Study to Evaluate Effect of Nebivolol on Angina in Women With Microvascular Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Effect of Nebivolol on Angina in Women With Microvascular Disease (NCT01665508), a na phase 4 study. The primary outcome is Seattle Angina Questionnaire Score.

2. Clinical Question

The clinical question is whether anginal stability, as assessed by the Seattle Angina Questionnaire, differs between baseline and follow-up after nebivolol treatment in women with microvascular angina. Because participants were assessed over time without a separate control group, the design can describe within-group change, but it cannot by itself distinguish a treatment-associated change from changes that might have occurred for other reasons.

The study summary also proposes examining exercise capacity, resource utilization and measures of artery function. Listed secondary outcomes include peak VO2 measured by cardiopulmonary exercise testing, a resource utilization questionnaire, SF36, exercise duration, peak heart rate and peak O2 pulse. Their numerical results are not reported in the registry record.

3. Trial Design

This is a Phase 4, completed, single-group study of nebivolol in women with microvascular angina. The registry lists enrollment as 12 and describes the intervention as a drug. Allocation is listed as not applicable, and masking is listed as none. There is no randomized comparator group in the listed design.

Participants were assessed at baseline using the Seattle Angina Questionnaire, cardiopulmonary testing, resource utilization, metabolomics and vascular testing. The arm description says testing was repeated in the same group after 3 months of nebivolol treatment. This is a before-and-after structure: each participant’s follow-up assessment is intended to be interpreted in relation to that participant’s baseline, rather than as a comparison with a separate untreated group.

The registry reports that seven patients completed baseline and follow-up data for anginal stability. It does not explain why this outcome population is smaller than the listed enrollment, describe the availability of paired data for other outcomes, or give reasons for incomplete records. The study started in 2013-04, reached primary completion in 2015-05 and is listed as completed. Massachusetts General Hospital is the sponsor.

A single-group design can describe the observed course of measurements in the participants assessed, but it does not provide a concurrent control for separating treatment effects from other influences. The registry record does not report a detailed statistical analysis plan, a sample-size justification for the original study, interim analyses, or a more specific account of participant selection and follow-up procedures.

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

Analysis population for the primary outcome, as defined in the registry: 7 patients complete baseline and followup data reported below is anginal stability

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 Seattle Angina Questionnaire Score, measured over 3 months.

The primary endpoint is the Seattle Angina Questionnaire Score, with a timeframe of 3 months. The registry describes the SAQ as a validated, self-administered questionnaire used to assess angina stability and angina frequency in people with coronary artery disease. It describes five dimensions of health status: angina frequency, angina stability, disease-specific quality of life, physical limitations and treatment satisfaction. Each domain ranges from 0-100, with higher scores indicating better health status.

Although the primary outcome title refers broadly to the SAQ score, the registry identifies the reported data as anginal stability. That distinction matters: an anginal-stability domain score addresses the stability of symptoms, not every aspect of the questionnaire or overall health status. The stated unit is units on a scale, and the listed summary measure is a mean with standard deviation.

A mean gives the average score in the assessed group, while the standard deviation describes how spread out participant scores are around that mean. For a before-and-after question, the most informative result would ordinarily include the paired change and its uncertainty, alongside the scores at each time point. The numerical scores, change estimate and uncertainty are not reported in the registry record, so the magnitude and precision of any change cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists the primary outcome as a mean of a continuous measure, with standard deviation. A continuous score can take values across a scale rather than being limited to categories such as event versus no event. Reporting a mean describes the group’s average score; the standard deviation describes the spread of individual scores around that average. These summaries are descriptive and do not, by themselves, establish whether a change is statistically distinguishable from variation.

Why does the paired structure matter?

The same group was assessed at baseline and after 3 months. In a paired design, the two measurements from a participant are related, so an analysis of change should account for that within-person relationship. A comparison that treats baseline and follow-up measurements as if they came from unrelated groups would not reflect the stated design. The registry record does not say which statistical method was used for the primary outcome, so it is not possible to verify how the pairing was handled.

A mean change is often a useful summary for paired continuous measurements. Its interpretation depends on how the change is defined, and the score direction matters: the registry states that higher SAQ domain scores indicate better health status. A confidence interval around a change estimate would convey the range of values compatible with the observed data under the analysis assumptions. A narrow interval generally indicates greater precision than a wide interval. These are general statistical principles; the registry does not report a change estimate or confidence interval for this endpoint.

What can a significance test establish?

A significance test evaluates how compatible the observed data are with a specified statistical null hypothesis under the assumptions of the test. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. Interpretation should therefore consider the estimated change and its uncertainty, not a test result alone. The registry record does not report a p-value or identify the primary-outcome test, so no test-based conclusion can be drawn.

Precision is especially important when the available outcome population is described as seven patients with completed baseline and follow-up data. A limited set of paired observations can leave an estimate uncertain, but the degree of uncertainty depends on the observed scores and their variability. Neither is numerically. It would not be appropriate to infer a confidence interval, standard error or significance result from the enrollment figure alone.

How should the sample-size illustrations be read?

The sample-size assumptions describe planning illustrations based on a fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. For continuous outcomes, the illustrations are described in participants per arm. These are planning quantities, not observed power and not evidence that the original study was designed with those assumptions. The actual study is listed as single group, so an illustrative two-arm calculation does not describe its design. Numerical illustration results and the observed effect used for the calculation are not reported in the registry record.

A planning calculation asks how many participants might be required under chosen assumptions to detect a specified effect with a chosen probability, if those assumptions hold. It does not show that an effect was detected in the completed study. Nor does a calculation based on an observed effect establish that the effect is reproducible: an effect estimated in a small study may be uncertain. These are general considerations, and no numerical planning estimate can be evaluated from the information recorded.

Why does over-dispersion matter in general?

Over-dispersion means that observed variability exceeds what a statistical model assumes. If a model underestimates variability, its uncertainty estimates may be too small and its tests may be too optimistic. This issue is most relevant to outcomes analyzed with count or event models; the primary endpoint in this study is a continuous SAQ score. The registry does not report a model or diagnostics for over-dispersion, and there is no basis for saying that it affected this analysis.

More broadly, a sound statistical interpretation depends on transparent reporting of the analysis population, missing-data handling, outcome definition, effect estimate and uncertainty. The registry describes some of the design and outcome details but does not report those numerical primary-outcome results or a detailed analysis plan. General statistical principles can explain what such results would mean, but they cannot recover results that are absent from the record.

10. Multiplicity, Missing Data and Analysis Populations

The study lists secondary outcomes covering exercise capacity, exercise duration, peak heart rate, peak O2 pulse, resource utilization and SF36. The registry also lists seven outcome measures, but does not provide a detailed account of how many were tested, which were considered confirmatory, or how results across outcomes were interpreted. A multiplicity plan is not reported in the registry record.

Multiplicity arises when several outcomes or statistical tests are considered. The more results examined, the greater the chance that at least one may appear notable by chance if each is assessed separately. Methods for addressing this issue depend on whether outcomes are confirmatory or exploratory and on the analysis plan. Since no multiplicity approach is reported, the strength of any conclusions across outcomes cannot be assessed from the registry information.

For the primary outcome, the registry identifies seven patients with completed baseline and follow-up data for anginal stability. The listed enrollment is 12, but the record does not explain the difference between enrollment and the number with paired outcome data, give reasons for missing measurements, or describe any imputation or other missing-data method. It does not report whether the analysis used all available observations or a defined analysis population.

Incomplete follow-up can affect estimates if the participants with recorded outcomes differ systematically from those without them. The direction and size of any such influence cannot be determined from the registry record. The available information supports describing the stated paired-data population, but not assuming that it represents every enrolled participant or that missing data had no effect.

11. 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.

For the nebivolol group, the registry records zero serious adverse events among 12 at risk and zero other adverse events among 12 at risk. These are event counts as posted for this study. They do not establish that adverse events cannot occur, and they should not be interpreted as a precise estimate of safety beyond the participants and follow-up recorded in this trial.

The registry lists no serious adverse-event terms. The death figure is not reported in the registry record. The record also does not provide event definitions, details about how events were collected, or the duration and completeness of safety follow-up. Those omissions limit interpretation of what the zero counts cover.

With no separate control group, the event counts cannot be used to compare nebivolol with another treatment or with no treatment. They describe the registry’s reported experience in the single-group study; they do not establish whether an event was caused by the intervention.

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

The study is designed to describe changes in anginal stability after nebivolol treatment in women with microvascular angina. Its single-group, before-and-after structure is relevant to that descriptive question: the same group was assessed at baseline and after 3 months. The registry identifies seven patients with paired baseline and follow-up data for anginal stability.

The primary endpoint is a domain of the Seattle Angina Questionnaire, for which higher scores indicate better health status. But the numerical scores and change estimate are not reported in the registry record. Therefore, the posted information does not show whether anginal stability changed, how large any change was, or how precisely it was estimated. The registry’s description of the scale is not itself evidence of an outcome result.

The design also does not support attributing a possible before-and-after change solely to nebivolol. Without a separate control group, other influences over time cannot be separated from the intervention. This limitation remains even if a change were observed; the registry record does not report enough numerical information to evaluate one.

The safety figures report zero serious and zero other adverse events in the nebivolol group, with 12 at risk for each category. They describe recorded events in this study, rather than proving the absence of risk. The death count and important details about event ascertainment are not reported in the registry record.

Thus, the record supports a description of the study question, design, outcome definition, paired-data population and posted adverse-event counts. It does not support a numerical conclusion about the primary outcome, a causal claim about treatment, or a comparison with another treatment. The results needed to assess the magnitude and precision of an anginal-stability change are not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring change and establishing why change occurred. Repeating the SAQ in the same group can describe a before-and-after pattern, while the absence of a separate control group limits causal interpretation. Recognizing that distinction helps readers avoid treating a within-group comparison as if it were a randomized treatment comparison.

The registry also illustrates why outcome definitions and analyzed populations need to be read together. The primary outcome is titled as an SAQ score, while the population description identifies the reported data as anginal stability. The record states that seven patients completed baseline and follow-up data for that domain. These details clarify what the intended observation concerns, but they do not replace the actual scores and change estimate.

Precision is central to interpreting continuous outcomes. A mean and standard deviation can describe the score distribution, while a change estimate and confidence interval can describe the size and uncertainty of within-person change. Since the numerical endpoint results are not reported in the registry record, readers cannot assess those features or distinguish a potentially meaningful pattern from imprecise measurement.

Finally, the sample-size assumptions are described as planning illustrations using a two-arm framework, whereas the recorded trial is single group. Keeping planning calculations separate from the completed design prevents a hypothetical sample-size exercise from being mistaken for observed evidence or observed power. These design and reporting distinctions are important when interpreting small clinical studies and their limits.

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 main trial-specific limitation is that the registry record does not report the numerical primary-outcome results. Although it identifies the SAQ anginal-stability domain, its scale direction and the number of patients with paired data, it gives no baseline or follow-up mean, standard deviation, change estimate or confidence interval. The magnitude and precision of the primary outcome therefore cannot be assessed.

The single-group design has no concurrent control, so it cannot separate treatment-associated change from other influences over time. The record describes seven patients with completed baseline and follow-up anginal-stability data, compared with listed enrollment of 12, but does not report why the numbers differ or how incomplete outcome data were handled. Reasons for missing measurements and the analysis population are not reported in the registry record.

The registry lists secondary outcomes but does not report their numerical results or a multiplicity strategy. It does not provide a detailed primary statistical method, a sample-size justification for the original design, or information about interim analyses. The numerical sample-size illustrations and the effect value used for them are not reported in the registry record.

Safety interpretation is also limited by the lack of reported event definitions, ascertainment details and follow-up duration. The death count is not reported in the registry record. These gaps do not change the reported event counts, but they constrain what those counts can establish.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate Effect of Nebivolol on Angina in Women With Microvascular Disease — NCT01665508.
• Registry record last updated 2017-04-20; status last verified 2016-12.
• Results first posted 2017-04-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This completed Phase 4 study evaluated nebivolol in women with microvascular angina using a single-group, before-and-after design. The same group was assessed at baseline and after 3 months of treatment. Enrollment is listed as 12, and the registry identifies seven patients with completed baseline and follow-up data for anginal stability.

The primary endpoint is the Seattle Angina Questionnaire Score, with the reported data described as anginal stability. The numerical scores, change estimate and uncertainty are not reported in the registry record. Listed secondary outcomes include cardiopulmonary exercise measures, resource utilization and SF36, but their numerical results are not reported.

The nebivolol group has zero serious adverse events and zero other adverse events recorded among 12 at risk in each category. The death count is not reported in the registry record. The single-group design and incomplete reporting of outcome results limit conclusions about change and its cause.