Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action (NCT01990898), a na phase 2 study. The primary outcome is Symptom Improvement of Interstitial Cystitis.

2. Clinical Question

This question is about the number of participants crossing a prespecified symptom-improvement threshold, rather than the average change in symptom score. The ICSI is described as a scale from 0 to 19, with higher scores indicating worse symptoms. However, the record does not report participants’ scores at the start or end of the study, the change in scores, or the number meeting the improvement threshold.

Because there is no concurrent comparator, the study cannot directly estimate how the observed outcome would differ from an outcome under another treatment or no study treatment. Its design is suited to documenting outcomes among participants receiving cyclosporine, but any treatment-effect comparison would require information beyond this single-group record.

3. Trial Design

This completed phase 2 study examined cyclosporine for interstitial cystitis. The registry record lists a single-group model, allocation as not applicable, and no masking. It records enrollment of 26 and identifies The Cleveland Clinic as the sponsor. The study start is recorded as 2013-11 and primary completion as 2015-10.

Participants received cyclosporine in pill form. The registry description says dosage was calculated at study visits, treatment was taken twice daily, and the duration was 3 months. The study summary describes patients who had tried at least two different therapies unsuccessfully. The registry record does not report further eligibility criteria, the dose range, or how dose adjustments were made.

A single-group design has no concurrent control group to distinguish the course of symptoms during treatment from what might have occurred without the intervention or with another intervention. No random allocation or masking is reported. These features matter when interpreting subjective symptom outcomes: changes in reported symptoms cannot be attributed to the intervention solely from the design described in this record.

The registry lists one outcome measure, symptom improvement at 3 months, expressed as a participant count. It says no additional analyses have been done. The observed primary outcome count, a statistical estimate of uncertainty, baseline symptom summaries, and details of the analysis population are not reported in the registry record. The registry also does not report a protocol, a statistical analysis plan, a sample-size justification, or interim analyses. The study status is completed, but completion status alone does not establish what the outcome was.

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

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 Symptom Improvement of Interstitial Cystitis, measured over 3 Months.

The primary endpoint counts participants with more than 30% improvement in the Interstitial Cystitis Symptom Index at 3 months. The ICSI is described as a scale from 0 to 19, where higher values indicate worse symptoms. This endpoint therefore classifies participants according to whether their symptom improvement passes a specified threshold; it is not a report of the average score or average score change.

A threshold-based outcome can be easy to interpret as a count of participants meeting a defined criterion. It also discards detail: participants just below and just above the threshold are placed in different categories, while differences among participants within either category are not captured by the count. The registry record does not explain why this threshold was selected, whether it was defined before outcome data were examined, or whether changes in the underlying score were also assessed.

The outcome is listed at 3 months, matching the stated treatment duration. The registry record describes the endpoint but does not report the number meeting the threshold, the number assessed at that time, or an uncertainty interval. It also does not report how missing endpoint measurements were handled. Without those details, the endpoint’s observed frequency and precision cannot be evaluated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a binary primary outcome: a participant is counted if ICSI improvement exceeds the stated threshold at 3 months. It reports no additional analyses. No estimate, confidence interval, hypothesis test, or detailed statistical method for this endpoint is reported in the registry record. The explanations below describe general statistical principles that help readers understand this kind of outcome; they are not claims about analyses performed in this study.

What does a binary endpoint represent?

A binary endpoint places each assessed participant into one of two categories, such as meeting or not meeting an improvement criterion. The resulting count depends on both the number meeting the criterion and the number whose outcome was assessed. Reporting a count without its denominator does not show the proportion of the analyzed group meeting the criterion. Reporting a proportion without its denominator or uncertainty also gives an incomplete picture, particularly when the group is small.

Thresholds can make results straightforward to communicate, but they compress information. A participant’s exact score change is not conveyed by whether the threshold was crossed. A complete account might also report the score distribution or change in the underlying scale, but such results are not reported in the registry record.

Why does uncertainty matter?

A result calculated from a study group is subject to sampling variability: a different group of eligible participants might produce a different observed count. A confidence interval is a general way to express the range of values reasonably compatible with the observed data under a specified statistical method. Its width reflects precision; a wider interval indicates greater uncertainty. The registry record does not report a confidence interval or enough endpoint results to assess one.

A significance test, when appropriate and prespecified, addresses a question framed by a null hypothesis. Its p-value does not measure the size or clinical importance of an effect, and it does not establish causation. No p-value or hypothesis test for the primary outcome is reported. In a single-group study, a test against a fixed reference would answer a different question from a randomized comparison, and the registry does not report such a test.

What does the design allow?

In a randomized comparison, allocation can support a like-for-like contrast between groups, subject to the trial’s conduct and analysis. This study is listed as single-group, with allocation not applicable and no masking. It therefore does not offer a concurrent randomized contrast. General sources of uncertainty in an uncontrolled study include changes over time, co-occurring care, expectations, and who remains available for outcome assessment. The registry record does not report whether or how these factors were addressed.

Masking is a general method for reducing the influence of knowledge about treatment assignment on care, measurement, or reporting. The registry lists masking as none. Since the primary endpoint is based on a symptom index, expectations or knowledge of treatment could matter in principle; the record does not report an assessment of this possibility. This is a design consideration, not proof that the symptom reports were biased.

How should planning illustrations be read?

Sample-size calculations are planning tools, not trial results. A planning illustration based on an observed effect is not the same as a sample-size justification documented before a trial, and it is not observed power. The registry record does not report the trial’s own sample-size justification or statistical plan. It describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. Those assumptions describe an illustration; they do not change this study’s single-group design or create a comparator that was not present.

In general, over-dispersion means that observed variation is greater than a model assumes. If it is ignored, standard errors can be too small and intervals or tests can overstate precision. The registry record does not report an over-dispersion analysis or a model for the primary outcome. For a simple binary count, the exact method and its assumptions would depend on the analysis being conducted; no such method is stated for this endpoint.

What information is needed to evaluate an analysis?

Readers would need the endpoint count, the number assessed, the handling of missing outcomes, and the analysis population to understand the reported result. To evaluate reproducibility, they would also need the prespecified analysis methods and any departures from them. These details are not reported in the registry record. The record states that no additional analyses have been done, so it does not offer a reported inferential analysis to interpret.

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("Treatment")
n      <- c(22)
events <- c(9)
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  Treatment  22  9  40.9  20.7  63.6  23.3  61.3  23.2  61.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and says no additional analyses have been done. It does not report a multiplicity adjustment or describe a plan for controlling the chance of false-positive findings across multiple outcomes or tests. With a single listed primary measure, the extent of any multiplicity concern cannot be assessed from the registry alone; unreported analyses or outcomes should not be assumed.

Missing data are important for a participant-count endpoint because the denominator should reflect who had an outcome assessment at 3 months. Enrollment is recorded as 26, but the number assessed for the primary endpoint is not reported in the registry record. The record also does not say whether anyone discontinued, whether any ICSI values were missing, or how missing values were handled. It is therefore not possible to tell whether the endpoint count, if reported elsewhere, would include all enrolled participants or a subset.

Analysis populations are also not described. The registry record does not state whether the endpoint was analyzed among all enrolled participants, those who began treatment, those who completed treatment, or another defined group. These are general distinctions: different analysis populations can yield different estimates, especially when follow-up is incomplete. No assumptions about imputation, exclusions, or sensitivity analyses are reported. The result and its robustness to missing data cannot be assessed from the information recorded.

12. Safety Results

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

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 lists 0 serious adverse events among 26 participants at risk in the treatment group. It lists 2 other adverse events among 26 participants at risk. The serious-event terms field contains no listed terms. Deaths are not reported in the registry record.

These entries are registry counts, not a comparison with another treatment: the study had a single group. The record does not describe the events, their timing, severity apart from the serious-event classification, relationship to cyclosporine, or whether any participant experienced more than one event. The distinction between the listed serious and other adverse events should be retained; the other-event count should not be relabeled as serious events.

A count of zero recorded serious adverse events does not establish that no harms occurred or that the treatment is safe. It describes only what is entered in this registry record, within the recorded group and reporting categories. The record does not provide enough detail to evaluate completeness of safety reporting or compare risks across interventions.

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

This record establishes that a completed phase 2, single-group study examined cyclosporine in interstitial cystitis and specified a symptom-improvement endpoint at 3 months. It also records the treatment schedule and certain adverse-event counts. It does not report the primary endpoint result, so it does not show how many participants met the improvement criterion.

The missing endpoint count should not be interpreted as no improvement, and it should not be interpreted as improvement. Completion status means that the study is recorded as completed; it does not supply the missing outcome result. Because the registry also reports no additional analyses, there is no stated statistical estimate or test of the primary outcome to interpret.

Even if a symptom-improvement count were available, the single-group design would limit conclusions about treatment effects. Without a concurrent comparator, observed changes could not be separated cleanly from other influences on symptoms. This is a general limitation of uncontrolled studies, not a claim about what happened to participants in this study. The record also does not report the analysis population, endpoint missingness, or methods for handling it.

The adverse-event entries likewise have a limited meaning: the registry records 0 serious adverse events and 2 other adverse events in the treatment group, while deaths are not reported. Without event descriptions or a comparison group, these counts cannot establish comparative safety or characterize the full safety profile.

The appropriate conclusion is therefore about the record’s scope: it describes the study design, intervention, and intended primary outcome, but leaves the primary outcome result and key analysis details unreported. No treatment-effect conclusion can be drawn from the endpoint description alone.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between a clearly defined outcome and a reported result. The registry specifies a threshold-based symptom endpoint, its scale, and its time point. Yet it does not report the count of participants meeting the threshold or an analysis of that count. A prespecified-sounding endpoint description is not a substitute for observed data, a denominator, or an uncertainty estimate.

The design also shapes what can be learned. A single-group study can document outcomes among people receiving an intervention, but it lacks the concurrent comparison needed to estimate a treatment contrast directly. This matters especially for symptom outcomes, which may be affected by factors other than the intervention. No randomized comparison or masking is reported in the registry record.

The safety record shows why event categories and denominators should be read carefully. Serious and other adverse events are listed separately, and the record includes no descriptions of the events. Counts alone do not provide a comparative risk estimate or a complete account of adverse-event experience.

Finally, the record highlights the difference between planning and inference. A planning illustration based on an observed effect is not evidence that the planned comparison occurred, and it is not observed power. The registry record does not report a trial-specific sample-size justification or analysis plan. For researchers and clinicians reading registry entries, the central statistical task is to distinguish the intended question from the results actually reported, and to distinguish descriptive counts from causal comparisons.

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 leaves several trial-specific limitations unresolved. It describes a single-group study with no allocation and no masking, so there is no concurrent control for interpreting symptom changes. The record does not report a comparator, randomization procedure, or blinded outcome assessment. These omissions prevent a direct treatment contrast and make it difficult to judge how symptom reporting may have been influenced by the open-label design.

The primary endpoint is described, but its observed count is not reported. The record gives no endpoint denominator, ICSI baseline or follow-up summaries, or estimate of uncertainty. It also does not report the analysis population, withdrawals, missing outcome data, or how missingness was handled. These gaps prevent assessment of the result’s magnitude, precision, and sensitivity to incomplete follow-up.

The registry says no additional analyses have been done, and it does not report a statistical analysis plan, a trial-specific sample-size justification, or interim analyses. The rationale for the improvement threshold is not reported in the registry record. The safety information is limited to categorized counts, with no event descriptions; deaths are not reported. These are limitations of the available registry record and should not be taken as proof that further information does not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action — NCT01990898.
• Registry record last updated 2017-04-19; status last verified 2016-10.
• Results first posted 2017-04-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed phase 2 study of cyclosporine for interstitial cystitis. It is listed as a single-group study, with allocation not applicable and no masking. Enrollment is recorded as 26. Cyclosporine was administered in pill form, twice daily for 3 months, with dosage calculated at study visits.

The primary outcome was the number of participants with more than 30% improvement in ICSI at 3 months. The scale is described as ranging from 0 to 19, with higher scores indicating worse symptoms. The record reports no additional analyses, and the primary endpoint count is not reported in the registry record.

For safety, the treatment group lists 0 serious adverse events and 2 other adverse events; deaths are not reported. The study start is recorded as 2013-11, primary completion as 2015-10, and status as completed.