This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption (NCT03270085), a randomized phase 2 study. The primary outcome is Total Fecal Bile Acid (BA) Excretion.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03270085 |
| Phase | Phase 2 |
| Condition | Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea, Bile Acid Malabsorption |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 30 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns people with diarrhea-predominant irritable bowel syndrome (IBS-D) and bile acid malabsorption (BAM). Chronic diarrhea is also listed among the conditions. The registry record does not give additional eligibility details or describe the characteristics of participants who enrolled, so the findings cannot be placed in a more detailed clinical profile from this record alone.
Intervention
The active treatment was colesevelam. The record describes baseline testing, a treatment period and treatment testing, with nine visits over five to nine weeks. It does not report a dose in the intervention information available in the registry record.
Comparator
The comparison group received placebo. The trial is listed as randomized, with parallel groups and triple masking. The record does not specify which participant, clinician or study staff roles were masked.
Primary question
The primary endpoint was total fecal bile acid excretion, measured in μmoles/g at treatment day 28. The reported median was 10.7 for colesevelam and 3.6 for placebo; the registry reports a Wilcoxon (Mann-Whitney) comparison with p = 0.001. This addresses whether the observed distributions differed between the randomized groups on this measure. It does not, by itself, establish a change from baseline, explain the clinical importance of the difference, or address outcomes beyond those reported.
3. Trial Design
This was a Phase 2, randomized, parallel-group trial of colesevelam versus placebo. Its official title describes it as double blinded, while the registry record classifies masking as triple. These descriptions do not identify which roles were masked, so the masking arrangement cannot be specified further from the record. The trial status is completed. The recorded start date is 2017-12-07 and the primary completion date is 2019-05-31.
The registry lists enrollment as 30. The posted results report 15 participants in each treatment group for the primary outcome. The study description says the comparison was intended to examine colonic transit, bowel functions, permeability and tight junction expression in rectosigmoid mucosa, in addition to the primary bile acid outcome. The record lists Number of Stools Per Day as a secondary outcome and states that there were three outcome measures and three analyses. The details of all those measures and analyses are not fully available in the information recorded for this result.
The arm descriptions outline baseline testing, treatment and treatment testing. They describe nine visits over five to nine weeks. For colesevelam, the recorded baseline description mentions a transit test and a high-fat diet with stool collection; the placebo description also refers to baseline and treatment testing. The arm descriptions are incomplete, so they do not support a full reconstruction of the visit schedule or procedures.
Randomization and placebo comparison can help make treatment groups comparable, while masking can limit some forms of expectation or assessment bias. Those features do not eliminate uncertainty, especially in a trial with the reported group sizes. Details such as the randomization procedure, allocation concealment, treatment dose, adherence, participant flow and analysis 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
| Stage | Colesevelam | Placebo |
|---|---|---|
| STARTED | 15 | 15 |
| COMPLETED | 14 | 15 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Colesevelam | Placebo |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
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.
| Characteristic | Unit | Colesevelam | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 15 | 30 | |
| Age, Continuous | years | 44 (34 to 52) | 56 (40 to 68) | 50 (34 to 67) |
| Sex: Female, Male: Female | Participants | 11 | 13 | 24 |
| Sex: Female, Male: Male | Participants | 4 | 2 | 6 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 13 | 15 | 28 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Region of Enrollment: United States | participants | 15 | 15 | 30 |
| Body Mass Index | kg/m2 | 33.2 (28.0 to 37.6) | 33.6 (28.2 to 36.4) | 33.4 (28.0 to 36.7) |
6. Primary Endpoint
The registry lists the primary outcome as Total Fecal Bile Acid (BA) Excretion, measured over Treatment day 28.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | μmoles/g |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is total fecal bile acid (BA) excretion, expressed in μmoles/g of stool. The registry says it was measured using high-performance liquid chromatography/tandem mass spectrometry after methanol extraction of single stool samples. The record describes samples at baseline and at the end of treatment, and gives the primary outcome timeframe as treatment day 28.
Fecal bile acid excretion is a laboratory measure of bile acids in stool. In this trial, it provides a biological outcome that can be compared between the colesevelam and placebo groups. The measure is distinct from patient-reported bowel symptoms and from the listed secondary outcome, Number of Stools Per Day. Measuring a biological endpoint can address whether groups differ on that specific laboratory measure, but it does not automatically show that participants felt better or that any difference matters to patients.
The posted group results are medians, with the registry identifying the accompanying spread as an interquartile range. The record reports values at the treatment endpoint, but it does not provide baseline group values or a baseline-adjusted treatment estimate for this outcome. Accordingly, the endpoint results should be read as a comparison of the posted treatment-day measure, not as a quantified change from baseline. The record also does not report a clinical threshold for interpreting a difference in μmoles/g.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For total fecal bile acid excretion at treatment day 28, the registry reports a median of 10.7 μmoles/g in the colesevelam group and 3.6 μmoles/g in the placebo group. The reported interquartile ranges are 8.2 to 17.4 and 2.6 to 7.2, respectively. The registry reports a Wilcoxon (Mann-Whitney) comparison with p = 0.001. These values describe a higher observed distribution of fecal bile acid excretion in the colesevelam group in this trial.
The p-value is evidence against the null hypothesis used for the reported group comparison, under the test's assumptions. It is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of the group difference. A p-value also does not convey how precisely the treatment effect is estimated. The registry record does not report a confidence interval or a numerical between-group effect estimate for this analysis.
The reported medians and interquartile ranges are useful descriptions of the group results. Medians locate the middle of the ordered observations, while interquartile ranges describe the central spread of those observations. They do not show every participant's value or identify how much the individual observations overlap. As a result, these summaries do not show the full distributions or the range of individual responses.
The result is limited to the primary laboratory endpoint and the people enrolled in this trial. It should not be translated into a claim about symptom improvement, bowel function, colonic transit or mucosal measures unless those outcomes are separately reported and evaluated. The registry includes Number of Stools Per Day as a secondary outcome, but does not give its result in the available record. It also notes missing or non-estimable values for another endpoint in a two-arm comparison.
The record does not state whether the primary analysis adjusted for baseline values, how missing observations were handled, or which analysis population was used. It does not provide a confidence interval, a prespecified clinical threshold, or a detailed statistical analysis plan. These omissions limit assessment of precision and of how the analysis was specified before results were known. The reported p-value supports a between-group statistical difference on the primary endpoint under the sponsor's stated test; it does not establish the broader clinical meaning of that result.
9. Statistical Methods Explained
What comparison was reported? The registry identifies the primary analysis as a Wilcoxon (Mann-Whitney) test comparing colesevelam with placebo. This is a rank-based method for comparing two groups. Rather than relying on a comparison of means under a normal-distribution model, the method uses the ordering of observations across the groups. It can be useful when a continuous outcome is skewed or when a mean-based summary is not the intended description. The registry reports medians and interquartile ranges for this endpoint, which are consistent with a distribution-focused presentation.
What does a rank-based test tell the reader? In general, a Mann-Whitney test assesses whether observations in one group tend to be higher or lower in rank than observations in the other group. Its result should not automatically be described as a test of medians alone. A median-only interpretation requires assumptions about the shapes of the group distributions. The posted medians give a simple account of the middle values, while the interquartile ranges describe central spread; neither replaces the test's use of the ordered observations.
The reported p-value is 0.001. In general, a p-value is calculated under a null model and indicates how incompatible the observed test statistic, or a more extreme one, is with that model. It does not state the probability that the treatment has no effect, and it does not measure the probability that the finding is due to chance in a simple, direct sense. It also does not tell the reader the magnitude or clinical relevance of the difference. Interpretation depends on the test, the analysis plan and the broader evidence, some of which are not reported in the registry record.
What does the spread report? The endpoint is summarized by medians and interquartile ranges. In general, the interquartile range spans the middle half of observed values. It describes variability without requiring the outcome to be summarized by its mean and standard deviation. The reported intervals are 8.2 to 17.4 for colesevelam and 2.6 to 7.2 for placebo. They are not confidence intervals for the group medians or for a treatment contrast. A confidence interval for an effect estimate would instead describe uncertainty around that estimate under the statistical method used. No such interval for the between-group comparison is reported in the registry record.
Why can the exact estimate matter? A test result can indicate evidence of a difference without showing its estimated size precisely. An effect estimate and confidence interval can help readers judge both magnitude and uncertainty. Here the record provides the group medians and their interquartile ranges, but it does not give a numerical contrast between groups or a confidence interval for that contrast. No new contrast should be inferred from the separate group summaries. The record also does not state whether the analysis used baseline adjustment or another covariate adjustment.
What is over-dispersion, in general? Over-dispersion occurs when outcome variability is greater than a statistical model expects. In general, a model that ignores excess variability can produce uncertainty estimates that are too narrow and tests that are too optimistic. This concept is relevant to some count-data models, but the primary endpoint is reported as a continuous laboratory measure analyzed with a rank-based test. The registry does not report an over-dispersion model for this endpoint, and the posted information does not establish that over-dispersion was assessed. The concept should not be taken as a description of an observed problem in this trial.
What can the sample-size illustrations mean? In general, an illustrative sample-size calculation describes how many participants per arm might be required under stated assumptions to detect a chosen effect with a chosen power and significance level. Such an illustration is conditional on those assumptions and is not an estimate of the probability that the completed trial detected an effect. The record's stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation and fractions of the observed effect. The listed sample sizes are planning illustrations, not observed power and not a replacement for the trial's design justification. The trial's own sample-size justification is not reported in the registry record.
What remains unclear about the analysis? The registry reports three analyses, but detailed specifications for the primary analysis are limited. It does not report whether the Wilcoxon test was one-sided or two-sided, whether any exact or asymptotic calculation was used, how ties were handled, or whether there were prespecified adjustments for multiple outcomes. The record also does not specify the handling of missing endpoint measurements or the analysis population. These omissions do not invalidate the posted result, but they restrict independent appraisal of its assumptions and reproducibility.
General statistical interpretation should distinguish what is directly reported from what is not. The directly reported primary result is a group comparison of treatment-day fecal bile acid excretion, described by medians and interquartile ranges and tested with a Wilcoxon (Mann-Whitney) method. The size and precision of a treatment contrast, the baseline-adjusted result and the analysis details beyond that description are not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wilcoxon (Mann-Whitney) | not reported | 0.001 |
The registry's reported analysis is a Wilcoxon (Mann-Whitney) comparison, with p = 0.001. It is accompanied by group medians and interquartile ranges for colesevelam and placebo. The registry record does not provide a separate recalculated treatment estimate or a recalculated p-value for this comparison, so a numerical comparison between the sponsor's analysis and a recalculation cannot be made from the record.
The discrepancy flag is false, but that does not supply missing numerical details or create an independent estimate. The sponsor's reported test should therefore be read as the available inferential analysis, while recognizing that the record does not state all the details needed to reproduce it. No separate confidence interval for the group contrast is reported. The group summaries alone cannot be used to reconstruct that interval or a test result reliably. The sponsor's analysis addresses the stated primary endpoint comparison; it does not resolve questions about clinical importance, missing data, adjustment for baseline, or the treatment effect on outcomes that are not reported.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and three analyses, and identifies Number of Stools Per Day as a secondary outcome. The available result information gives the primary outcome result but does not include the secondary outcome result. It also records that values were missing or not estimable for a two-arm comparison for another endpoint. The particular endpoint and the reason values were unavailable are not specified in the record.
When a study evaluates multiple outcomes or performs multiple analyses, the chance of obtaining at least one small p-value can increase if each test is interpreted without accounting for the family of tests. In general, a prespecified multiplicity strategy can define which outcomes are confirmatory and how the interpretation of tests is adjusted. Whether such a strategy was planned or used is not reported in the registry record. The reported p-value should therefore be understood as the result of the stated primary analysis, not as evidence that all outcomes were positive or that multiplicity was addressed.
The record does not report the number of participants with available primary endpoint data, the amount or pattern of missing data, or the method used to handle missing measurements. It also does not identify whether the primary analysis included all randomized participants, only participants with observed measurements, or another analysis population. These details matter because exclusions or missing observations can affect how well the analysis preserves the benefits of randomization and how representative the analyzed group is of those randomized.
The record does not give a detailed statistical analysis plan, a protocol for handling missingness, or an account of interim analyses. Those procedures should not be inferred from the trial's completed status or the posted result. The information available supports description of the reported primary comparison, but not a full assessment of multiplicity control, missing-data assumptions or analysis-population choices.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Colesevelam | 0 | 15 | 0.0% |
| Placebo | 0 | 15 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Colesevelam | 0 of 15 |
| Placebo | 0 of 15 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Colesevelam | 0 of 15 |
| Placebo | 0 of 15 |
For the adverse-event information recorded, the colesevelam group had zero serious adverse events among 15 at risk, zero other adverse events among 15 at risk, and zero deaths. The placebo group had zero serious adverse events among 15 at risk, zero other adverse events among 15 at risk, and zero deaths. No serious adverse-event terms are listed.
These figures describe the events recorded in the registry for the trial. Zero reported events is not proof that an event cannot occur, and it does not establish that the treatments have identical safety profiles. In general, small trials have limited ability to characterize uncommon harms, and a short study may not capture effects that arise later. The registry record does not provide detailed definitions, collection procedures, follow-up beyond the described study period, or a narrative account of adverse events. The figures should therefore be read as a report of no recorded events in the listed categories during the reported study, not as a comprehensive safety assessment or as medical advice.
13. What the Result Does, and Does Not, Mean
The primary result shows that the posted median total fecal bile acid excretion at treatment day 28 was higher in the colesevelam group than in the placebo group. The registry reports a Wilcoxon (Mann-Whitney) p-value of 0.001 for the group comparison. This is evidence of a statistical difference on the laboratory endpoint under the reported analysis. It is a finding about this measure in this trial, not a direct measure of symptom relief or overall clinical benefit.
The result does not establish whether participants had fewer stools, improved bowel function, or changes in colonic transit or mucosal permeability. Although the trial description names several areas of interest and the record lists Number of Stools Per Day as a secondary outcome, those results are not reported in the available information. Nor does the primary endpoint comparison quantify a change from baseline: baseline sampling is described, but baseline values and a change estimate are not reported.
The record also does not give a confidence interval for the treatment contrast or a threshold for deciding whether a difference in fecal bile acid excretion is clinically meaningful. The medians and interquartile ranges describe the observed groups, but do not show the full distribution of responses or precisely estimate the treatment contrast. The absence of a reported result for another endpoint and the limited information about missing data further constrain interpretation.
Accordingly, the result can support a narrow statement about the observed primary laboratory endpoint and its reported statistical test. It cannot, by itself, establish a broader effect on IBS-D symptoms, demonstrate long-term outcomes, or settle the balance of benefits and harms. Those questions require outcomes and follow-up that are not reported in the registry record.
14. Why This Trial Matters Statistically
This trial illustrates why the endpoint and the statistical test need to be read together. The primary measure is a laboratory result expressed in μmoles/g, summarized with medians and interquartile ranges and compared using a rank-based test. That combination presents information about the middle and spread of the observed values while avoiding an assumption that the primary comparison is a conventional difference in means. It also requires care: a rank-based p-value is not itself a treatment-effect estimate or a measure of clinical importance.
The trial also illustrates the distinction between evidence of a statistical difference and precision about its size. The registry reports p = 0.001, but no confidence interval or numerical between-group effect estimate. Readers can see the group summaries, but cannot assess a reported interval around the treatment contrast or compare it against a clinical threshold defined in the record. Precision is not conveyed by a small p-value alone.
Finally, the result sits within a broader study description that includes bowel function and biological measures, while the available registry results are incomplete for some endpoints. This highlights the value of transparent reporting of outcome definitions, analysis populations, missing-data methods, multiplicity decisions and estimates with uncertainty. The record offers a focused statistical result, but important details for judging its scope and reproducibility are not reported.
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 registry record gives limited information about participant characteristics and eligibility criteria. It identifies IBS-D and bile acid malabsorption in the trial title and lists related conditions, but does not describe the enrolled group in detail. Applicability to people with different clinical characteristics cannot be judged from the available information.
The primary outcome is reported at treatment day 28, with group medians and interquartile ranges. The registry describes baseline and end-of-treatment stool samples, but does not post baseline group values or a baseline-adjusted estimate. It also does not report a confidence interval for the group contrast or a clinical threshold for interpreting its magnitude. This limits assessment of the size, precision and clinical relevance of the finding.
Details of the treatment regimen are not fully available. The arm descriptions outline a study period with nine visits over five to nine weeks, but do not provide a dose in the recorded intervention information. The descriptions are incomplete, and the masking classification and official-title wording differ without specifying which roles were masked. These gaps limit reconstruction of the conduct of the trial from the registry record.
The registry does not report the analysis population, adherence, participant flow, the number of missing primary measurements, or the method used to handle missing data. It also does not describe a detailed statistical analysis plan or a multiplicity strategy. The result for the listed secondary outcome is not available, and another endpoint is noted as missing or not estimable for a two-arm comparison. Together, these omissions constrain evaluation of robustness and of how the primary result fits among the study's other outcomes.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption — NCT03270085.
- Registry record last updated 2020-04-27; status last verified 2020-03.
- Results first posted 2020-04-27.
- 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.
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19. Record Summary
NCT03270085 is a completed Phase 2 randomized, parallel-group trial comparing colesevelam with placebo in people with IBS-D and bile acid malabsorption. The primary endpoint was total fecal bile acid excretion at treatment day 28, measured in μmoles/g. The posted medians were 10.7 for colesevelam and 3.6 for placebo, with interquartile ranges of 8.2 to 17.4 and 2.6 to 7.2. The registry reports a Wilcoxon (Mann-Whitney) p-value of 0.001.
The result indicates a statistical difference on the reported laboratory endpoint. The record does not provide a confidence interval or numerical treatment contrast, and does not report the result for the listed secondary outcome. Details on missing data, analysis populations and multiplicity are also not reported in the registry record. The primary finding should therefore be interpreted within the limits of the posted endpoint and analysis information.