Fecal Microbiota Transplant (FMT) in Pediatric Active Ulcerative Colitis and Pediatric Active Crohn's Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fecal Microbiota Transplant (FMT) in Pediatric Active Ulcerative Colitis and Pediatric Active Crohn's Colitis (NCT02330653), a randomized phase 1, phase 2 study. The primary outcome is 1. Safety and Tolerability of Universal Donor FMT Compared to Placebo: FMT-related Adverse Events Grade 2 or Above.

2. Clinical Question

The study also had secondary objectives concerning remission, inflammatory biomarkers, donor microbiome presence, and improvement in disease activity. Its stated primary aims were to assess safety and tolerability, rather than to establish a treatment effect on disease activity. The posted primary result is therefore best read as an event count in the assessed participants, not as a comparative estimate of clinical benefit.

The registry record describes a mixed population with active ulcerative colitis or Crohn’s colitis. Separate outcome counts by diagnosis are not reported in the registry record. Nor is a diagnosis-specific result available for interpreting whether the event counts differ between these conditions.

3. Trial Design

This was a Phase I/II, randomized, placebo-controlled, single-center study with a parallel-group design and quadruple masking. The registry record reports enrollment of 15. The study status is completed; its recorded start was 2015-11, and primary completion was 2019-04-08.

The intervention was universal donor FMT, compared with placebo. The FMT arm description specifies a retention enema during the first week, followed by once-weekly administration of 15 capsules for 7 weeks; the capsules were described as equivalent to 7.5 grams of human stool and administered within 60 minutes of thawing. The placebo description likewise specifies an induction placebo enema followed by once-weekly administration of 15 placebo capsules for 7 weeks. The description of what happened after the blinded treatment period is incomplete in the registry record, so further treatment details are not reported in the registry record.

Randomization assigns participants to study arms by chance, while masking is intended to limit knowledge of assignments during study conduct and assessment. Those design features can reduce some sources of bias, but they do not themselves establish that the arms were comparable in every respect or that the outcome counts are precise. The registry record does not report the randomization sequence method, allocation concealment details, or the specific roles covered by quadruple masking.

The primary endpoint population is described as participants who received FMT or placebo, completed the study, and had follow-up data available. The posted primary counts use 8 participants in the FMT arm and 5 in the placebo arm. Those arm counts do not match the overall enrollment figure; the reasons participants are absent from the primary outcome population 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: Participants who received FMT or placebo, completed the study, and follow up data is available.

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: There were two participants that were removed from the study after providing informed consent but before receiving any treatment. As a result, these participants were not included in the analysis and were not followed for adverse events.

6. Primary Endpoint

The registry lists the primary outcome as 1. Safety and Tolerability of Universal Donor FMT Compared to Placebo: FMT-related Adverse Events Grade 2 or Above, measured over At 8 weeks after start of FMT up to 6 months post treatment, an average of 10 months.

The primary endpoint counts participants with FMT-related adverse events of Grade 2 or above. It is a count outcome: the posted values are 4 participants in the FMT arm and 0 in the placebo arm. The record describes the endpoint as the number of participants with qualifying events in each arm, rather than the total number of events.

The assessment period is described as beginning 8 weeks after start of FMT and extending up to 6 months after treatment, with an average of 10 months. The population is limited to participants who received their assigned study treatment, completed the study, and had follow-up data available. This definition matters: the counts do not represent everyone enrolled, and they should not be treated as an intention-to-treat result without further information.

Safety and tolerability endpoints are used in early-phase trials to record unwanted effects during and after exposure to an intervention. A Grade 2-or-above threshold focuses the endpoint on events meeting that stated severity criterion, but the grade threshold does not by itself describe the event’s cause, duration, or clinical consequences. In this endpoint, the events are specifically labeled FMT-related. Details of how relatedness was judged, how severity was graded, and how events were collected are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a binary participant-level endpoint: each participant either had at least one qualifying FMT-related adverse event of Grade 2 or above during the assessment period, or did not. The summary is a count of participants in each arm. It is not an event rate per unit of follow-up, and it does not convey how many qualifying events an affected participant experienced.

What does a count show?

A count is a direct description of the number of participants meeting the endpoint definition. Reading the count requires its denominator and the population definition. Here, the primary endpoint population consists of participants who received FMT or placebo, completed the study, and had follow-up data available. The posted counts are 4 of 8 in the FMT arm and 0 of 5 in the placebo arm. These figures describe the observed endpoint population; they should not be generalized automatically to all enrolled participants or to a broader clinical population.

For a binary outcome, analysts may compare arms using a difference in proportions, a relative measure, or a model-based estimate. Such a comparison needs a clearly defined analysis population and an appropriate method. The registry record does not report an estimable two-arm comparison for this endpoint, and it reports no analysis results. No comparative estimate or p-value should therefore be read into the raw counts.

Why does uncertainty matter?

In general, a confidence interval gives a range of values compatible with the data and the statistical method, under its assumptions. It expresses uncertainty in an estimate; it is not a guarantee that the true value lies within the interval. With small participant groups, uncertainty can be substantial, particularly when one arm has no observed events. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be quantified from the posted outcome counts alone.

In general, a significance test evaluates how compatible data are with a specified null hypothesis under a model. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. No primary-endpoint test result is reported in the registry record. The observed counts should not be described as statistically significant or statistically non-significant.

What role do the planning illustrations play?

Planning illustrations are not observed trial outcomes and are not a measure of the trial’s achieved power. The registry-based illustrations are described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect specified as a fraction of the observed effect. For non-time-to-event outcomes, the reported planning quantity is participants per arm. No numerical planning values are reported in the registry record details used for this analysis. Such illustrations depend on assumptions and should not be treated as the study’s original sample-size justification; that justification is not reported in the registry record.

In general, power is the probability that a study would reject a null hypothesis under a particular assumed effect and analysis plan. It is not a probability that the observed result is correct. Retrospective calculations based on an observed effect are especially dependent on the unstable effect estimate from a small study. The registry record does not report the trial’s own sample-size justification or a prespecified power calculation.

How should safety summaries be separated?

The primary endpoint counts participants with FMT-related events meeting a severity threshold. The separate adverse-event summary includes serious events and other events, with its own at-risk denominators. In general, a serious adverse event is a safety category distinct from an event classified by a severity grade; the terms should not be treated as interchangeable. The registry record does not provide enough detail to reconcile all safety populations or to determine how each listed event maps to the primary endpoint.

The record reports no analyses for the listed outcome measures. Statistical methods beyond the design description and planning assumptions, including the prespecified comparison method, adjustment variables, confidence-interval method, and interim analysis procedures, are not reported in the registry record. Those omissions limit reconstruction of the intended analysis and interpretation of any unreported comparisons.

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("Fecal Microbiota Transplant (FMT)", "Placebo")
n      <- c(8, 5)
events <- c(4, 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  Fecal Microbiota Transplant (FMT)  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8
ARM  Placebo  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four secondary outcomes: remission of disease, improvement in inflammatory biomarkers, percentage of donor microbiome present in the transplant recipient, and number of participants with improvement in disease activity. It reports five outcome measures overall, but numeric results for these secondary outcomes are not reported in the registry record among the registry entries. The record reports zero analyses.

Multiplicity arises when several outcomes or comparisons are assessed. In general, the more statistical tests conducted, the greater the chance that at least one result may appear noteworthy by chance if no adjustment or prespecified hierarchy is used. Whether and how multiplicity was addressed is not reported in the registry record. The secondary outcomes should therefore be treated as objectives listed in the record, not as evidence of a demonstrated effect.

For the primary endpoint, the analysis population is described as treatment recipients who completed the study and had follow-up data available. This is not necessarily the same as an analysis of all randomized participants. The registry record does not report the number randomized to each arm, reasons for non-completion, or how missing primary endpoint data were handled. It also does not report whether participants were analyzed according to assigned arm or treatment received.

Missing data can affect an endpoint when participants without recorded outcomes differ from those with observed outcomes. In general, excluding participants with unavailable outcomes can change the composition of the analyzed groups. The available record does not establish whether the missingness was related to treatment, outcome, or other factors. The primary counts should consequently be interpreted as applying to the stated completed-study, follow-up-available population, rather than assumed to represent all enrolled or randomized participants.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: grade 3 colitis (16.7%), grade 3 sinus tachycardia (8.3%).

The separate adverse-event listing reports 3 FMT participants among 12 at risk with serious adverse events, and 0 placebo participants among 5 at risk. It reports 6 FMT participants among 12 at risk with other adverse events, and 1 placebo participant among 5 at risk. No deaths are reported in either arm.

The serious-event terms listed most prominently are Grade 3 Colitis at 16.7% and Grade 3 Sinus Tachycardia at 8.3%. These are reported percentages; the registry record details do not identify the denominator for these term-specific percentages or provide enough detail to infer how many participants experienced each term. The percentages should not be converted into counts without that information.

These safety summaries are distinct from the primary endpoint, which counts participants with FMT-related adverse events of Grade 2 or above in the smaller completion-and-follow-up population. Seriousness and severity grade describe different aspects of an adverse event, and the separate listing does not establish that all serious events were considered FMT-related. Details of relatedness assessment and event overlap are not reported in the registry record. The summaries describe recorded events; they do not by themselves establish causation or provide a complete comparative safety estimate.

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

The primary result establishes that 4 participants in the assessed FMT group had an FMT-related adverse event of Grade 2 or above, while 0 assessed participants in the placebo group had such an event. It is a descriptive finding within the endpoint population and assessment period stated in the registry record.

It does not establish how precisely the underlying event experience differs between study arms. No confidence interval or inferential comparison is reported, and the record states that a binary two-arm comparison was not estimable. The small endpoint groups further mean that the observed counts may be sensitive to outcomes in individual participants. The result is not equivalent to a definitive estimate for all enrolled participants, because the endpoint population is restricted to those who completed the study and had follow-up data.

The result also does not answer whether FMT changes remission, inflammatory biomarkers, donor microbiome presence, or disease activity. Those are listed secondary outcomes, but their numeric results are not reported in the registry record. A safety count cannot stand in for an efficacy result, and the registry’s stated primary aims were safety and tolerability.

Nor does the primary endpoint count establish that every event was caused by FMT. The outcome is labeled FMT-related, but the process used to assess relatedness is not reported in the registry record. The separate serious-event listing is not interchangeable with the primary endpoint and should not be interpreted as if it were a count of all events meeting that endpoint’s definition.

In general, a randomized, masked comparison can help reduce certain biases, but it cannot eliminate uncertainty arising from limited participant numbers, unavailable follow-up, or incomplete reporting. The appropriate conclusion is limited to the observed counts and the record’s stated populations. The result does not establish a broad safety profile, a causal effect, or a clinical benefit or lack of benefit.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates why an outcome count must be read alongside its definition, denominator, and analysis population. The primary endpoint is not simply “adverse events”: it is the count of participants with FMT-related events of Grade 2 or above, among participants who received study treatment, completed the study, and had follow-up data. The separate adverse-event summaries use different at-risk denominators and address different safety categories.

The record also shows the limits of descriptive results when groups are small. Counts can be communicated plainly, but without an estimable comparison or uncertainty interval they do not show how precisely the arms differ. A zero observed count in one group is still a description of that group, not proof that the event cannot occur. Conversely, the observed events in the FMT group do not, by themselves, establish causation.

Another statistical issue is the distinction between planned objectives and analyzed results. Several secondary outcomes are listed, but numeric results are not reported in the registry record among the registry entries, and the record reports no analyses. The outcome list therefore cannot be treated as a set of findings. Transparency about analysis populations, missing data, multiplicity, and estimation methods would be needed to interpret a fuller set of results.

Finally, sample-size planning illustrations based on an observed effect are not the same as a prospective design justification or an observed-power calculation. They depend on stated assumptions and should be understood as planning exercises. The original sample-size justification and detailed statistical plan are not reported in the registry record.

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 endpoint data come from 8 participants in the FMT arm and 5 in the placebo arm, although overall enrollment is reported as 15. The registry record does not explain why the primary endpoint population is smaller than total enrollment or provide the number randomized to each arm. Because the endpoint requires study completion and available follow-up, the result may not describe all enrolled participants.

The safety listing uses 12 FMT participants and 5 placebo participants at risk for adverse events, unlike the primary endpoint population. The record does not explain the FMT denominator difference, the extent of overlap between events, or how the reported serious-event terms relate to the primary endpoint. Term-specific denominators are not reported in the registry record.

The study combines participants with active ulcerative colitis and active Crohn’s colitis. Outcome counts by diagnosis, age subgroup, or other participant characteristics are not reported in the registry record. The available information therefore does not permit assessment of whether findings varied across these subgroups.

Further limitations include the absence of reported confidence intervals, inferential tests, detailed missing-data methods, a sample-size justification, and a full statistical analysis plan. The registry record does not report the approach to event grading or attribution, or details sufficient to reconstruct the randomization and masking procedures. Secondary outcome values are not reported among the registry entries. These reporting gaps constrain interpretation and prevent a broader estimate of safety or other outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fecal Microbiota Transplant (FMT) in Pediatric Active Ulcerative Colitis and Pediatric Active Crohn's Colitis — NCT02330653.
• Registry record last updated 2023-10-16; status last verified 2023-10.
• Results first posted 2023-10-16.
• 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 NCT02330653, a completed Phase I/II, randomized, quadruple-masked, parallel, placebo-controlled, single-center study of FMT in active pediatric ulcerative colitis and Crohn’s colitis. Enrollment was 15. The recorded start was 2015-11, and primary completion was 2019-04-08.

The primary outcome was the number of participants with FMT-related adverse events of Grade 2 or above. The posted counts were 4 of 8 in the FMT arm and 0 of 5 in the placebo arm among participants who completed the study and had follow-up data. The separate safety listing reports serious and other adverse events using different denominators, with no deaths reported.

The registry lists four secondary outcomes, but numeric secondary results and analyses are not reported in the registry record among the registry entries. A two-arm comparison for the binary primary endpoint was not estimable. The statistical plan, sample-size justification, and handling of missing data are not reported in the registry record.