Interstitial Cystitis: Examination of the Central Autonomic Network: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Interstitial Cystitis: Examination of the Central Autonomic Network (NCT03008382), a randomized phase 4 study. The primary outcome is Total Score on Genitourinary Pain Index (GUPI) Scale.

2. Clinical Question

3. Trial Design

The registry record describes a completed phase 4, randomized, double-masked, crossover study sponsored by Virginia Commonwealth University. Its listed enrollment is 72. The study started on 2017-03-01, and its primary completion date is 2022-03-16. The conditions listed are Interstitial Cystitis/Painful Bladder Syndrome and Myofascial Pelvic Pain.

For the chronic pelvic pain group, participants were randomized to treatment order. One sequence was 8 weeks of Metoprolol Tartrate Oral Tablet, a 4-Week washout period, and then 8 weeks of Placebo Oral Tablet. The other sequence reversed the order. This structure allows the treatment periods to be compared while accounting for the fact that the same participant receives both treatments. That is a general feature of crossover designs; the registry record does not specify the statistical model used to account for the repeated measurements or treatment sequence.

The healthy control group had a different role. Its description identifies healthy female subjects ages 18-80 and states that they would not receive randomization or drug treatment during the study. The record also lists an observational sub-study with no intervention. These groups should not be treated as randomized arms in the metoprolol-versus-placebo comparison.

The registry lists Metoprolol Tartrate Oral Tablet, Placebo Oral Tablet, and a no-intervention observational sub-study. Although the study status is completed, completion status alone does not show whether the primary outcome favored either treatment. The registry record does not report outcome estimates or an outcome analysis.

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: Participants enrolled into the Chronic Pain Group were randomized into 2 sequences or were enrolled into the observational study group: "Metopropol then Placebo," "Placebo then Metopropol OR "Observational Participants." The "participant flow" and "baseline characteristics" sections for the Chronic Pain Group are presented per sequence.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This assessment was not administered to all participants at each time point.

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 Total Score on Genitourinary Pain Index (GUPI) Scale, measured over Weeks 4, 12 and 24.

The primary endpoint is the total score on the Genitourinary Pain Index (GUPI). The registry record defines it as the sum of scores from the pain, urinary, and quality-of-life subscales. Individual questions do not have uniform score ranges, and the total score can range from 0-45. Higher scores indicate more female urinary symptoms.

The GUPI is used to measure symptoms relevant to genitourinary pain and urinary problems in the population under study. Combining the subscales into a total score gives a single continuous measure for describing participants’ reported symptom burden. The record specifies that the endpoint is summarized as a mean with standard deviation.

Scores were scheduled at weeks 4, 12 and 24, described respectively as baseline, post-first intervention, and post-second intervention. However, the registry record says the assessment was not administered to all participants at each time point. It does not report the observed means, standard deviations, or treatment comparison. Consequently, the endpoint definition explains what was intended to be measured, but does not establish how scores changed or how precisely any treatment difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical challenge is that this is a crossover study with repeated outcome measurements, rather than a simple comparison of separate treatment groups at a single occasion. The registry record identifies random allocation to treatment order and a washout period, but does not report the statistical analysis plan or results. The explanations below are general and describe considerations for this design; they should not be read as a claim that a particular method was used.

What does a crossover comparison mean?

In a crossover design, the same participant receives each treatment in sequence. A treatment comparison can therefore be based on within-participant information, which may reduce the influence of characteristics that remain stable within a person. However, measurements from the same participant are related, not independent. A suitable analysis needs to reflect that dependence rather than treat every measurement as though it came from a different person.

Here, the record describes randomized treatment order, a 4-Week washout period, and GUPI assessments at baseline and after each intervention. The record does not state how the analysis handled treatment period, sequence, baseline values, or possible carryover from the first treatment period into the next. A washout is part of the stated design, but its presence alone does not demonstrate that carryover was absent.

What does a mean and standard deviation describe?

The registered outcome is continuous and is described using a mean and standard deviation. In general, the mean describes the center of the observed scores, while the standard deviation describes their spread around that center. These summaries can help characterize a group’s observed scores, but they do not by themselves quantify the uncertainty in a treatment comparison. A confidence interval for a treatment effect would show a range of values compatible with the data and analysis assumptions. The registry record does not report such an interval for the GUPI comparison.

A treatment-effect estimate and its uncertainty are needed to assess both the size of an observed difference and its precision. A p-value, if reported, would address compatibility with a specified null hypothesis under the analysis assumptions; it would not convey the size or clinical importance of an effect. No outcome p-value or treatment-effect estimate is reported in the registry record.

Why can over-dispersion matter?

Over-dispersion is a general issue when observed variability is greater than a statistical model assumes. If a model understates variability, uncertainty can be understated and inference can become too confident. For a continuous endpoint, the model should reflect the actual distribution and dependence structure of the measurements. The registry record does not describe a model, report an over-dispersion assessment, or provide results that would permit such a check.

What can the planning assumptions tell readers?

General sample-size planning uses assumptions about the effect to detect, variability, allocation, and statistical testing. The record describes a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says the effect considered is a stated fraction of the observed effect. Such a calculation is a planning illustration, not observed power and not evidence that the trial detected an effect. A sample-size illustration cannot replace the observed treatment estimate and its uncertainty.

The registry record does not report the trial’s own sample-size justification or the statistical plan used for the primary outcome. It also does not state whether interim analyses were conducted. Those omissions prevent readers from checking whether the reported analysis, had it been posted, followed a prespecified plan. No primary outcome analysis is listed in the registry record.

How should the healthy controls be treated analytically?

The healthy control group was not randomized to metoprolol or placebo and did not receive study drug treatment. It is therefore distinct from the randomized crossover treatment comparison. General comparisons between a clinical group and healthy controls answer a different question from a randomized treatment contrast and can be affected by differences in group composition. The registry record does not report such an analysis or explain how the observational participants were included in any outcome analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was measured at weeks 4, 12 and 24, with the latter assessments described as following the first and second interventions. Multiple time points create choices about which comparison is primary, how repeated measurements are modeled, and whether results at different times are interpreted separately or jointly. The registry record gives the measurement schedule but does not report a statistical plan specifying those choices.

The record lists four outcome measures, but it does not describe a multiplicity adjustment or explain how conclusions across outcomes and time points would be controlled. Multiplicity is a general concern when several statistical comparisons are considered: without a prespecified approach, the chance of at least one apparently notable result can increase. That general issue does not establish that an inappropriate analysis occurred; the relevant analysis is not reported in the registry record.

Missing outcome information is also important. The registry record states that the GUPI assessment was not administered to all participants at each time point. It does not give the number of assessments available for each treatment period or time point, reasons for missing assessments, or the method used to handle missing values. It also does not state whether the analysis followed an intention-to-treat, per-protocol, or another population definition. These details are needed to understand who contributed to an analysis and how incomplete measurements affected the estimate.

The registry record does not report interim analyses or the primary outcome analysis. It therefore cannot establish whether multiplicity, missing data, or analysis-population decisions were addressed according to a prespecified plan. These are uncertainties about the available reporting, not proof that the study team failed to consider them.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports zero serious adverse events affected in each listed group and zero deaths in each listed group. For serious adverse events, the numbers listed as at risk are 43 for Metoprolol, 42 for Placebo, 45 for Baseline Period, 40 for Washout Period, 4 for Observational Participants, and 23 for Healthy Control. These are the registry’s group-specific counts; the groups represent different treatment or study periods and should not be treated as independent arms of a single parallel-group safety comparison.

The record also distinguishes other adverse events from serious adverse events. Other adverse events affected 22 in the Metoprolol group, 25 in the Placebo group, 5 in the Baseline Period, 4 in the Washout Period, and 0 in each of the Observational Participants and Healthy Control groups. Those counts should not be confused with serious events.

Zero reported serious events means none were recorded in the listed group entries; it does not prove that risk is absent. The record does not provide event-level descriptions for serious events, and the serious-event terms list is empty. Because the crossover groups and periods do not represent a simple parallel comparison, the counts alone do not establish whether one treatment has a different safety profile. They also do not substitute for the missing GUPI outcome analysis.

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

The registry record establishes that the study was designed to examine metoprolol and placebo in a randomized crossover among participants with chronic pelvic pain, with a GUPI score as the primary outcome. It also documents a healthy control group that did not receive study treatment. These design details clarify the question the study set out to address, but they are not findings about treatment effects.

No GUPI group summaries, treatment-effect estimate, confidence interval, or outcome p-value are reported. It is therefore not possible to say from the registry record whether scores differed between metoprolol and placebo, in which direction they differed, or how precisely any difference was estimated. The registry’s completed status should not be interpreted as evidence that a treatment effect was present or absent.

The reported adverse-event counts describe events recorded in treatment groups and study periods. They are not a direct measure of symptom improvement, and zero serious events recorded does not prove there is no risk. Nor do the listed counts, by themselves, establish a comparative safety advantage.

In general, a randomized crossover can help compare treatments within the same participants, but interpretation depends on the analysis, missing assessments, and assumptions about period and carryover effects. The registry record does not report enough information to evaluate those aspects of the primary outcome analysis. The appropriate conclusion is therefore limited: the record describes the design, endpoint, and safety counts, but does not provide the primary outcome results needed to judge the treatment comparison.

This is not a conclusion that metoprolol is effective or ineffective. It is a statement about what the registry record reports and the limits imposed by the absence of outcome estimates and analysis details.

13. Why This Trial Matters Statistically

This trial is statistically notable for its randomized crossover design. Rather than assigning participants with chronic pelvic pain to remain in a single treatment group, the design assigned treatment order so that participants received metoprolol and placebo in sequence. In general, this permits comparisons that use measurements from the same participant, but it also makes the analysis dependent on correctly accounting for repeated observations and treatment periods.

The study also includes a healthy control group and an observational sub-study. Keeping those groups distinct from the randomized crossover comparison is important: they did not undergo the same treatment assignment, so their role is not interchangeable with that of the metoprolol and placebo periods.

The primary endpoint combines pain, urinary, and quality-of-life subscales into a continuous GUPI total score. A total score can provide a compact measure of symptom burden, while requiring careful interpretation of the scale and the pattern of missing assessments. The registry record states that not all participants completed the assessment at every time point, making the analysis population and handling of missing measurements important considerations.

Most importantly, the registry record demonstrates why design details and outcome reporting must be read separately. A randomized, double-masked design describes how the comparison was intended to be conducted. It does not, on its own, supply an effect estimate or show how precisely an effect was measured. Without the primary outcome analysis, readers cannot assess the magnitude, direction, or uncertainty of the treatment comparison.

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.

The most consequential limitation in the registry record is the absence of primary outcome results. Although the GUPI endpoint, measurement schedule, and scoring direction are described, no outcome means, standard deviations, treatment-effect estimate, confidence interval, or p-value are reported. The treatment comparison therefore cannot be interpreted from this record.

Outcome availability is also incomplete by design or reporting: the record says the GUPI assessment was not administered to all participants at each time point. It does not identify how many assessments were available at each time or explain reasons for missing assessments. Missing-data methods and the analysis population are not reported, so the potential effect of incomplete outcome measurement cannot be evaluated.

The crossover design requires attention to within-participant dependence and possible period, sequence, or carryover effects. The record describes randomized treatment order and a washout period, but does not report the statistical model or how those design features were handled. The analysis plan, multiplicity strategy, and interim-analysis information are also not reported in the registry record.

The healthy control group and observational participants did not receive randomized treatment, so their observations cannot be interpreted as though they were part of the randomized metoprolol-versus-placebo comparison. Finally, the adverse-event counts are reported across treatment groups and periods, but the record does not provide detail that would support a full comparative safety analysis. These are limitations of what can be concluded from the registry record, not evidence that unreported procedures were or were not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Interstitial Cystitis: Examination of the Central Autonomic Network — NCT03008382.
• Registry record last updated 2025-02-17; status last verified 2025-02.
• Results first posted 2025-02-17.
• 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.

18. Record Summary

The registry record describes a completed phase 4, randomized, double-masked crossover study sponsored by Virginia Commonwealth University. Its listed enrollment is 72. Participants with chronic pelvic pain were assigned to treatment sequences involving Metoprolol Tartrate Oral Tablet and Placebo Oral Tablet, separated by a 4-Week washout period. Healthy controls received neither randomization nor study drug treatment.

The primary endpoint is total GUPI score at weeks 4, 12 and 24, with higher scores indicating more female urinary symptoms. The record states that the assessment was not administered to all participants at every time point. It reports zero serious adverse events affected and zero deaths in every listed group, alongside counts of other adverse events. It does not report the primary outcome results, treatment-effect estimate, or outcome analysis. Accordingly, the registry record describes the intended comparison but does not establish its result.