This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function (NCT00995072), a non-randomized na study. The primary outcome is Change in Female Sexual Function Index.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00995072 |
| Phase | NA |
| Condition | Hypertension, Female Sexual Dysfunction |
| Allocation | Non-Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | East Coast Institute for Research |
| Results posted | Yes |
2. Clinical Question
Population
Women studied in the context of hypertension and female sexual dysfunction. The registry record does not report further participant characteristics or the number analyzed for the primary outcome.
Intervention
Nebivolol 5 mg daily for 12 weeks, as one of the treatment periods in the crossover sequence.
Comparator
Metoprolol succinate 100 mg daily for 12 weeks, as the other treatment period. The treatment sequence varied between the two arms, but allocation was non-randomized.
Primary question
How does change in Female Sexual Function Index score compare across treatment periods with nebivolol and metoprolol succinate? The record defines this outcome but does not report the comparative result.
The study addresses a tolerability question raised in its summary: sexual side effects associated with beta-blockers may affect their use. The investigators describe nebivolol as a newer beta-blocker and set out to compare sexual function during its use with sexual function during metoprolol succinate use. That rationale is not itself evidence that either medicine improves or worsens sexual function.
The primary endpoint is change in the Female Sexual Function Index, a self-reported measure. The record states that the scale ranges from 2 to 36 and that higher scores indicate higher sexual function. Its stated timeframe is baseline and 12 weeks. As the study uses a crossover structure, participants receive both medicines in different periods, with a washout before switching. This makes the within-participant comparison central to the clinical question, while the non-randomized allocation means the treatment sequences are not described as randomly assigned.
No numerical change scores, group means, standard deviations, confidence intervals, or statistical tests for the primary comparison are reported in the registry record. The clinical question can therefore be described, but the direction, size, and precision of any observed comparison cannot be established from this record.
3. Trial Design
The registry record identifies a completed, non-randomized, quadruple-masked crossover study. Enrollment is listed as 29. The study start is recorded as 2009-10 and primary completion as 2013-04. The record names hypertension and female sexual dysfunction as conditions. It does not identify a phase beyond “NA.”
Both sequences include nebivolol and metoprolol succinate. In Arm A, participants received nebivolol 5 mg daily for 12 weeks, followed by metoprolol succinate 100 mg daily for 12 weeks. A two week washout without medication occurred before the switch. In Arm B, the order was reversed: metoprolol succinate 100 mg daily for 12 weeks, then nebivolol 5 mg daily for 12 weeks, with a two week washout before switching to nebivolol.
A crossover design allows each participant to receive both treatments, so comparisons can use measurements from both treatment periods within the same participant. This can account for stable participant characteristics in a within-person comparison. It also makes the sequence and timing of measurements important. Changes over time, effects that persist after a treatment period, and the washout interval can all matter when interpreting a crossover comparison. The registry record gives the treatment order and washout but does not report analyses of period or carryover effects.
Allocation is explicitly identified as non-randomized. Thus, the two sequences should not be treated as randomly assigned comparison groups. Quadruple masking is recorded, but the record does not specify which roles were masked or how masking was maintained. Further details about recruitment, eligibility criteria, adherence, and protocol deviations are not reported in the registry record. No inferential analysis results for the primary endpoint are reported, so the recorded design alone cannot establish the size or precision of a treatment comparison.
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: 4 subjects were randomized and dropped from the study prior to taking the study medication
Overall Study
| Stage | Nebivolol 5 mg Daily First, Then Metoprolol Succinate 100 mg | Metoprolol Succinate 100 mg First, Then Nebivolol 5 mg Daily |
|---|---|---|
| STARTED | 10 | 15 |
| COMPLETED | 9 | 12 |
| NOT COMPLETED | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: The number of participants analyzed for the measure are participants that had data available for both of the study periods.
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.
| Characteristic | Unit | Nebivolol 5 mg Daily First, Then Metoprolol Succinate 100 mg | Metoprolol Succinate 100 mg First, Then Nebivolol 5 mg Daily | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 12 | 21 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 9 | 17 |
| Age, Categorical: >=65 years | Participants | 1 | 3 | 4 |
| Sex: Female, Male: Female | Participants | 9 | 12 | 21 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | Participants | 9 | 12 | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Female Sexual Function Index, measured over Baseline, 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in Female Sexual Function Index score. The registry record describes the index as a self-reported instrument used to detect female sexual function. It gives a scale range from 2 to 36 and states that higher scores indicate higher sexual function. The timeframe is baseline and 12 weeks.
A change score expresses how a participant's measured value differs between a starting assessment and a later assessment. For a continuous outcome, a group mean change can describe the average change among participants included in the analysis. The standard deviation describes how spread out individual measurements are around that group mean; it is not the same as the uncertainty in the estimated mean.
A self-reported instrument can capture participants’ own assessments of function, which is relevant to the question posed in this study. Interpretation depends on how the questionnaire was administered and scored, who completed it, and which observations were included. The registry record does not report those operational details beyond its brief description of the scale and the stated timeframe.
The record says that participants analyzed for this measure were those with data available for both study periods. It does not give the number analyzed or the mean change and standard deviation for either treatment. Nor does it report a comparative estimate, confidence interval, or test result. The endpoint definition therefore clarifies what the study intended to measure, but it does not establish what the measured changes were.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a planned comparison of female sexual function during two treatment periods, but it does not report numerical results for the primary outcome. In particular, it gives no treatment-period means, mean changes, standard deviations, treatment contrast, confidence interval, or statistical test. Consequently, the direction and magnitude of the observed comparison and its statistical precision are not available from the record.
The primary outcome is continuous, and the record identifies the mean and standard deviation as its summary format. In general, a mean describes the central value of a group’s measurements, while a standard deviation describes their spread. Those summaries alone would not identify the uncertainty around a treatment contrast; uncertainty is commonly conveyed with a confidence interval or a statistical test. No such inferential results are listed in the registry record.
The crossover structure matters to interpretation. Each sequence receives both medicines, so an appropriate comparison would need to account for the paired nature of measurements rather than treating all observations as independent. General considerations in crossover studies include period effects, changes over time, and possible persistence of treatment effects across periods. The registry record does not state whether or how such factors were assessed. The washout is described as two weeks, but its adequacy for addressing carryover cannot be judged from the registry information alone.
Non-randomized allocation also limits what can be inferred from differences between the sequences. The record does not describe random assignment, and sequence membership could be associated with participant characteristics or other factors. Masking is recorded as quadruple, but the masked roles and procedures are not described. Neither masking nor crossover design removes all possible sources of bias.
The registry lists enrollment of 29, but that is not the number reported as analyzed for the primary endpoint. The outcome description specifies that analyzed participants had data available for both study periods; the actual number meeting that condition is not reported. The registry also does not report how missing measurements were handled or whether participants were excluded for other reasons.
Adverse-event fields list zero participants at risk and zero affected for each of the two treatment groups. Because the fields also list zero participants at risk, those entries do not establish that no events occurred among a defined group of exposed participants. They should not be read as a substantive safety comparison.
Without outcome estimates and their uncertainty, no conclusion about the comparative result can be drawn from this registry record. The design and endpoint describe the question under study, not the answer. Any planning illustrations based on an observed effect are not observed power and cannot substitute for reported outcome estimates or a documented statistical analysis.
9. Statistical Methods Explained
What does a mean change describe?
For a continuous measure such as the Female Sexual Function Index, a mean change summarizes the average difference between measurements at the relevant assessment points among participants included in the calculation. It is a group-level summary: individual participants may have changes above or below that average. The registry record identifies mean and standard deviation as the summary measures for the primary outcome, but it does not report their values.
A standard deviation describes variation among individual scores. It is not the uncertainty of the mean itself and is not a measure of the treatment contrast. To understand the precision of a comparison, readers generally need an estimate of the contrast together with an uncertainty measure, such as a confidence interval. A confidence interval describes a range of values compatible with the data under the statistical model and its assumptions. It does not show the probability that the true effect lies in that particular interval. No confidence interval or comparative estimate is reported in the registry record.
Why does the crossover structure matter?
In a crossover study, participants receive more than one treatment in successive periods. Measurements from the same participant are related; they should not automatically be treated as if they came from independent people. A within-participant analysis can use the pairing of measurements and account for stable characteristics shared by that participant across periods. The registry record describes two treatment sequences, each containing both nebivolol and metoprolol succinate.
Time and order can also influence measurements. A period effect is a change associated with when a measurement is made, rather than solely with the treatment being taken. Carryover refers to a treatment effect that persists into a later period. In general, a washout interval is intended to reduce the influence of prior treatment before the next period. The record specifies a two week washout between treatments, but it does not report an analysis of period effects or carryover, or information that would establish whether the washout was sufficient.
What does non-randomized allocation imply?
Random allocation is one way to make treatment groups comparable in expectation, including on characteristics that are not measured. This study is identified as non-randomized, so that protection cannot be assumed. The treatment sequences may differ for reasons related to allocation or participant characteristics. In a crossover design, each participant receives both medicines, but non-random assignment of sequence can still matter, particularly if order, time, or carryover influences outcomes. The registry record does not describe how participants were assigned to sequence or whether analyses adjusted for any measured differences.
Quadruple masking is recorded, but the registry does not identify the roles that were masked or give procedural details. Masking can generally reduce the influence of expectations on treatment delivery, assessment, or reporting, depending on who is masked and how. The label alone does not establish which potential biases were addressed.
What can the planning assumptions tell readers?
The record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not estimates of the study’s observed power. The record does not provide the numerical planning outputs in the outcome information, nor does it report the study’s own sample-size justification. A planning calculation based on an observed effect also depends on the estimated effect used as its starting point; it cannot replace reporting the effect estimate and its uncertainty.
General sample-size planning asks how much information a future study might need to detect a specified effect under stated assumptions. Its result depends on those assumptions, including the analysis model and allocation. It does not show whether the current study’s observed result is reliable, and it is not a substitute for the actual analysis. The registry record does not report an interim analysis plan or a detailed statistical analysis plan.
What is not available for evaluating the analysis?
The primary endpoint description says the analyzed population consists of participants with data available for both study periods. This indicates a requirement for observations from both periods for the stated measure, but the record does not give the number analyzed. It also does not describe imputation, sensitivity analyses, exclusions, adherence handling, or a model for the paired observations. The registry lists a secondary outcome, Change in Sexual Functioning Questionnaire Score, but does not provide its results. It does not list inferential analysis results for the primary outcome.
Multiplicity arises when several outcomes, time points, or comparisons are tested. Testing multiple hypotheses can increase the chance of finding an apparently notable result by chance if no adjustment or prespecified testing strategy is used. The record identifies a primary outcome and a secondary outcome, but it does not report a multiplicity strategy or the statistical analysis plan. Therefore, no claim can be made about whether multiplicity was addressed. Without effect estimates, uncertainty measures, and analysis details, the statistical evidence for the treatment comparison cannot be assessed from the registry record.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| Nebivolol 5 mg Daily | 15 | 1.240 | 9.183 | -3.845 to 6.325 |
| Metoprolol Succinate 100 mg Daily | 15 | 1.420 | 5.262 | -1.494 to 4.334 |
R code and output
arm <- c("Nebivolol 5 mg Daily", "Metoprolol Succinate 100 mg Daily")
n <- c(15, 15)
m <- c(1.24, 1.42)
sp <- c(9.183, 5.262)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM Nebivolol 5 mg Daily 15 1.240 9.183 -3.845 6.325
CARM Metoprolol Succinate 100 mg Daily 15 1.420 5.262 -1.494 4.33411. Multiplicity, Missing Data and Analysis Populations
The registry record identifies the Female Sexual Function Index change as the primary outcome and Change in Sexual Functioning Questionnaire Score as a secondary outcome. It does not report a prespecified testing hierarchy, an adjustment for multiple comparisons, or a broader multiplicity plan. In general, multiplicity can arise when investigators examine more than one outcome, time point, subgroup, or treatment contrast. If multiple tests are considered without an appropriate strategy, the chance of at least one apparently unusual result can increase. The record does not allow assessment of whether this issue was addressed in the study analysis.
For the primary measure, the record defines the analyzed participants as those with data available for both study periods. This suggests that the stated analysis requires data from both periods, but the number meeting that requirement is not reported. The enrollment figure should not be mistaken for the analyzed sample for this endpoint. The record does not describe how missing observations were handled, whether participants with incomplete data were excluded from other analyses, or whether sensitivity analyses were conducted.
The record also does not report a detailed analysis population, such as whether analyses followed assigned sequence or depended on treatment received. Since allocation was non-randomized, the treatment sequence and analysis population would be relevant to interpretation. Details about adherence, withdrawal, and protocol deviations are not reported in the registry record.
No statistical analysis plan, interim analysis procedures, or missing-data assumptions are reported. These omissions do not establish that such procedures were absent; they mean that they cannot be evaluated from the registry record. Without participant flow, outcome estimates, and the relevant analysis details, the extent to which missingness or multiple testing could affect interpretation is unknown.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was designed to compare female sexual function across periods of nebivolol and metoprolol succinate use. It describes a crossover sequence, doses, treatment durations, washout, and the primary measure. Those details clarify the question and the structure of the comparison, but they are not outcome findings.
No numerical primary-outcome results are reported. There is no reported mean change for either medicine, no comparative effect estimate, and no confidence interval or test result. It is therefore not possible to determine from this record whether scores changed, how the treatment periods compared, or how precisely any difference was estimated. The same limitation applies to the named secondary outcome, for which results are not reported.
The scale description gives context for interpreting a score if results are available: it ranges from 2 to 36, with higher scores indicating higher sexual function. It does not establish a clinically important difference, and the registry record does not state a threshold for interpreting change. A score’s meaning also depends on the observed data and the analysis population, neither of which is reported for the primary comparison.
The study’s completed status does not mean that the registry record contains a complete account of its results. Likewise, the enrollment figure does not establish how many participants contributed data to the primary analysis. The record’s definition requires data for both study periods but does not report the analyzed count.
The adverse-event entries list zero at risk and zero affected in both treatment groups. With no participants listed at risk, these entries cannot be taken as evidence that no adverse events occurred in an exposed population. They do not support a comparative safety conclusion.
Overall, the record documents a clinical question and a study design, but not the numerical results needed to evaluate the observed treatment comparison. It neither establishes benefit nor establishes lack of benefit. Any interpretation beyond the design and endpoint description would require outcome estimates and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it combines a crossover structure with non-randomized sequence allocation. Crossover designs can use within-participant comparisons, which may reduce the influence of stable differences between participants. At the same time, the timing and order of treatment periods become important. Changes over time and effects persisting after a treatment period can complicate interpretation. The record describes a washout but does not report how period or carryover effects were handled analytically.
The non-randomized allocation is important because the treatment sequences cannot be assumed comparable on the basis of random assignment. Even when participants receive both medicines, sequence-related differences can matter if time, order, or residual treatment effects influence the outcome. Masking is recorded as quadruple, but the masked roles and procedures are not described. These details shape how confidently potential sources of bias can be assessed.
The primary outcome is self-reported and continuous. Its scale direction is defined, but the registry record does not give the mean changes, variability, or comparative estimate. This illustrates a basic distinction in clinical-trial interpretation: a clearly defined endpoint and a completed study are not substitutes for transparent outcome reporting. Without an estimate and its precision, readers cannot judge the magnitude or uncertainty of the comparison.
The population analyzed is also consequential. The record says participants needed data from both study periods for the primary measure but does not report the number who met that condition or how missing data were handled. Enrollment alone cannot answer those questions. Finally, the presence of a primary and a secondary outcome raises questions about multiplicity and prespecification, but no analysis plan is reported. These limitations make the registry record useful for understanding the study question and design, while leaving the statistical result unevaluable.
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 registry record does not report the numerical results for the primary endpoint or the secondary outcome. It gives no treatment-specific means, standard deviations, comparative estimate, confidence interval, or test result. This prevents evaluation of the direction, magnitude, and precision of the comparison. The recorded outcome definition and study completion status do not fill that gap.
Although enrollment is listed as 29, the number analyzed for the primary outcome is not reported. The endpoint description restricts the analyzed population to participants with data available for both study periods, but the record does not describe missing-data handling, participant flow, or sensitivity analyses. It also does not report adherence, treatment discontinuations, or protocol deviations.
Non-randomized allocation limits interpretation of comparisons between treatment sequences. The record does not explain how sequence assignment occurred or whether baseline differences were assessed or adjusted for. A crossover design also requires consideration of order, period, and possible carryover effects. The registry record describes the two week washout but does not report whether these effects were assessed or how they were incorporated into an analysis.
Quadruple masking is recorded without identifying which roles were masked or describing the procedures. The record does not include a detailed statistical analysis plan, a multiplicity strategy, or interim analysis information. Such details are not reported in the registry record, so their presence or absence in the conduct of the study cannot be inferred.
Finally, the adverse-event fields list zero participants at risk in each treatment group as well as zero affected. Those entries do not establish a safety profile for participants exposed to treatment. Taken together, the available record supports description of the clinical question and design, but not a numerical assessment of efficacy or safety comparisons.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function — NCT00995072.
- Registry record last updated 2019-03-29; status last verified 2019-03.
- Results first posted 2019-03-29.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed, non-randomized, quadruple-masked crossover study with enrollment of 29. It compares treatment periods with nebivolol 5 mg daily and metoprolol succinate 100 mg daily; each period lasted 12 weeks, with a two week washout before switching. The primary outcome is change in Female Sexual Function Index score, measured at baseline and 12 weeks. The scale ranges from 2 to 36, and higher scores indicate higher sexual function.
The registry record states that participants analyzed for the primary measure had data available for both study periods, but it does not report the number analyzed or numerical outcome results. It also does not report a comparative estimate, confidence interval, statistical test, missing-data method, or detailed analysis plan. Consequently, the record describes the study question and design but does not establish the observed treatment comparison or its precision.