Multiple Dose Study To Investigate The Effects Of Fesoterodine And Solifenacin On Gastrointestinal Transit: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multiple Dose Study To Investigate The Effects Of Fesoterodine And Solifenacin On Gastrointestinal Transit (NCT00832650), a randomized phase 1 study. The primary outcome is Colonic Transit at 24 Hours.

2. Clinical Question

These are related but distinct questions: the brief summary names the active-treatment comparison, while the posted primary endpoint results include group means for all three arms and re-calculated comparisons of each active arm with placebo. The registry’s reported ANCOVA analysis compares the two active arms, but its result is an adjusted least-squares mean difference rather than the unadjusted mean differences calculated from the posted arm summaries. The distinction matters when reading the estimates: each addresses a different contrast and uses a different analysis approach.

The endpoint is a continuous weighted measure of where colonic counts are located. Its value is not a direct count of bowel movements or a clinical outcome. The registry record does not report a threshold defining a meaningful difference in this measure, or a separate clinical interpretation of a change in its geometric centre.

3. Trial Design

This was a randomized, triple-masked, parallel-group phase 1 study, with placebo, fesoterodine and solifenacin arms. The registry lists an enrollment of 60 and identifies healthy subjects as the condition. The official title specifies healthy female subjects, multiple dosing, and the 8 mg and 10 mg active regimens. The study was sponsored by Pfizer. Its status is recorded as terminated.

The registry lists the start as 2009-04 and primary completion as 2009-12. It does not report the reason for termination in the information summarized in the record. Nor does the registry record report the original planned allocation ratio, intended duration of follow-up, or the original sample-size justification. Although group sizes are posted for the primary outcome, they should not be taken as evidence of the original design assumptions.

Primary outcome group sizes were 25 for fesoterodine, 12 for placebo and 23 for solifenacin. These counts sum to the recorded enrollment, but the registry’s stated analysis population and imputation procedure still matter: it says the intent-to-treat population included all randomized subjects and missing data were imputed by the overall mean. The record does not provide additional detail about the amount or pattern of missing outcome data, or how many observations were imputed.

Randomization and masking are design features intended to reduce systematic differences and expectations that could affect assessments. The record labels the study triple masked but does not identify the specific roles or parties covered by that label. The parallel-group model means participants were assigned to one arm rather than crossing over among treatments; a more detailed description of the sequence of dosing and assessments is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) included all randomized subjects. Imputation by overall mean for missing data.

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 Colonic Transit at 24 Hours, measured over Day 13 (Day 12 24 hours post-meal).

The primary endpoint was colonic transit at 24 hours, measured on Day 13 (Day 12 24 hours post-meal). The registry describes the value as the geometric centre at 24 hours, or GC24, calculated from counts in the ascending, transverse, descending and rectosigmoid colon and stool. Each region is assigned a weight from 1 to 5, respectively, and the weighted proportions are combined to produce the score.

As a general statistical interpretation, a weighted location measure condenses information about where material is distributed across several ordered regions into one continuous value. That makes it possible to compare group averages using a single endpoint rather than treating every region as a separate outcome. In this measure, lower weights correspond to more proximal regions and higher weights to more distal locations, including stool. The endpoint is therefore a score of distribution, not a direct measure of transit time in hours.

The registry reports the outcome as a mean with standard deviation. It identifies the intent-to-treat population as all randomized subjects and states that missing data were imputed by the overall mean. The record does not report a clinically important difference for GC24, a threshold for categorizing individual participants, or an explanation of how the measure should be translated into patient experience. Its use supports a statistical comparison of measured distribution, but does not by itself establish the clinical importance of any difference.

7. Results Posted in the Registry

• Fesoterodine: mean 1.98 versus 2.51 on control; difference -0.53 (95% CI -1.21 to 0.15), standardized effect d = -0.60; z-test p = 0.127.
• Solifenacin: mean 1.91 versus 2.51 on control; difference -0.60 (95% CI -1.25 to 0.05), standardized effect d = -0.80; z-test p = 0.068.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Proximal Colonic Emptying Time

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Fesoterodine: mean 21.06 versus 14.79 on control; difference 6.27 (95% CI 2.13 to 10.41), standardized effect d = 1.09; z-test p = 0.003.
  • Solifenacin: mean 19.23 versus 14.79 on control; difference 4.44 (95% CI 0.10 to 8.78), standardized effect d = 0.72; z-test p = 0.045.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Fesoterodine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Solifenacin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Colonic Transit at 48 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Fesoterodine: mean 3.55 versus 3.67 on control; difference -0.12 (95% CI -0.83 to 0.59), standardized effect d = -0.12; z-test p = 0.739.
  • Solifenacin: mean 3.14 versus 3.67 on control; difference -0.53 (95% CI -1.21 to 0.15), standardized effect d = -0.60; z-test p = 0.126.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Fesoterodine and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Solifenacin and the control. The interval gives the range of effects that remain compatible with the data.

Colonic Filling at 6 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Fesoterodine: mean 7.84 versus 69.58 on control; difference -61.74 (95% CI -77.70 to -45.78), standardized effect d = -3.12; z-test p = <0.001.
  • Solifenacin: mean 24.06 versus 69.58 on control; difference -45.52 (95% CI -63.06 to -27.98), standardized effect d = -1.86; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Fesoterodine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Solifenacin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists eight secondary outcomes, covering additional measures of colonic emptying, transit, filling, gastric emptying, stool frequency and bowel-movement characteristics. Numerical results are posted for three: proximal colonic emptying time, colonic transit at 48 hours and colonic filling at 6 hours. Numerical results for the other listed secondary outcomes are not reported in the registry record.

The posted secondary estimates show a varied pattern rather than a uniform shift across measures. The unadjusted re-calculations indicate longer proximal colonic emptying time for both active groups relative to placebo, while the 48-hour transit comparisons are less clearly separated from placebo in their intervals. Colonic filling at 6 hours shows substantially lower posted means in both active groups than in placebo, with re-calculated intervals that do not include zero. These findings describe different aspects and time points of gastrointestinal transit; they should not be collapsed into one overall treatment effect.

The primary endpoint is the 24-hour geometric centre, a weighted distribution measure. Secondary measures can add context because they assess other features, but they do not replace the primary measure or automatically explain it. Differences between outcomes may reflect that they measure different processes, use different scales or capture different assessment times. The registry does not report a prespecified hierarchy among the secondary outcomes.

All posted secondary re-calculations are unadjusted. As a general statistical concern, examining multiple outcomes can increase the likelihood of apparently notable results arising by chance, particularly when no multiplicity adjustment is reported. The registry record does not describe a correction or confirmatory strategy for these outcomes. Consequently, secondary findings carry less weight as evidence of a reproducible effect than results from an analysis plan that specified how multiple comparisons would be handled. They are best read as descriptive and exploratory alongside the primary result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Proximal Colonic Emptying Time
• Colonic Transit at 48 Hours
• Colonic Filling at 6 Hours
• Time to Gastric Emptying
• Mean Number of Stools Per Day
• Mean Score of Stool Consistency Per Day
• Average Score of Ease of Passage During Defecation Per Day
• Mean Proportion of Bowel Movements With Satisfaction Per Day

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous, and the registry reports group means and standard deviations. A mean describes the centre of the observed values in a group; a standard deviation describes their spread around that mean. These summaries are useful for understanding the observed distribution, but comparisons also need to account for uncertainty in the estimated group difference. The registry’s posted results include both unadjusted re-calculations based on those summaries and a sponsor-reported ANCOVA comparison.

What does a mean difference represent?

A mean difference expresses the average value in one group relative to another. In the placebo re-calculations, the comparator is placebo and the estimates are -0.53 for fesoterodine and -0.6 for solifenacin. The negative signs indicate that the active-group means are lower than the placebo mean for this endpoint. Since GC24 assigns lower weights to more proximal locations, the sign describes the direction of the score difference, not a judgment about whether that difference is clinically beneficial.

The re-calculations use posted arm-level means and standard deviations and are unadjusted. They are not the sponsor’s ANCOVA analysis and do not incorporate any covariate adjustment. The registry record reports no p-value for the sponsor’s ANCOVA. Its least-squares mean difference is an adjusted estimate for the comparison between the two active groups, whereas the re-calculated estimates compare each active group with placebo. The values should therefore be interpreted as different analyses of different contrasts.

What does a confidence interval convey?

As a general statistical explanation, a confidence interval describes the uncertainty around an estimated contrast under the assumptions of the analysis. It gives a range of values compatible with the observed data and method; it does not assign a probability to the specific true value being inside the already calculated interval. For the placebo comparisons, the posted intervals include zero. That means a zero difference is among the values compatible with those re-calculations, while the endpoints also indicate the range of nonzero differences that remain compatible with the estimates. The sponsor’s 95% interval for the adjusted active-treatment comparison also includes zero.

How should p-values be read?

As a general statistical explanation, a p-value measures how unusual data at least as discordant with a specified null model would be, if that model and the analysis assumptions were true. It is not the probability that a treatment has no effect, and it does not measure clinical importance. The re-calculated p-values are unadjusted: 0.127 for fesoterodine versus placebo and 0.068 for solifenacin versus placebo. The posted registry result does not include a p-value for its ANCOVA. The record does not report whether any other inferential decision rule was used.

Because the calculations are unadjusted, each p-value is interpreted without accounting for the number of outcomes or comparisons. When many comparisons are examined, the chance of encountering a small p-value by chance can increase. The registry record does not report an adjustment strategy, so the secondary results should be read as exploratory descriptions rather than as a set of multiplicity-controlled tests.

What is ANCOVA?

As a general statistical explanation, analysis of covariance estimates a group contrast while adjusting for specified covariates. The registry identifies the reported analysis as ANCOVA and gives a least-squares mean difference for fesoterodine versus solifenacin. The covariates, model specification, assumptions, and handling of missing observations for this reported analysis are not reported in the registry record. It is therefore possible to describe the posted adjusted estimate and interval, but not to reconstruct the model or determine the influence of particular covariates.

What do the population and imputation statements mean?

The registry says the intent-to-treat population included all randomized subjects and that missing data were imputed by the overall mean. As a general statistical explanation, an intent-to-treat approach aims to analyze participants according to their randomized assignment. Overall-mean imputation replaces missing values with a common value calculated across the analysis population; it can reduce apparent variability and may affect comparisons depending on how much data are missing and why. The number and pattern of missing values, and the details of the overall mean used, are not reported in the registry record. Those omissions make it difficult to assess the sensitivity of the result to the imputation method.

The posted summaries also reflect unequal group sizes, particularly the placebo group’s 12 participants compared with 25 for fesoterodine and 23 for solifenacin. General statistical reasoning says estimates from smaller groups tend to be less precise when other factors are similar. The posted standard deviations and intervals give some information about observed spread and uncertainty, but they do not resolve possible imprecision or limitations arising from missing data, model choices or the small study population.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate an estimated difference. A point estimate alone does not show that uncertainty; the interval around it is essential. For fesoterodine versus placebo, the re-calculated mean difference is -0.53 and the interval extends from -1.211 to 0.150. For solifenacin versus placebo, the estimate is -0.6 and the interval extends from -1.245 to 0.045. Each interval includes zero, so the posted data do not rule out no mean difference under these unadjusted calculations.

The range of values within an interval also shows that estimates are not perfectly precise. The interval endpoints allow effects in directions on either side of zero, with the exact range differing by comparison. A confidence interval is not a statement that every value inside it is equally plausible, nor does it address whether a difference would matter clinically. The registry does not report a GC24 threshold for clinical importance, so statistical uncertainty cannot be translated into a clinical judgment from this record alone.

The sponsor’s adjusted active-treatment estimate is 0.051, with a 95% confidence interval from -0.334 to 0.436. This is a separate contrast from the placebo re-calculations. Its interval also includes zero. The registry record does not report a p-value for the ANCOVA estimate, and its covariate specifications are not reported in the registry record.

Precision should also be considered in the context of the posted group sizes and standard deviations. The placebo group had 12 participants for the primary endpoint, compared with 25 for fesoterodine and 23 for solifenacin. The standard deviations differ across arms, so group size alone does not fully describe uncertainty. The intervals provide a direct summary of uncertainty for the re-calculated contrasts, while the registry does not give arm-specific confidence intervals for the means. The trial’s phase 1 setting and healthy-subject population further limit generalization, rather than changing the mathematical meaning of the intervals.

12. 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 sample-size illustrations describe hypothetical planning needs based on fractions of the observed re-calculated effect. For these continuous outcomes, the figures are participants per arm, not total participants and not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The figures are not observed power.

The 80% power column means the number of participants per arm under those assumptions for a planning scenario designed to have an 80% chance of detecting the specified effect, if the assumptions and effect size used for planning hold. The 90% power column expresses the corresponding planning target for a 90% chance. These are design illustrations, not findings about the probability that the trial detected an effect or about the truth of a treatment difference.

Each comparison has its own observed effect and variability, so its planning figures differ. For example, the placebo comparisons for the primary endpoint use different observed mean differences, and the resulting planning illustrations are not interchangeable. Planning for 100% of the observed effect uses the full observed estimate; planning for 75% or 50% of the observed effect assumes a smaller target. Smaller effects need more participants to detect under otherwise identical assumptions, which is why the displayed participant requirements rise as the target fraction decreases.

The registry’s original design assumptions and sample-size justification are not reported in the registry record. These calculations cannot establish what the investigators planned or whether the completed study met its original objectives. They are retrospective illustrations based on the observed summaries and should be interpreted as planning aids only.

13. 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 = -0.530; pooled standard deviation σ = 0.879.
2. n = 2 × (1.96 + 0.842)² × 0.879² / -0.530² = 43.1, rounded up to 44 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 <- -0.53                      # observed difference in means
sigma <- 0.878513744912395                     # 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(832650)
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 = 44 (80% power), 58 (90% power)
 75% of observed effect: n per arm = 77 (80% power), 103 (90% power)
 50% of observed effect: n per arm = 173 (80% power), 231 (90% power)
power.t.test: 44.1 
Simulated power at n = 44 per arm: 0.796 (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.

14. Analyses Reported by the Sponsor

The registry reports an ANCOVA for the comparison between fesoterodine and solifenacin. Its least-squares mean difference is 0.051, with a 95% confidence interval from -0.334 to 0.436. The registry does not report a p-value for this analysis. The interval includes zero and describes uncertainty around this adjusted active-treatment contrast.

The re-calculated comparisons are different: they compare each active group with placebo using the posted arm means and standard deviations, without adjustment. They yield mean differences of -0.53 for fesoterodine versus placebo and -0.6 for solifenacin versus placebo. Their p-values are unadjusted. Because these calculations differ in both comparator and method from the sponsor’s analysis, the estimates should not be treated as competing versions of the same result.

No discrepancy is flagged between the posted results and the re-calculations. The sponsor analysis remains the registry’s reported adjusted analysis for the active-treatment comparison, while the re-calculations provide simple, unadjusted comparisons against placebo. The model covariates and other ANCOVA details are not reported in the registry record, so the adjusted estimate cannot be reconstructed from the posted information alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and eight secondary outcomes. The results include multiple group comparisons for several continuous measures. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a plan for controlling the overall chance of false-positive findings across outcomes and comparisons. The unadjusted p-values therefore address individual comparisons and do not account for the broader set of tests.

As a general statistical explanation, multiplicity matters because making many inferences creates more opportunities for a small p-value to occur by chance, even when no real differences exist. Adjustment procedures or prespecified testing sequences can address that issue, but the record does not identify one. This is especially relevant to secondary results: their pattern may be useful for describing the study, but isolated unadjusted findings should not be treated as definitive confirmation.

The primary outcome population is described as intent to treat, including all randomized subjects, with missing data imputed by the overall mean. The registry record does not report the amount of missing data, the number imputed, reasons for missingness, or sensitivity analyses using alternative approaches. As a general statistical concern, replacing missing observations with an overall mean can alter estimated group variability and may influence the estimated contrast. The direction and size of any such influence cannot be determined without further information.

The registry also does not report a detailed statistical analysis plan, the planned covariates for ANCOVA, or the original sample-size justification. These missing details limit the ability to assess whether the posted analyses followed a prespecified plan and how robust the estimates are to alternative choices. These are reporting limitations; they do not establish that the analyses were conducted incorrectly.

16. 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

For serious adverse events, the registry reports zero affected participants in each arm: 0 of 25 at risk for fesoterodine, 0 of 12 for placebo and 0 of 22 for solifenacin. These are participant counts, not event rates calculated from another denominator. The registry lists no serious adverse-event terms.

A zero count in this study means that no serious adverse events were recorded among the participants at risk in the posted data. It does not demonstrate that serious events cannot occur, and the small group sizes limit what can be inferred about uncommon events. The deaths fields are not populated with a numerical value, so deaths are not reported in the registry record; they should not be interpreted as a confirmed count of zero.

The registry also reports other adverse events affecting 22 of 25 participants in the fesoterodine group, 6 of 12 in placebo and 15 of 22 in solifenacin. Those figures are distinct from the serious-event counts, and the record does not provide event terms or further context for interpreting them. Safety counts are descriptive and do not establish a comparative safety conclusion.

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

The posted results describe measurements from a randomized, triple-masked, parallel-group phase 1 study of healthy female subjects. For the primary 24-hour geometric-centre outcome, the mean values were 1.98 for fesoterodine, 2.51 for placebo and 1.91 for solifenacin. The simple re-calculations comparing active arms with placebo have intervals that include zero. The sponsor’s adjusted comparison between the two active groups also has a 95% interval that includes zero.

Those estimates describe the data and their uncertainty; they do not establish that either treatment works or does not work. The record does not report a threshold for a clinically important difference in GC24, so the size of the observed contrasts cannot be translated into a clinical judgment using this endpoint alone. The geometric centre is a weighted distribution score, not a direct measure of symptoms or patient benefit.

The secondary outcomes offer additional descriptive information, but their unadjusted comparisons and the absence of a reported multiplicity strategy limit the weight that should be placed on individual findings. Several listed secondary outcomes have no numerical results reported in the registry record. The amount of missing primary outcome data and the details of the imputation are also not reported, which restricts assessment of sensitivity to missing-data assumptions.

The study’s healthy-subject population and phase 1 designation are important context. These data do not directly answer questions about clinical outcomes in a patient population. The registry record also does not provide detailed protocol or analysis-plan information needed to evaluate all aspects of conduct and inference. Conclusions should stay within the narrow scope of the recorded measures, groups, analysis methods and uncertainty.

18. Why This Trial Matters Statistically

This trial is statistically useful as an example of why a study’s stated question, posted outcome and reported analysis need to be distinguished. The brief summary names the comparison of fesoterodine with solifenacin, while the sponsor-reported ANCOVA is that active-treatment comparison and the simple re-calculations use placebo as the comparator. These contrasts answer different questions and cannot be substituted for one another.

It also illustrates why a point estimate should be read alongside its interval. The primary placebo comparisons have negative estimates, but their intervals include zero; the adjusted active-treatment estimate is close to zero and its 95% interval also includes zero. Looking only at group means or the direction of an estimate would omit uncertainty. Looking only at a p-value would omit the range of compatible differences and any question of clinical importance.

The secondary outcomes demonstrate another statistical issue: multiple unadjusted comparisons are harder to interpret as a unified body of evidence when no adjustment or prespecified hierarchy is reported. A pattern across measures can be informative, but it does not automatically confirm the primary result. The record’s imputation statement also highlights why missing-data methods and their sensitivity matter, even when a population is labeled intent to treat.

Finally, the sample-size illustrations are retrospective planning calculations based on observed effects, not proof of the original design’s adequacy or the likelihood that an effect was detected. Together, these features make the registry record a useful case for careful reading of estimands, uncertainty, multiplicity, missingness and the limits of generalization.

19. 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 primary endpoint is a constructed geometric-centre score, and the registry does not report a threshold for clinical importance. That limits interpretation of the magnitude of the differences beyond their direction and statistical uncertainty. The record also does not report patient-reported outcomes or explain how a change in GC24 relates to symptoms or functioning.

There are important reporting gaps in the analysis details. The overall-mean imputation method is named, but the quantity and pattern of missing data and any sensitivity analyses are not reported in the registry record. The covariates and model specification for the sponsor’s ANCOVA are also not reported. These gaps prevent independent reconstruction of the adjusted estimate and a fuller appraisal of assumptions.

The posted group sizes are unequal, with 12 participants in the placebo group for the primary endpoint and larger active groups. The study is phase 1 and enrolled healthy female subjects, which constrains the scope of inference. The registry status is terminated, but the reason for termination is not reported in the registry record. The original sample-size justification, allocation ratio and detailed protocol are not reported either.

Multiple secondary outcomes are listed, but numerical results are not posted for all of them, and the registry does not report a multiplicity strategy. The unadjusted secondary comparisons therefore have limited confirmatory value. The serious-event counts are descriptive, and the missing numerical death entries cannot be treated as zero counts. These limitations concern the completeness and interpretability of the posted record; they do not, by themselves, demonstrate bias or invalidate the reported estimates.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Multiple Dose Study To Investigate The Effects Of Fesoterodine And Solifenacin On Gastrointestinal Transit — NCT00832650.
• Registry record last updated 2010-12-24; status last verified 2010-12.
• Results first posted 2010-12-24.
• 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.

23. Record Summary

The registry record describes a randomized, triple-masked, parallel-group phase 1 study of fesoterodine, solifenacin and placebo in healthy female subjects, with enrollment of 60 and status recorded as terminated. Its primary outcome was colonic transit at 24 hours, measured as a weighted geometric centre of colonic counts and stool.

Primary group means were 1.98 for fesoterodine, 2.51 for placebo and 1.91 for solifenacin. Unadjusted re-calculations versus placebo have intervals that include zero. The sponsor-reported ANCOVA compares the active groups and gives a least-squares mean difference of 0.051 with a 95% confidence interval from -0.334 to 0.436.

The registry identifies an intent-to-treat population with overall-mean imputation, but missing-data details and several analysis-plan details are not reported in the registry record. Secondary results are unadjusted, and a multiplicity strategy is not reported. Serious adverse events were recorded for 0 participants in each arm; deaths are not reported in the registry record.