as continent on USP glycerin. The registry reports 5 participants analyzed for each arm. In a crossover study, these are regimen-specific counts from participants who may contribute observations under both conditions, not counts from independent treatment groups.

The result does not show the individual paired outcomes, so it is not possible to tell from the posted counts how many participants had the same outcome on both regimens or changed outcome between them. Nor is there a reported inferential comparison or confidence interval that quantifies the uncertainty in the regimen contrast. The finding should therefore not be read as a precise estimate of a causal effect or as a result that necessarily applies to other children.

The primary endpoint captures continence as classified from daily stool-soiling records in the final phase. It does not, by itself, summarize flush burden, side effects, electrolyte changes, colon health, or the full pattern of daily symptoms. Although the registry lists secondary outcomes addressing some of those topics, the primary count alone cannot answer them.

Overall, the posted result documents the observed endpoint counts in this study. It does not establish that one regimen is generally more effective or safer, and it is not a substitute for the unreported paired analysis and fuller outcome information. The clinical meaning remains bounded by the small enrolled group, the registry's endpoint definition, and the analysis details not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it uses a within-subject comparison rather than assigning separate groups to the two regimens. Crossover designs can make efficient use of observations by comparing treatment conditions within the same participant. Their advantage depends on collecting and analyzing the paired outcomes appropriately. Separate regimen counts do not reveal the paired pattern needed to understand how participants' outcomes changed across conditions.

The study also illustrates the distinction between a clinically direct summary and an inferential comparison. A count of participants classified as continent is easy to interpret, but the count alone does not describe precision or uncertainty. The registry explicitly marks the two-arm comparison as missing or not estimable, leaving the primary result descriptive rather than inferential.

Finally, planning illustrations based on observed effects are not the same as observed power and are not proof that a completed study was adequately sized for its aims. The registry's planning assumptions can frame hypothetical future planning, but the record does not report the original design justification. Taken together, the design and reporting make this a useful example of why crossover structure, paired data, endpoint definitions, and transparent analysis details matter when interpreting clinical trial results.

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 primary limitation is the small enrollment: the registry reports an enrollment of 5 and data from a total of 5 participants analyzed for each arm. With so few participants, the posted counts provide limited information about variability across children and cannot support a precise population-level comparison. The registry does not report a confidence interval or an inferential test for the primary endpoint.

The primary endpoint description gives the daily soiling measure and says the final phase data point was used, but the exact operational threshold for continence is not reported. The record also does not show each participant's outcome under both regimens. That limits interpretation of the crossover comparison and prevents examination of the paired response pattern.

The trial was unmasked, and the registry does not report whether outcome assessors were masked. Soiling was documented by parents or children through direct event recording, which makes the endpoint dependent on recorded observations. Further details on adherence, missing daily records, treatment sequence implementation, washout, period effects, and carryover are not reported in the registry record.

The registry describes dose adjustment and an effectiveness phase, but the posted intervention descriptions are incomplete. It does not provide enough detail to assess all dose and administration decisions. It also lists secondary safety and health outcomes without providing their full results in the primary outcome information. These limits constrain interpretation to the specific descriptive result that is posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children — NCT02435069.
• Registry record last updated 2019-08-28; status last verified 2019-08.
• Results first posted 2019-08-22.
• 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

The registry record describes a completed Phase 4 randomized, unmasked crossover study sponsored by Nemours Children's Clinic, with enrollment of 5. It compared antegrade flush regimens using normal saline and USP glycerin in children with intractable fecal incontinence. The primary outcome was the number of participants who gained and maintained continence on each regimen, based on daily soiling records and the final phase data point.

The posted primary counts are 1 participant continent on NS and 4 on USP glycerin, with a total of 5 participants analyzed for each arm. A two-arm comparison for the binary endpoint is marked missing or not estimable. The record also lists secondary outcomes involving dosing, adverse symptoms, electrolytes, and stool calprotectin. Interpretation is limited by the small enrolled group, the absence of a reported inferential comparison, and missing details about paired outcomes and analysis procedures.