C. Difficile and Ursodiol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for C. Difficile and Ursodiol (NCT02748616), a na phase 4 study. The primary outcome is Percent of Patients With Return Toward a Normal Fecal Bile Acid Pattern.

2. Clinical Question

3. Trial Design

The registry identifies NCT02748616 as a completed Phase 4, single-group clinical trial sponsored by NYU Langone Health. The listed start date is 2017-03-01, and the primary completion date is 2019-11-01. Enrollment is recorded as 9 participants. The record does not describe a randomized allocation process: allocation is listed as NA, the model is single group, and masking is none.

The intervention is ursodiol. The arm description states that participants began 300 mg following Visit #1 and continued for 8 weeks. The brief summary describes ursodeoxycholic acid treatment for two months, beginning with Metronidazole and/or Vancomycin, which it describes as antibiotics used for acute C. difficile infection for 8 to 10 days. These statements describe the planned treatment context; they do not establish how many participants completed treatment or followed the regimen.

The primary outcome is the percentage of patients with return toward a normal fecal bile acid pattern, measured at 2 months. The trial record lists one outcome measure and no analyses. It does not report a comparison group, the actual primary outcome result, or the methods used to analyze participant data. The record also does not describe how patients were selected, the specific eligibility criteria, or the timing and content of study visits beyond the arm description's reference to Visit #1. Those details are not reported in the registry record.

Because the design has one group and no concurrent comparator, changes in the measured pattern cannot be separated from other influences using a randomized treatment contrast. The registry's completion status is a study-status entry; it does not itself indicate that results were reported or establish what the outcome showed.

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

Reasons for not completing this period:

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 Percent of Patients With Return Toward a Normal Fecal Bile Acid Pattern, measured over 2 months.

The primary endpoint is the percentage of patients with return toward a normal fecal bile acid pattern at 2 months. It is a binary-style outcome summarized as a percentage: each participant would be classified according to whether the specified pattern was observed, and the group result would express the proportion meeting that description. A percentage can make the frequency of an outcome easier to interpret than an uncontextualized count, but its meaning depends on the definition of the pattern and on who was included in the calculation.

The registry record does not give an operational definition of “return toward a normal” pattern, a threshold for classifying an individual, or the number of participants assessed at 2 months. It also does not report the observed percentage. Consequently, the endpoint's label identifies the intended measurement but does not permit a reader to determine the result or its precision.

The brief summary explains the biological rationale in terms of bile acids and C. difficile growth. That rationale is not the same as a measured clinical outcome. The listed endpoint concerns a fecal bile acid pattern, rather than directly reporting recurrence, diarrhea, or another patient-level clinical event. The registry record does not state how the primary endpoint relates to those clinical outcomes or whether they were assessed as additional outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and outcome type determine what statistical claims can be made. This study is recorded as a single-group trial with a percentage endpoint. The registry lists no analysis results, so the discussion below explains general statistical concepts and the stated planning assumptions; it does not describe an analysis result from this trial.

What does a percentage endpoint represent?

For a binary outcome, each person is classified into one of two categories according to an outcome definition. A group percentage then describes the share classified as having the event or meeting the endpoint. Such a summary is only interpretable when the endpoint definition, number meeting it, and denominator are known. In this record, the endpoint is “return toward a normal fecal bile acid pattern,” but the classification rule and observed percentage are not reported in the registry record. That makes it impossible to assess the result or verify which participants contributed.

Percentages are estimates based on the participants observed. Statistical uncertainty concerns how much the estimate could vary across comparable samples. A confidence interval is a range produced by a statistical method to express that uncertainty under its assumptions. A narrow interval generally indicates greater precision than a wide interval, while an interval alone does not resolve limitations in study design or measurement. No confidence interval for the primary endpoint is reported in the registry record.

Why does the single-group design matter?

A randomized comparison estimates a contrast between groups formed to be comparable by the randomization process. A single-group study has no concurrent randomized group to provide that contrast. General changes over time, other treatments, or differences in participant circumstances can therefore be difficult to distinguish from changes associated with the study intervention. The record identifies no randomized comparison and does not report an adjustment strategy that would address confounding. This is a design limitation, not a result of a statistical test.

Repeated measurements can sometimes describe within-person change, but the registry record does not report a baseline endpoint value, follow-up values, or a paired analysis. Even when within-person data are available, a pre-post change is not equivalent to a randomized treatment effect. The information needed to determine whether such an analysis was performed is not reported in the registry record.

How should the planning assumptions be understood?

The stated sample-size calculations are planning illustrations based on an observed effect, not the trial's own design justification. Their assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a portion of the observed effect. Those are hypothetical comparison assumptions, whereas this registry record describes a single-group study and no randomized comparator. The calculations should therefore not be mistaken for the actual allocation or analysis plan for this trial.

A sample-size illustration asks how much information a hypothetical design might require under specified assumptions. It does not show that a study had adequate power for its actual design, and it is not observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty. The registry record does not report the trial's own sample-size justification or statistical plan, so those details cannot be inferred from the planning assumptions.

What can be said about statistical significance?

A significance test evaluates data against a specified null hypothesis under a statistical model. Its p-value is not a measure of the probability that a treatment works, nor does a threshold by itself describe the size or clinical importance of an effect. Interpretation would require a reported test, a clear endpoint definition, and enough information about the analyzed participants and model. No p-value or inferential analysis for the primary endpoint is reported in the registry record.

For a percentage outcome, analysis may depend on the number of events and the denominator. With a small observed group, the estimate can be sensitive to the outcome of individual participants and uncertainty can be substantial. This is a general statistical consideration; the registry record does not report the endpoint counts needed to characterize uncertainty in this study.

Why are analysis populations and missing observations important?

The population used in an analysis determines what the result represents. An analysis of everyone enrolled differs from one restricted to participants who completed treatment or had a measured endpoint. Missing outcome data can also affect the estimate if the availability of measurements is related to participant status or outcome. The registry record does not identify the primary analysis population, report missing primary outcome data, or state a missing-data method. Consequently, the endpoint denominator and the handling of incomplete follow-up are 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("Ursodiol")
n      <- c(2)
events <- c(2)
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  Ursodiol  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study tests multiple outcomes, time points, groups, or statistical hypotheses. Repeated testing can increase the chance of a nominally notable finding even when no true effect exists. Statistical plans commonly specify which outcome is primary and how additional tests will be handled. The registry lists one outcome measure, but does not report a multiplicity strategy or a detailed statistical analysis plan. It is therefore not possible to determine whether other outcomes or analyses were planned, or how any multiple testing would have been addressed.

The record does not report the primary outcome result or an analysis. It also does not state which participants were included in the primary analysis, how many had a measurement at 2 months, whether any observations were missing, or how missing values were handled. These are important details because an outcome percentage depends on the denominator and on the rules used to include participants. They are not reported in the registry record.

The record lists enrollment of 9, but does not say that all enrolled participants were analyzed. Nor does it identify an intention-to-treat population, a per-protocol population, or another analysis set. Those labels should not be inferred from the study design or enrollment figure.

The registry lists no analyses. It does not report interim analyses, stopping rules, or procedures for adjusting inference following interim looks. These details are not reported in the registry record. Their absence from the record does not establish whether such procedures existed; it means they cannot be evaluated from the available information.

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.

The registry records safety figures for the Ursodiol group with 2 participants at risk for serious adverse events and 0 affected. For other adverse events, it likewise records 2 at risk and 0 affected. Deaths are recorded as 0. No serious adverse-event terms are listed.

These entries describe the counts in the registry record; they should not be extended beyond the stated at-risk group. The study enrollment is 9, but the safety entries list only 2 at risk. The record does not explain why the safety denominator differs from enrollment or whether the same participants were at risk for each category. The listed counts do not establish the completeness of safety follow-up for everyone enrolled.

A count of zero affected is not evidence that an event is impossible or that risk is absent. Safety interpretation depends on how many people were monitored, the duration and completeness of follow-up, and how events were defined and collected. Those details are not reported in the registry record. The entries also do not provide a comparison with another group, so they cannot quantify a relative difference in adverse events.

These figures are descriptive registry entries, not a full safety analysis. They should be read alongside the limited denominator and missing details, rather than as evidence about safety for a broader population.

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

The record establishes that a completed, single-group Phase 4 study of ursodiol was registered, with enrollment of 9 participants and a primary endpoint focused on return toward a normal fecal bile acid pattern at 2 months. It describes an intended regimen of 300 mg ursodiol for 8 weeks and gives a rationale related to bile acids and C. difficile. These are design and background details, not a report of the endpoint's observed result.

The primary percentage, its denominator, and an uncertainty estimate are not reported in the registry record. Accordingly, the record does not show how many participants met the endpoint or how precisely any group percentage was estimated. It also does not report whether participants experienced recurrent C. difficile infection as a clinical outcome. A proposed biological explanation cannot fill in these missing results.

Because the study is single group and has no concurrent control, its design cannot provide a randomized comparison of ursodiol with an alternative. Any change observed within a single group could have several explanations. The design alone cannot isolate the contribution of ursodiol from other influences, including the treatment context described in the brief summary.

The safety entries record 0 serious adverse events, 0 other adverse events, and 0 deaths among the stated at-risk counts of 2. They do not account for the full enrollment figure, and the record does not explain the difference. These limited counts should not be read as a comprehensive safety assessment.

In general, a result is most informative when the endpoint is clearly defined, the analysis population and denominator are stated, and the estimate is accompanied by a measure of uncertainty. Those details are not reported for the primary endpoint. The registry record therefore permits a description of the study's intent and design, but not an estimate of treatment effect or a conclusion about clinical benefit or harm.

14. Why This Trial Matters Statistically

This trial illustrates why a registered study design and a reported result are different kinds of information. The record gives an intended intervention, a single-group design, and a named primary endpoint, but does not report the endpoint value or its analysis. Without the result, the central quantitative question cannot be answered from the registry record.

It also illustrates why the endpoint definition and denominator matter. A percentage is not self-interpreting: readers need to know what qualified as a “return toward a normal” pattern, how many participants were assessed, and how missing measurements were handled. Those details are not reported in the registry record. Enrollment alone does not establish the number contributing endpoint data.

The design distinction is equally important. A single-group study can document observations in its participants, but it does not create the randomized contrast needed to separate a treatment effect from other changes over time. This remains true even when there is a plausible biological rationale. Statistical reasoning must distinguish mechanistic motivation, within-group observation, and comparative evidence.

Finally, planning illustrations and safety counts need context. Hypothetical sample-size assumptions do not establish the original trial's design justification or actual statistical power. Safety counts for 2 participants cannot automatically be interpreted as covering all 9 enrolled participants. Together, these features show why transparent reporting of methods, analysis populations, outcomes, and denominators is essential for readers to judge what a small clinical study can establish.

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 outcome is not reported as a result. The registry provides a measure and timeframe, but not the observed percentage, event count, denominator, or uncertainty interval. It also does not define the rule for deciding that a participant had a return toward a normal fecal bile acid pattern. This prevents independent assessment of the endpoint and its precision.

The recorded enrollment is 9, but the number assessed at the 2-month endpoint is not reported in the registry record. Completion of follow-up, treatment adherence, withdrawals, exclusions, and missing measurements are also not described. Thus, enrollment should not be treated as the number analyzed.

The study is single group, with allocation listed as NA and no masking. No concurrent control is described, so the design does not support a randomized treatment comparison. The record does not report statistical methods that could address confounding or distinguish treatment-associated changes from other changes over time.

The brief summary describes a rationale involving bile acids and concurrent antibiotic treatment, but the record does not report clinical recurrence results or show whether the proposed biological pathway was measured as a mediator. It also does not provide an operational endpoint definition or explain how the endpoint relates to clinical outcomes.

Safety entries list 2 participants at risk, while enrollment is 9; the reason for this difference is not stated. The record does not describe the safety observation period or event-collection procedures. Finally, the statistical analysis plan, the trial's own sample-size justification, and handling of multiplicity are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: C. Difficile and Ursodiol — NCT02748616.
• Registry record last updated 2022-01-11; status last verified 2021-12.
• Results first posted 2021-02-17.
• 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

NCT02748616, “C. Difficile and Ursodiol,” is recorded as a completed Phase 4, single-group study sponsored by NYU Langone Health. Enrollment is 9, and the registry lists diarrhea as a condition. The record gives a study start date of 2017-03-01 and a primary completion date of 2019-11-01.

The intervention is ursodiol. The arm description states 300 mg for 8 weeks, beginning after Visit #1. The primary endpoint is the percentage of patients with return toward a normal fecal bile acid pattern at 2 months. The registry record does not report the primary endpoint result, an analysis, or the endpoint denominator. Allocation is listed as NA, masking as none, and no concurrent control group is described.

Safety entries list 2 participants at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. The record does not explain the safety denominator. It also does not report the statistical analysis plan, missing-data approach, or analysis populations.