A Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Parkinson's Disease (MAESTRO): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Parkinson's Disease (MAESTRO) (NCT02092181), a randomized phase 4 study. The primary outcome is Change in the Mean Daily Overactive Bladder-Symptom Composite Score..

2. Clinical Question

3. Trial Design

MAESTRO is a completed phase 4 study registered as NCT02092181. The registry describes a randomized, double-masked, parallel-group design and an enrollment of 30. The study started in 2014-03, and its primary completion date is listed as 2018-07-01. The named condition is Parkinsons Disease. Daniel Burdick, MD is listed as sponsor.

The two posted arms are Mirabegron and Placebo, each with 15 participants in the outcome summary. The arm descriptions state that participants were randomized 1:1 to mirabegron 25 mg daily or placebo at visit 2. They also describe a planned increase to mirabegron 50 mg daily at visit 3 for participants who tolerated mirabegron 25 mg daily. The placebo-arm description is truncated in the registry record, and actual dose exposure by participant is not reported. The record does not give enough information to reconstruct all treatment procedures.

The study title describes mirabegron and behavioral modification including pelvic floor exercise. The registry record does not clearly report the delivery, timing, or arm-specific use of that behavioral component, so it is not possible to characterize its implementation from the record. The primary outcome was change in mean daily Overactive Bladder-Symptom Composite Score from baseline at visit 2 to visit 4, over a stated timeframe of 7-82 days.

The record names four secondary outcomes: the Overactive Bladder Questionnaire Symptom Severity Scale, the Non-Motor Symptoms Scale, Patient Perception of Bladder Condition, and Subjects Global Impression of Change. It lists 7 outcome measures overall. Further protocol details, including eligibility criteria and the original statistical plan, 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.

Before assignment: Subjects who have met exclusion criteria.

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 Change in the Mean Daily Overactive Bladder-Symptom Composite Score., measured over 7-82 days. From visit 2 (baseline) to visit 4.

The primary endpoint is change in the mean daily Overactive Bladder-Symptom Composite Score (OAB-SCS) from baseline at visit 2 to visit 4. The registry gives a timeframe of 7-82 days. This continuous measure is based on participants’ ratings of urgency for each urination during a 72 hour recording period. Each episode is rated from 1 to 6, from “Not at all” to “A very great deal,” and the ratings are summed. The maximum possible total depends on the number of urination episodes recorded.

The endpoint is intended to capture both the severity of urgency and the burden across recorded episodes, rather than only whether urgency occurred. Higher scores indicate worse overactive bladder symptoms. A negative change therefore indicates that the score at follow-up was lower than at baseline; the magnitude of change must be read in light of the variability and uncertainty in the group comparison.

The outcome is reported as a mean, with standard deviations describing variation among participants. A mean provides a group-level summary of a continuous score, but does not describe every participant’s experience. The registry record does not report details of how incomplete 72-hour recordings or missing endpoint values were handled.

7. Results Posted in the Registry

• Mirabegron: mean -3.20 versus -8.90 on control; difference 5.70 (95% CI -0.14 to 11.54), standardized effect d = 0.70; z-test p = 0.056.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score that can take a range of values. The registry describes it as a mean with standard deviation. A group mean condenses the observed scores into a measure of central tendency, while the standard deviation describes how dispersed participant scores are around that mean. These summaries answer different questions. A similar mean can arise from a tightly clustered group or from a group with widely varying scores.

What does the mean difference represent?

The posted comparison expresses the mean difference as Mirabegron minus Placebo. The arm means are -3.2 and -8.9, respectively, and the posted difference is 5.7 units. Since the outcome is a change score, negative values mean the follow-up score was lower than baseline. Since higher OAB-SCS values indicate worse symptoms, a more negative change corresponds to a larger reduction in the recorded score. The sign of a difference must therefore be interpreted using both the order of subtraction and the direction of the scale.

A mean difference is a summary across groups. It does not mean that every participant had a change equal to the group mean, and it does not show the distribution of individual responses. The standard deviations of 8.4 and 7.9 indicate variation within the respective groups. Variation matters because it affects how precisely the difference in group means can be estimated.

How should the p-value be read?

The posted unadjusted p-value is 0.056. In general, a p-value measures how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not quantify the chance that the result is due to bias or error. The registry record does not report a complete statistical analysis plan, so the exact inferential procedure and its assumptions are not reported in the registry record.

The word “unadjusted” matters because the record lists several outcomes, while the multiplicity strategy is not reported in the registry record. An unadjusted p-value does not account for the possibility of testing multiple outcomes or comparisons. It should be read as the reported result for this comparison, not as a statement that all potential testing has been accounted for.

Why does the confidence interval matter?

A confidence interval gives a range of values compatible with the data under the method used to calculate it. The interval for the mean difference includes zero and extends to 11.54 at its upper limit. Values near zero represent little or no difference in the group means; values farther from zero represent larger differences. Because the interval includes zero, the posted result does not precisely distinguish a difference from no difference. The interval’s width is also relevant: it shows that the estimate is uncertain, even though the point estimate is 5.7.

General statistical interpretation distinguishes the point estimate from its precision. The point estimate gives one central summary of the observed difference, whereas the confidence interval conveys uncertainty around that estimate. Neither one alone establishes clinical importance. The registry record does not report a threshold for a meaningful difference on the OAB-SCS.

What do the standard deviations tell us?

The standard deviations describe how participant scores vary within each group, not the uncertainty in the mean difference by themselves. The two standard deviations, 8.4 and 7.9, are large in relation to the estimated difference of 5.7. With 15 participants in each posted arm, the estimate is based on limited group information. In general, high variability and small groups tend to make estimates less precise, although the actual precision should be judged from the reported confidence interval rather than inferred from any single summary statistic.

The posted comparison also includes an effect-size estimate, but it is not needed to interpret the clinical scale or the confidence interval. No adjusted estimate is reported in the registry record considered for this explanation. The registry record does not report whether covariates, repeated measurements, or other modeling choices were used in the sponsor’s analysis.

What can and cannot be inferred from the comparison?

The result is a comparison of mean changes in randomized groups as posted in the registry record. Randomization is a design feature intended, in general, to support a fair comparison by assigning participants to groups without choosing their assignment based on outcome-related characteristics. Masking is another design feature that can reduce some forms of influence on care or assessment. The record identifies the study as randomized and double-masked, but does not report enough implementation detail to evaluate how these procedures were carried out.

Interpretation also depends on what happened after randomization, including adherence, outcome availability, and analysis population. These details are not reported in the registry record. The posted summaries cannot establish whether all randomized participants contributed endpoint data or whether the groups were analyzed according to an intention-to-treat approach. The result should therefore be described as the registry’s posted comparison, with these reporting limits kept in view.

10. Confidence Intervals and Precision

The mean difference is 5.7 units, and the reported confidence interval runs from a slightly negative lower limit to 11.54. Because zero lies within the interval, the data do not rule out no difference in mean change. The same interval also permits positive differences extending to 11.54. The result is therefore not a sharply localized estimate of the between-group difference.

In general, a confidence interval is a way of expressing the uncertainty of an estimate under a statistical method and its assumptions. A narrower interval indicates greater precision; a wider interval indicates less precision. The interval should be read together with the point estimate rather than as a separate result. It describes uncertainty in the estimated group difference, not the range of individual participant changes.

The reported standard deviations are 8.4 for Mirabegron and 7.9 for Placebo, with 15 participants in each group. The group means are -3.2 and -8.9. These summaries show that participant-level scores vary within both arms, while the confidence interval conveys uncertainty about the difference between the arm means. The unadjusted p-value is 0.056, which is consistent with an interval that includes zero under the reported comparison.

The registry record does not report a clinically meaningful threshold for the OAB-SCS. Statistical precision and clinical importance are different questions: the interval describes uncertainty about the mean difference, while clinical interpretation requires context about what size of change matters. That context is not reported in the registry record.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning estimates are illustrations based on the observed effect, not the trial’s original design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The registry record does not report the original sample-size justification or the assumptions used when the trial was designed.

The estimates are participants per arm, not totals across both arms. For planning for 100% of the observed effect, the estimates are 33 participants per arm for 80% power and 44 participants per arm for 90% power. For planning for 75% of the observed effect, they are 58 participants per arm for 80% power and 77 participants per arm for 90% power. For planning for 50% of the observed effect, they are 129 participants per arm for 80% power and 173 participants per arm for 90% power.

In general, power is the probability that a study will detect an effect of a specified size under the assumed model, if that effect is present. The 80% and 90% columns describe different planning targets: the higher target requires more participants per arm for each listed effect. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants. The plotted planning curve should be read as a visual representation of this relationship between assumed effect size and required enrollment, not as evidence about what was achieved in this study.

These are planning illustrations, not observed power. They do not show the probability that the completed trial’s result is correct. Because the calculations use the observed effect as their reference, they should not be treated as an independent confirmation of the estimated effect.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 5.700; pooled standard deviation σ = 8.154.
2. n = 2 × (1.96 + 0.842)² × 8.154² / 5.700² = 32.1, rounded up to 33 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 5.7                      # observed difference in means
sigma <- 8.15383345427168                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2092181)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 33 (80% power), 44 (90% power)
 75% of observed effect: n per arm = 58 (80% power), 77 (90% power)
 50% of observed effect: n per arm = 129 (80% power), 173 (90% power)
power.t.test: 33.1 
Simulated power at n = 33 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists four secondary outcomes: Overactive Bladder Questionnaire Symptom Severity Scale, Non-Motor Symptoms Scale, Patient Perception of Bladder Condition, and Subjects Global Impression of Change. It lists 7 outcome measures overall. The multiplicity strategy—whether or how testing across outcomes was controlled—is not reported in the registry record. The posted primary comparison is described with an unadjusted p-value of 0.056, so it should not be read as adjusted for the full set of outcomes.

The record lists zero analyses, while the posted outcome information includes arm summaries and a comparison for the primary outcome. These entries do not provide a complete account of the analysis procedures. The registry record does not report the original statistical analysis plan, the model used by the sponsor, any interim analyses, or how analysis decisions were made. Those details are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The posted summaries give 15 participants in each arm, but do not establish whether every randomized participant posted the primary endpoint or how any absent measurements were treated. It is not possible to determine from these summaries whether imputation was used, whether incomplete diaries were excluded, or whether sensitivity analyses were conducted.

The analysis population is not reported in the registry record. The summaries do not specify whether the comparison included all randomized participants, only participants who completed follow-up, or another defined group. The record also does not report a protocol-deviation strategy or the handling of treatment changes. These omissions limit assessment of how the randomized design was reflected in the final analysis, and make it important to distinguish the posted numerical comparison from a fully documented analysis plan.

14. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: psychosis (6.7%), cellulitis (6.7%), pneumonia (6.7%).

The registry reports serious adverse events for groups of 15 participants in each arm. In the Mirabegron group, 0 participants were listed as affected by a serious adverse event; in the Placebo group, 1 participant was listed as affected. The registry also lists no deaths in either group. These are counts in the posted record and should be read as descriptive safety information, not as proof that a treatment caused or prevented an event.

The serious-event terms listed are Psychosis, Cellulitis, and Pneumonia, each reported as 6.7%. The registry entries do not identify an arm for each term or clarify the relationship between the terms and the participant-level serious-event counts. No further event narratives or causal assessments are reported in the registry record.

Other adverse events are listed for 9 participants in the Mirabegron group and 6 in the Placebo group, with 15 participants at risk in each group. These counts do not describe event severity, timing, or whether participants experienced more than one event. The registry record does not provide enough detail to interpret the full safety profile or to compare event types and exposure periods.

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

The posted primary outcome summaries show mean changes of -3.2 units for Mirabegron and -8.9 units for Placebo, with a mean difference of 5.7 units and an unadjusted p-value of 0.056. The reported confidence interval includes zero and extends to 11.54 on its upper side. These findings describe a difference in average change in the recorded urgency score, with uncertainty that includes no difference.

The outcome measures urgency ratings over a 72 hour recording period, and higher total scores indicate worse symptoms. The posted result therefore concerns this particular score over the stated timeframe of 7-82 days, from baseline at visit 2 to visit 4. It does not describe every aspect of overactive bladder, Parkinson’s disease, or participants’ daily experience.

The result does not establish that mirabegron works or does not work. It is a small pilot comparison, and the estimate is imprecise. The record does not report a threshold for a clinically meaningful score difference, so statistical summaries alone cannot determine the importance of the observed point estimate. The primary outcome also cannot substitute for results on the four listed secondary outcomes, which are not included in the registry record.

The registry identifies the study as randomized and double-masked, but does not report full implementation details, missing-data methods, analysis populations, or the original statistical plan. Those limitations affect how thoroughly the comparison can be assessed. Safety counts are likewise descriptive and do not establish that an event was caused by a study treatment.

The appropriate reading is therefore bounded: these are posted group-level changes and an uncertain comparison at the specified follow-up. The results do not establish durability beyond visit 4, individual response patterns, or effects on outcomes not reported in the registry record.

16. Why This Trial Matters Statistically

This study illustrates why a clinical comparison should be read through more than its point estimate. The difference in mean change is 5.7 units, but the confidence interval includes zero and reaches 11.54 at its upper limit. The interval communicates uncertainty that is not conveyed by the point estimate alone. The unadjusted p-value of 0.056 is another summary of the comparison, but it does not replace the interval or explain whether the difference is important to patients.

It also highlights the role of outcome definition. The primary score is built from severity ratings for urgency at each urination across a 72 hour recording period, with a total dependent on the number of recorded episodes. Higher values indicate worse symptoms. Understanding that construction is necessary to interpret the sign of the change and the meaning of a group difference.

The pilot scale of the study matters statistically. The outcome summaries include 15 participants per arm, and the standard deviations are 8.4 and 7.9. In a small study with variable scores, estimates can remain uncertain even when a numerical difference is observed. The planning illustrations further show that required participants per arm increase when the assumed effect to detect is smaller, but those calculations do not represent the study’s original planning process or its achieved power.

Finally, the registry record demonstrates the importance of transparent methods reporting. The original sample-size justification, multiplicity strategy, missing-data handling, analysis populations, and detailed analysis plan are not reported in the registry record. Without those details, readers can describe the posted comparison but cannot fully assess how the analysis was conducted or how robust it may be to alternative assumptions.

17. 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.

Several limitations specific to this trial constrain interpretation. The study enrolled 30 participants, with 15 reported in each arm for the primary outcome. That is a limited basis for estimating a group difference, particularly given the standard deviations of 8.4 and 7.9. The confidence interval includes zero and extends to 11.54, indicating uncertainty about both the direction and size of the mean difference.

The primary score is based on urgency ratings recorded over a 72 hour period, and the maximum total depends on the number of urination episodes. The registry record does not report how incomplete diaries, missing ratings, or missing follow-up scores were handled. It also does not report the analysis population, so the relationship between enrollment and the participants contributing to the posted endpoint summaries is not fully described.

The record’s arm descriptions are truncated. Although they describe random assignment to mirabegron 25 mg daily or placebo and a planned dose increase for participants tolerating the initial mirabegron dose, actual dose exposure is not reported. The study title refers to behavioral modification including pelvic floor exercise, but the registry record does not clearly explain how that component was implemented or whether it differed between arms.

The original sample-size assumptions and statistical analysis plan are not reported in the registry record. Multiplicity handling, interim analyses, and the treatment of protocol deviations are also not reported. The posted unadjusted primary comparison therefore cannot be assessed against a fully documented analysis plan. The record lists secondary outcomes, but their results are not included in the registry record, and it does not report a clinical-importance threshold for the primary scale.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Pilot Study of Mirabegron and Behavioral Modification Including Pelvic Floor Exercise for Overactive Bladder in Parkinson's Disease (MAESTRO) — NCT02092181.
• Registry record last updated 2021-08-16; status last verified 2021-07.
• Results first posted 2021-08-16.
• 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.

21. Record Summary

MAESTRO (NCT02092181) is a completed phase 4, randomized, double-masked, parallel-group pilot study of mirabegron and placebo for overactive bladder symptoms in Parkinson’s disease. The registry lists enrollment of 30, a start date of 2014-03, and primary completion on 2018-07-01.

The primary outcome is change in mean daily OAB-SCS from baseline at visit 2 to visit 4, over 7-82 days. Mean changes were -3.2 in the Mirabegron group and -8.9 in the Placebo group. The posted mean difference was 5.7 units, with a confidence interval including zero and an unadjusted p-value of 0.056.

The registry lists four secondary outcomes and reports descriptive adverse-event counts. The original design assumptions, detailed analysis plan, multiplicity approach, missing-data methods, and analysis populations are not reported in the registry record.