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 Ability of Mayo Clinic High-performance Liquid Chromatography (HPLC) Method to Measure Fecal Bile Acids (NCT02111603), a na phase 4 study. The primary outcome is Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02111603 |
| Phase | Phase 4 |
| Condition | Diarrhea Predominant Irritable Bowel Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
The study asks whether the Mayo Clinic HPLC method can detect a change in fecal bile acid excretion after colesevelam treatment in patients with diarrhea-predominant irritable bowel syndrome. The stated hypothesis is that colesevelam reduces fecal bile acid excretion in patients with prior evidence of increased 48-hour total fecal bile acid excretion. The emphasis is on assay responsiveness: whether measurements made with the method reflect a change over the treatment period.
This is not a question about whether colesevelam performs better than a placebo or another treatment. The registry describes a single-group study, with measurements before treatment and after treatment in participants receiving colesevelam. Without a concurrent control group, a change between those measurements cannot by itself separate a treatment-associated change from other explanations, such as natural fluctuation or changes over time.
Population
Patients with diarrhea-predominant irritable bowel syndrome and prior evidence of increased 48-hour total fecal bile acid excretion. The registry reports that 13 subjects were accrued; 12 participants with complete baseline and post-treatment data are included in the primary outcome.
Intervention
Colesevelam, 1875 mg orally twice daily for 10 days.
Comparator
There is no separate control group. The primary outcome compares measurements at baseline with measurements after treatment in the same participants.
Primary question
Does the HPLC method measure a change in total 48-hour fecal bile acids from baseline after colesevelam treatment?
The registry record does not report the numerical estimate of change. It therefore cannot establish from the posted results how large the measured change was or how precisely it was estimated.
3. Trial Design
The registry identifies NCT02111603 as a Phase 4, completed, single-group study sponsored by Mayo Clinic. Its title focuses on the ability of a Mayo Clinic high-performance liquid chromatography method to measure fecal bile acids, and the official title specifies demonstrating response to colesevelam in patients with diarrhea-predominant irritable bowel syndrome. The registry lists the study start as 2014-04 and primary completion as 2014-08.
Allocation is listed as not applicable, masking as none, and the model as single group. These entries are consistent with a before-and-after design rather than a randomized comparison. Participants received colesevelam at 1875 mg orally twice daily for 10 days. The primary measure used stool collections over 48 hours at baseline, before treatment, and during days 9-10 of dosing. Total fecal bile acids were measured using HPLC/tandem mass spectrometry.
The registry reports that 13 subjects were accrued. One subject withdrew after the pre-drug activities but before treatment activities. The primary outcome includes the 12 participants who had complete data at both baseline and after 10 days of treatment. Thus, the primary outcome population is defined by availability of measurements at both time points, not simply by accrual to the study.
The registry lists one primary outcome and five secondary outcomes: change in fasting serum C4, change in fecal fat excretion, change in stool consistency, change in stool frequency, and concordance correlation coefficients for the relative composition of stool total and the main individual bile acids. It also reports six outcome measures and one analysis. Details of the statistical methods used for that analysis, including how the within-participant measurements were compared, are not reported in the registry record.
Because there is no randomized control group, the design can describe measured change over time in the participants with complete data, but cannot make a like-for-like treatment comparison. The registry does not report a protocol-level sample-size justification or a detailed analysis plan.
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: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities.
Overall Study
| Stage | Colesevelam |
|---|---|
| STARTED | 13 |
| COMPLETED | 12 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Colesevelam |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.
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: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities.
| Characteristic | Unit | Colesevelam |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 43.1 (SD 3.7) |
| Sex: Female, Male: Female | Participants | 11 |
| Sex: Female, Male: Male | Participants | 1 |
| Region of Enrollment: United States | participants | 12 |
| Mean Body Mass Index (BMI) | kg/m^2 | 31.1 (SD 2.4) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam, measured over baseline, 10 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | uM |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in total 48-hour fecal bile acids from baseline in response to colesevelam. It is a continuous measure reported in micromolar units (uM), with the outcome specified as a mean and dispersion specified as standard error. Stool was collected over 48 hours before treatment and during days 9-10 of the 10 days of dosing. Total fecal bile acids were measured using HPLC/tandem mass spectrometry.
The endpoint directly addresses the study's stated measurement question: whether the HPLC method can register a change in fecal bile acids across the treatment period. A biochemical measurement is useful for assessing assay responsiveness because it places the focus on a laboratory-measured quantity rather than a symptom alone. The registry also lists outcomes related to stool consistency and frequency, fecal fat, fasting serum C4, and bile acid composition, but these do not replace the stated primary endpoint.
For a continuous outcome, a mean describes the central value in the analysis population. A standard error describes uncertainty in an estimated mean, rather than the spread of individual observations. The registry record does not report the actual mean change, its standard error, or a confidence interval. As a result, the direction, magnitude, and precision of the primary endpoint cannot be assessed from the posted results described in the record.
The endpoint is based on complete measurements at both time points for 12 participants. It therefore represents the observed before-and-after change among those with complete data, rather than a result for every subject accrued to the study. The record does not report whether any additional endpoint-specific measurement or data-quality rules were applied.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available registry entries establish the clinical measurement being studied, its timing, and the population used for the primary outcome. They do not include the numerical primary-outcome estimate. In particular, the record does not report the mean change in total 48-hour fecal bile acids, its standard error, a confidence interval, or a p-value. Without those values, neither the direction nor the size of the measured change can be stated, and its statistical precision cannot be evaluated.
The stated purpose is to assess whether the HPLC method can demonstrate a response after colesevelam. In statistical terms, that is a measurement-responsiveness question: does the measure change across the defined treatment period in the participants observed? A positive result on that question would not, on its own, establish that the method is reliable in other settings or that the treatment caused the measured change. The record does not report a separate control group, so natural fluctuation, time effects, and other influences cannot be distinguished from treatment-associated change through a randomized comparison.
The primary outcome uses paired time points in the sense that baseline and post-treatment measurements come from the same participants. That structure can be relevant when estimating change because each participant serves as their own reference. However, the registry record does not describe the analysis procedure, so it should not be assumed that a particular paired test or model was used. Nor does the record report adjustment for other variables.
The complete-data definition is important when interpreting the result. Thirteen subjects were accrued, and one withdrew after pre-drug activities but before treatment activities. The primary outcome includes the 12 participants with complete baseline and post-treatment data. This means the outcome is reported for participants with data at both time points; the record does not state how missing measurements beyond the described withdrawal were handled.
Although the registry gives a mean as the outcome parameter and standard error as the dispersion measure, those labels alone are not enough to judge precision. The actual estimate and its uncertainty are needed. A standard error is not the same as the spread of participant-level values, and a confidence interval would communicate a range of values compatible with the data under the analysis assumptions. No such interval is reported in the registry record.
The study is classified as completed, but completion status does not convey the size or evidential strength of the measured change. The posted results cannot be interpreted as showing that the treatment did or did not change fecal bile acids because the numerical outcome is not reported. They also cannot establish superiority over another treatment, since there is no randomized comparison. The most defensible reading is that the registry describes a planned before-and-after assay-responsiveness assessment, while leaving the primary numerical finding unavailable in the registry record.
9. Statistical Methods Explained
The design is a single-group before-and-after study. Participants had a baseline stool collection and another collection during days 9-10 of colesevelam dosing. This arrangement permits estimation of change over time in the measured participants. It does not provide the concurrent comparison that would come from random assignment to a separate control group. The registry lists allocation as not applicable and masking as none. The statistical plan for analyzing the change is not reported in the registry record.
What does a mean change represent?
For a continuous measurement, a mean summarizes the average value in the analysis population. A change score represents how the measurement differs between the defined time points. In this study, the primary endpoint is total fecal bile acids measured over 48 hours, with the stated comparison running from baseline to after 10 days of treatment. The registry identifies the outcome parameter as a mean, but does not report its numerical value. It is therefore not possible to infer whether the observed mean change was an increase or a decrease, or how large it was.
Because each participant is measured at both time points, the observations are related rather than independent. In general, methods for repeated measurements can account for that relationship. The choice of method depends on the data and analysis plan. The registry record does not identify a test, model, transformation, or covariate adjustment, so none should be attributed to this study based only on its design description.
How should standard error be read?
In general, a standard error describes the uncertainty of an estimated quantity, such as a mean. It is distinct from a standard deviation, which describes variability among individual observations. A smaller standard error indicates a more precisely estimated mean under the assumptions of the analysis, but it does not tell how different individual participants were from one another. The registry specifies standard error as the dispersion measure for the primary outcome, but gives no numerical standard error. The precision of the result is therefore not assessable from the registry record.
A confidence interval is a range constructed by a statistical procedure to express uncertainty around an estimate. Its interpretation depends on the method and assumptions used. The record does not report a confidence interval for the primary change. General explanations of confidence intervals do not supply the missing study estimate or establish which values are compatible with this study's data.
What does a single-group design allow?
In general, a before-and-after design can describe whether a measure changed in the observed group during the study period. Since the same participants contribute measurements at both times, the comparison is within participants. But without a separate control group, a change cannot be uniquely attributed to treatment. Time-related variation, measurement variation, and other influences may also contribute. The study's stated aim is to assess the responsiveness of the HPLC method after colesevelam; the design does not directly compare the method with a different assay or compare colesevelam with another intervention.
The record says that total fecal bile acids were measured using HPLC/tandem mass spectrometry. It does not report assay validation results, repeatability estimates, laboratory blinding, or a comparison against a reference method. Those would address measurement properties distinct from whether the endpoint changed over the treatment period.
How should planning calculations be interpreted?
The sample-size planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers detecting a stated fraction of the observed effect. The planning setup is not the trial design: this study is single group, not a two-arm equal-allocation comparison. Any sample-size values in such a planning exercise are illustrative planning quantities, not observed power and not evidence that the completed study had a particular probability of detecting an effect. The registry record does not report a protocol-level sample-size justification or a prespecified target based on an independently stated effect.
In general, planning calculations depend on the assumed effect, variability, significance level, allocation, and analysis method. Changing an assumed detectable effect changes the resulting planning requirement. If a planning calculation is based on the effect observed in the same study, it is retrospective and should not be mistaken for a prospective design rationale. The registry's description of the calculation does not supply the missing primary outcome estimate in the record.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than a model assumes. When a model underestimates variability, its uncertainty estimates may be too small and its statistical conclusions too confident. This concern is especially relevant to outcomes analyzed with probability models whose variance assumptions may not fit the data. The primary outcome is continuous, and the registry does not report a model, distributional assessment, or over-dispersion analysis. There is therefore no basis to claim that over-dispersion was present or that the investigators addressed it.
Overall, the registry gives enough design information to identify the outcome, timing, and complete-data population, but not enough statistical detail to reconstruct the analysis. The actual estimate, uncertainty measure, analysis procedure, and handling of assumptions are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures: the primary change in total 48-hour fecal bile acids and secondary outcomes concerning fasting serum C4, fecal fat excretion, stool consistency, stool frequency, and bile acid composition. It reports one analysis, but does not describe whether or how statistical testing was conducted across the outcomes. A multiplicity adjustment, prespecified hierarchy, or other approach to controlling the interpretation of multiple outcomes is not reported in the registry record.
In general, evaluating several outcomes can create more opportunities for apparently unusual findings to arise by chance. Adjustment procedures can address some aspects of that issue, but their use and interpretation depend on the analysis plan. The existence of multiple registered outcomes does not show that every outcome was formally tested, nor does it establish that any particular correction was applied. The record does not describe the analysis plan in enough detail to determine this.
The primary endpoint population consists of the 12 participants with complete data at both baseline and after 10 days of treatment. The registry reports that 13 subjects were accrued and that one withdrew after the pre-drug activities but before treatment activities. The record does not describe imputation, sensitivity analyses, or other methods for missing outcome data. It also does not state whether the primary analysis was intended to include all accrued subjects under a particular analysis-population definition.
In general, excluding participants without complete outcome measurements can make the analyzed group differ from the group originally accrued, especially if missingness is related to outcome or treatment experience. That possibility cannot be assessed from the registry information alone. The described withdrawal occurred before treatment activities, but the record does not provide enough information to determine whether any other data were incomplete or whether missingness affected secondary outcomes.
Accordingly, the registry record identifies the complete-data basis for the primary outcome but does not report a missing-data strategy, a multiplicity strategy, or a detailed definition of analysis populations beyond the stated primary-outcome inclusion rule.
11. 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 | 12 | 0.0% |
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 | 2 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Colesevelam |
|---|---|---|
| Constipation | Gastrointestinal disorders | 2 of 12 |
The registry lists safety information for the colesevelam group. Serious adverse events were recorded for 0 participants among the 12 at risk. Other adverse events were recorded for 2 participants among the 12 at risk. The registry lists no serious adverse-event terms. The death count is not reported in the registry record.
These counts describe what was recorded in this study group; they do not provide a comparison against an untreated or alternative-treatment group. The design is single group, and the registry does not report a control arm for safety comparisons. A count of 0 serious adverse events in this group should be read as an observed count in the registry, not as evidence that serious events are impossible or that risk is absent.
The registry's safety categories distinguish serious events from other adverse events. It does not provide event descriptions for the two other recorded adverse events in the information summarized in the record, so their nature, timing, and relation to treatment cannot be characterized. The record also does not state how event relatedness was assessed, whether all events were collected in the same way, or whether participants were followed for safety beyond the described treatment period.
These figures are limited to the recorded study group and should be considered alongside the study's size, duration, and reporting completeness. They do not establish comparative safety or quantify risk beyond the participants and observation described in the registry record.
12. What the Result Does, and Does Not, Mean
The study is designed to examine whether the Mayo Clinic HPLC method can measure a change in total fecal bile acids after a defined course of colesevelam in patients with diarrhea-predominant irritable bowel syndrome. Its primary outcome uses baseline and post-treatment stool collections from the same participants. The registry also lists related biochemical and stool outcomes, but the primary measurement question concerns total 48-hour fecal bile acids.
The registry record does not report the numerical primary outcome. Without the mean change or its uncertainty, it is not possible to say whether the measured value increased or decreased, how large the change was, or how precisely it was estimated. The record therefore does not allow a conclusion about the observed responsiveness of the assay from the posted results. Completion status and the presence of an outcome definition do not substitute for the missing numerical result.
Even if a numerical before-and-after change were available, the single-group design would limit causal interpretation. A change during treatment would describe what happened in the observed group over time; absent a control group, it would not isolate the treatment's contribution from other possible influences. The record also does not provide a direct comparison of the HPLC method with another measurement method, so it does not establish relative assay accuracy, agreement, or reliability.
The primary outcome includes participants with complete measurements at baseline and after treatment. That population differs from the accrued study population as described in the registry, because one subject withdrew before treatment activities. The information does not establish whether the complete-data results would represent all accrued participants or whether additional missing data affected other outcomes.
The study's findings, as reported in the registry record, should therefore be understood as a study design and endpoint description with incomplete numerical outcome reporting. They do not establish that colesevelam does or does not produce a particular change, that the assay is suitable for every clinical or research use, or that treatment is better than an alternative. Those questions require information and comparisons not reported in the record.
13. Why This Trial Matters Statistically
This study is statistically notable because it separates two questions that can easily be conflated: whether a biological measure changes after treatment, and whether a measurement method can capture that change. The registered primary endpoint is a change in total 48-hour fecal bile acids measured by HPLC/tandem mass spectrometry. The stated aim is assay responsiveness in the context of colesevelam treatment, rather than a randomized comparison of treatment options.
The repeated measurement structure makes the participant the reference for their own baseline value. In general, this can focus an analysis on within-participant change, while also requiring an analysis that appropriately reflects the relationship between repeated observations. The registry record identifies the two measurement periods but does not report the statistical procedure used to analyze them. This makes the design understandable but leaves important details of estimation and uncertainty unavailable.
The record also illustrates why an outcome definition is not the same as an outcome result. It specifies the unit, summary measure, dispersion measure, collection timing, and complete-data population, but does not report the numerical primary finding. Without the estimate and its uncertainty, readers cannot judge magnitude, direction, or precision. Statistical interpretation depends on those values, not solely on the fact that the study was completed.
The study's single-group structure is another central issue. A before-and-after comparison can document change over the treatment period, but a separate randomized comparator would be needed to make a direct treatment comparison. The registry's planning illustration describes a two-arm equal-allocation setup, which is not the design listed for the completed study. Keeping planning assumptions separate from the actual design prevents an illustrative sample-size calculation from being mistaken for observed evidence or for the trial's own rationale.
Finally, the complete-data definition and limited safety reporting matter for transparency. The registry explains the withdrawal before treatment and specifies which participants contribute to the primary outcome, but does not describe broader missing-data methods. It reports adverse-event counts without a comparator. These features show why careful reading of population definitions, analysis plans, and numerical results is essential when interpreting a small before-and-after study.
14. 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.
A principal limitation is that the registry record does not report the numerical primary outcome or its uncertainty. Although the endpoint, units, measurement method, and timing are described, readers cannot assess the actual mean change, standard error, confidence interval, or statistical evidence. The central assay-responsiveness question therefore cannot be answered from the posted results in the registry record.
The single-group design has no randomized control group. Any measured change over time would not, on its own, separate a treatment-associated change from natural variability, time effects, or other influences. The registry also does not report a comparison between the HPLC method and another assay, so the study description alone does not establish comparative measurement performance.
The primary outcome includes 12 participants with complete baseline and post-treatment data, while the registry reports 13 subjects accrued and one withdrawal before treatment activities. The record does not report a broader missing-data strategy, sensitivity analysis, or analysis-population plan. The potential effect of incomplete data on interpretation cannot be assessed from the registry information.
The treatment and measurement period are limited to colesevelam at 1875 mg orally twice daily for 10 days, with the post-treatment collection during days 9-10. The registry does not describe longer-term measurements or follow-up. It also does not report the statistical procedure, assumptions assessment, adjustment strategy for the listed outcomes, or protocol-level sample-size justification.
Safety interpretation is limited by the single-group structure and the absence of a reported comparative group. Although the registry lists serious and other adverse-event counts, it does not provide descriptions for the other recorded events or report the death count. These limitations restrict the conclusions that can be drawn about both the measurement question and the broader clinical context.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ability of Mayo Clinic High-performance Liquid Chromatography (HPLC) Method to Measure Fecal Bile Acids — NCT02111603.
- Registry record last updated 2016-05-12; status last verified 2016-04.
- Results first posted 2016-01-27.
- 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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18. Record Summary
NCT02111603 is a completed Phase 4, single-group study sponsored by Mayo Clinic. It investigates whether a Mayo Clinic HPLC method can measure changes in fecal bile acids after colesevelam treatment in patients with diarrhea-predominant irritable bowel syndrome. The registry lists the start as 2014-04 and primary completion as 2014-08.
Participants received colesevelam at 1875 mg orally twice daily for 10 days. Total 48-hour fecal bile acids were measured by HPLC/tandem mass spectrometry at baseline and during days 9-10. The primary outcome is a mean change, with standard error specified as the dispersion measure. Thirteen subjects were accrued; one withdrew before treatment activities, and the primary outcome includes the 12 participants with complete measurements at both time points.
The registry lists five secondary outcomes in addition to the primary outcome. It reports 0 serious adverse events and 2 other adverse events among 12 at risk; the death count is not reported in the registry record. The numerical primary-outcome result, its uncertainty, and the detailed statistical analysis plan are not reported in the registry record.