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 An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Female-specific Angina Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041) (NCT00644332), a non-randomized phase 4 study. The primary outcome is Evaluate the Validity of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and Nitroglycerin (NTG) Consumption Before and Following Treatment With Ranolazine Assessed as Coefficient of Determination (R^2).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00644332 |
| Phase | Phase 4 |
| Condition | Chronic Angina |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 172 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Gilead Sciences |
| Results posted | Yes |
2. Clinical Question
Population
Women with chronic angina. The study enrolled 172 participants; its primary analysis population was narrower, including patients who took at least 1 dose of ranolazine and completed both baseline and postbaseline questionnaires.
Intervention
Ranolazine extended-release tablets. The study was open-label, and the registry describes ranolazine treatment as the context for assessing changes in symptoms and questionnaire responses.
Comparator
There was no separate randomized control group. The study compared the Women's Ischemia Symptom Questionnaire (WISQ) with the Seattle Angina Questionnaire (SAQ) on like or related measures, rather than comparing ranolazine with another treatment.
Primary question
Does the WISQ show validity in women with chronic angina, assessed through its relationship to patient-reported angina frequency, nitroglycerin consumption, and the Duke Activity Status Index (DASI) after ranolazine treatment? The registry specifies a regression-based coefficient of determination for this assessment, but the result is not reported in the registry record.
The study also set out to examine reliability and responsiveness, and to compare changes in WISQ and SAQ responses. Other listed outcomes include diary-based angina frequency and nitroglycerin use, DASI changes, and correlations between questionnaire changes and those measures. These aims concern how well a symptom questionnaire measures and tracks patient-reported experience. They do not constitute a randomized test of ranolazine against a control treatment.
3. Trial Design
This was a completed phase 4, open-label, multicenter study with nonrandomized allocation and a single-group model. The registry lists 172 participants with chronic angina and ranolazine as the intervention. The study began in 2007-11, and primary completion was 2011-01. Because participants were not randomized between treatment groups and no control arm is described, the design is not a like-for-like treatment comparison.
The study's focus was measurement: evaluating the validity, reliability, and responsiveness of the WISQ in women with chronic angina treated with ranolazine. Its stated background notes that evaluating angina and response to antianginal therapy can be difficult, and motivates a questionnaire developed specifically for women. The SAQ was included as a widely used comparison instrument. Listed secondary aims include comparisons of angina-frequency items, physical-limitation items, and other like items on the WISQ and SAQ, along with diary and DASI outcomes.
The primary analysis population is described as a modified intent-to-treat set: patients who took at least 1 dose of ranolazine and completed both baseline and postbaseline questionnaires. That definition means the primary analysis was not simply everyone enrolled. The number meeting the analysis-set definition is not reported in the registry record. The registry also does not report the treatment duration beyond the primary endpoint's Baseline to Week 4 timeframe, the dosage regimen, or details of visit scheduling.
Open-label, single-group evidence can describe questionnaire behavior and changes observed during treatment, but it cannot isolate a treatment effect from changes over time, expectations, or other influences. The absence of randomization and a control arm is therefore central to interpreting the study. The registry record does not report a statistical plan that would allow further characterization of design choices, such as an interim analysis or a sample-size justification.
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: In the 2-week qualifying phase, patients continued antianginal medications without changing dose or frequency and completed questionnaires to document angina symptoms, treatment and status. Patients who had average angina frequency of ≥ 2 attacks/week during this phase and met all enrollment criteria were enrolled in the open-label treatment phase.
Overall Study
| Stage | Ranolazine |
|---|---|
| STARTED | 171 |
| COMPLETED | 150 |
| NOT COMPLETED | 21 |
Reasons for not completing this period:
| Reason | Ranolazine |
|---|---|
| Adverse Event | 11 |
| Withdrawal by Subject | 6 |
| Completion Status Unknown | 2 |
| Did Not Meet Eligibility Requirements | 1 |
| Could Not Attend Scheduled Visits | 1 |
Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat Analysis Set, defined as all patients who took at least 1 dose of ranolazine and completed both baseline and postbaseline questionnaires. Partially missing questionnaire responses were imputed by the methods specified in the scoring instructions; completely missing responses were not imputed.
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 | Ranolazine |
|---|---|---|
| Participants analysed | 171 | |
| Age Continuous | years | 64.6 (SD 12.0) |
| Sex: Female, Male: Female | Participants | 171 |
| Sex: Female, Male: Male | Participants | 0 |
| Race/Ethnicity, Customized: Asian | participants | 3 |
| Race/Ethnicity, Customized: Black | participants | 20 |
| Race/Ethnicity, Customized: Caucasian | participants | 143 |
| Race/Ethnicity, Customized: Hispanic | participants | 5 |
| Region of Enrollment: United States | participants | 171 |
| Body Mass Index | kg/m^2 | 29.5 (SD 6.3) |
| Weight | kg | 76.7 (SD 17.6) |
6. Primary Endpoint
The registry lists the primary outcome as Evaluate the Validity of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and Nitroglycerin (NTG) Consumption Before and Following Treatment With Ranolazine Assessed as Coefficient of Determination (R^2), measured over Baseline to Week 4.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | coefficient of determination |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is a coefficient of determination, R^2, from a regression analysis intended to assess the validity of the WISQ. The registry describes the WISQ Total Score at 4 weeks as the outcome in a regression on 4-week angina frequency, 4-week nitroglycerin use, and DASI score at 4 weeks. Its stated timeframe is Baseline to Week 4. Although the endpoint description frames validity around changes before and following treatment, the specified regression uses the week-4 measures; the registry record does not explain how baseline change is incorporated into that model.
In general, R^2 describes how much of the variability in an outcome is accounted for by the fitted regression model. For a questionnaire-validation question, examining the relationship between questionnaire scores and measures related to symptoms or activity can provide evidence about whether the questionnaire behaves as expected. It is not, by itself, a direct measure of agreement, reliability, or treatment benefit. Interpretation depends on the model, the selected measures, and the quality and completeness of the data.
The registry record does not report the R^2 estimate, its uncertainty, or a p-value. It therefore does not establish from the posted primary result how closely WISQ scores were associated with the listed measures. The endpoint's intended role can be described, but its empirical result cannot be interpreted without that estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a measurement study, not a randomized comparison of ranolazine with another treatment. Its primary question concerns whether the WISQ is valid in women with chronic angina, using a regression-based association with angina frequency, nitroglycerin use, and DASI. The principal quantitative result needed to answer that question—the estimated R^2—is not reported in the registry record. No confidence interval or p-value for the primary endpoint is reported either. Consequently, the strength and precision of the reported primary relationship cannot be assessed from the registry record.
The endpoint description identifies WISQ Total Score at 4 weeks as the regression outcome and the three week-4 measures as predictors. The record labels the timeframe Baseline to Week 4, while the stated regression uses measurements at week 4. This distinction matters: an association among scores measured at the same time is not the same quantity as an association between changes from baseline. The registry record does not clarify whether the analysis also incorporated change scores or baseline values.
The study's secondary aims include comparison of WISQ and SAQ items, changes in diary-based angina frequency and nitroglycerin use, DASI change, and correlations between questionnaire changes and other measures. These aims could provide complementary evidence about measurement performance, but the registry record does not report numerical results for them. It also does not report results establishing the WISQ's reliability or responsiveness. The listed aims should therefore not be read as findings.
Enrollment was 172, but the defined primary analysis set required both a dose of ranolazine and completed baseline and postbaseline questionnaires. The number included in that analysis is not reported in the registry record. Without the analysis-set size and outcome estimates, readers cannot judge how much information contributed to the primary assessment or how precisely it was estimated.
The safety record lists 8 participants affected by serious adverse events among 171 at risk and 34 affected by other adverse events among 171 at risk. These are descriptive safety figures in a single-group study; they do not establish whether events were caused by ranolazine. Deaths are not reported in the registry record. The record lists several serious-event terms with percentages, but does not give enough information to treat those terms as a complete account of event frequency or to compare risks against a control group.
Overall, the registry record supports describing the study's purpose, design, analysis population definition, and some safety counts. It does not contain the primary efficacy-of-measurement estimate or the other outcome results needed to draw conclusions about the questionnaire's performance. No conclusion about a treatment effect can be drawn from the described design alone.
9. Statistical Methods Explained
The primary endpoint uses regression to examine the relationship between WISQ Total Score and measures expected to relate to angina symptoms and functional status. In general, regression describes how an outcome varies with one or more explanatory measures under a specified model. Here, the registry names angina frequency, nitroglycerin use, and DASI score at 4 weeks as predictors, and WISQ Total Score at 4 weeks as the outcome. The registry reports that the analysis result is expressed as R^2, the coefficient of determination.
What does R^2 describe?
In general, R^2 summarizes the proportion of variability in the modeled outcome accounted for by the fitted predictors. It is a measure of model fit for that outcome and model, not a measure of causation. A higher R^2 does not, on its own, show that a questionnaire is reliable, that it detects change well, or that treatment caused a change. The estimate is also specific to the included predictors, the population analyzed, and the model's assumptions. The R^2 value and any measure of its uncertainty are not reported in the registry record.
How does this relate to questionnaire validity?
In general, validity concerns whether an instrument measures the construct it is intended to measure. One way to examine validity is to assess whether questionnaire scores relate to other measures in ways consistent with the instrument's intended meaning. The registry's selected measures—angina frequency, nitroglycerin consumption, and DASI—represent related patient-reported or activity information. Their association with WISQ scores could contribute evidence about validity, but the endpoint description alone does not establish the result. The registry does not report the expected direction or magnitude of association, or a criterion for judging the WISQ successful.
Reliability and responsiveness are distinct measurement properties. In general, reliability concerns consistency of measurement, while responsiveness concerns the ability to register change when the underlying state changes. The study's stated aims include both properties, but the registry record does not report the methods or estimates for assessing them. No particular test-retest procedure, reliability coefficient, or responsiveness criterion is described in the available record.
What does the study design allow?
The study is open-label and single-group, with nonrandomized allocation. These characteristics do not prevent evaluation of relationships among questionnaire and symptom measures, but they limit causal interpretation of change during treatment. In general, without a concurrent control group, observed change cannot be separated from time trends, expectations, changes in other care, or other influences. The design also does not support a randomized comparison between ranolazine and an alternative intervention.
The registry describes a modified intent-to-treat analysis set consisting of patients who took at least 1 dose of ranolazine and completed baseline and postbaseline questionnaires. This definition selects participants based partly on questionnaire completion. The number included in the primary analysis and the extent of missingness are not reported in the registry record. Those details would be useful for assessing how representative the analyzed group was of all enrolled participants.
For partially missing questionnaire responses, the registry says values were imputed by the methods specified in the scoring instructions. It does not identify those methods in the available description. How completely missing questionnaire responses were handled is not reported in the registry record. In general, imputation choices can affect estimates, particularly when the amount or pattern of missingness is related to participant characteristics or outcomes.
How should planning illustrations be understood?
The registry's sample-size assumptions describe a planning illustration computed from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These assumptions are not a description of the actual trial design, which was single-group and nonrandomized. The registry record does not report the sample-size justification for the trial, and the planning assumptions should not be interpreted as observed power. Numerical planning results are not reported in the registry record.
The record lists 10 outcome measures and 3 analyses, but does not report a multiplicity adjustment or a complete statistical analysis plan. In general, when multiple outcomes or analyses are examined, the chance of at least one apparently notable result can increase if each is interpreted without accounting for the set of tests. Whether adjustment is appropriate depends on the analysis objectives and prespecified hierarchy; those details are not reported in the registry record. Accordingly, no multiplicity strategy should be inferred.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures and 3 analyses. It does not report whether the primary endpoint had a prespecified testing hierarchy, whether secondary outcomes were treated as confirmatory or exploratory, or whether any adjustment was made for multiple testing. The statistical plan, including the approach to multiplicity, is not reported in the registry record. In general, examining multiple outcomes can increase the chance of finding an apparently notable result by chance; interpretation depends on how analyses were planned and how their results are used.
The primary analysis population is defined as patients who took at least 1 dose of ranolazine and completed both baseline and postbaseline questionnaires. This definition is not equivalent to including every enrolled participant regardless of questionnaire completion. The number who met the definition is not reported in the registry record, nor are the numbers excluded for each reason.
The registry states that partially missing questionnaire responses were imputed using methods specified in the scoring instructions. Those methods are not described in the registry record. The handling of completely missing responses is also not reported in the registry record. The record does not give the amount or pattern of missing data, or sensitivity analyses assessing whether results depended on the imputation approach.
In general, missing-data methods rely on assumptions about why measurements are absent. Different assumptions can lead to different estimates, especially if missingness is associated with symptoms or participant characteristics. Without details about missingness and the imputation procedure, readers cannot assess those assumptions or how strongly missing data may have influenced the primary and secondary analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ranolazine | 8 | 171 | 4.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ranolazine | 34 of 171 |
Most frequent serious adverse event terms
| Event term | Organ system | Ranolazine |
|---|---|---|
| Chest pain | General disorders | 3 of 171 |
| Acute coronary syndrome | Cardiac disorders | 1 of 171 |
| Angina unstable | Cardiac disorders | 1 of 171 |
| Cardiac failure congestive | Cardiac disorders | 1 of 171 |
| Non-cardiac chest pain | General disorders | 1 of 171 |
| Urinary tract infection | Infections and infestations | 1 of 171 |
| Contusion | Injury, poisoning and procedural complications | 1 of 171 |
| Fall | Injury, poisoning and procedural complications | 1 of 171 |
| Pubic rami fracture | Injury, poisoning and procedural complications | 1 of 171 |
| Dizziness | Nervous system disorders | 1 of 171 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ranolazine |
|---|---|---|
| Nausea | Gastrointestinal disorders | 22 of 171 |
| Dizziness | Nervous system disorders | 9 of 171 |
| Headache | Nervous system disorders | 9 of 171 |
Serious events with the highest arm-level rate: chest pain (1.8%), acute coronary syndrome (0.6%), angina unstable (0.6%), cardiac failure congestive (0.6%), non-cardiac chest pain (0.6%).
The registry lists 171 participants at risk for serious adverse events, with 8 affected, and 171 at risk for other adverse events, with 34 affected. These figures describe the ranolazine group in this single-group study. They are not a comparison of treatment risks, and the record does not establish that the reported events were caused by ranolazine. Deaths are not reported in the registry record.
The serious adverse event terms listed include Chest pain (1.8%), Acute coronary syndrome (0.6%), Angina unstable (0.6%), Cardiac failure congestive (0.6%), Non-cardiac chest pain (0.6%), and Urinary tract infection (0.6%). The record does not report the denominator or counting rules for each listed term, or whether participants could contribute more than one term. The terms therefore should not be added together or treated as mutually exclusive categories.
Safety counts in a study without a control group can describe events recorded during the study, but they cannot show how event frequency compares with what would have occurred under another treatment or without treatment. These figures also do not, by themselves, characterize event timing, severity beyond the serious/non-serious classification, or causal attribution. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was designed to evaluate the WISQ in women with chronic angina treated with ranolazine, using the SAQ and other patient-reported or activity measures as points of comparison. It also identifies the primary statistical approach: regression of WISQ Total Score at 4 weeks on angina frequency, nitroglycerin use, and DASI at 4 weeks, summarized by R^2. That description clarifies the intended measurement question, but does not supply its answer.
The primary R^2 result is not reported in the registry record. Neither are confidence intervals or p-values for that endpoint. Thus, the posted record does not quantify the association between WISQ scores and the listed measures, or the precision of such an estimate. The record also does not report numerical findings for the secondary questionnaire comparisons, diary outcomes, DASI changes, or correlations. The stated aims cannot be treated as observed findings.
The study's design places an important boundary on interpretation. It was open-label, nonrandomized, and single-group, so it is not a controlled comparison of ranolazine with another treatment. Changes recorded during the study would not, by themselves, establish that ranolazine caused those changes. The study can address measurement questions through associations and questionnaire behavior, but treatment effectiveness cannot be inferred from the design description or the safety counts.
The result also cannot establish all aspects of questionnaire performance from one regression statistic. In general, validity, reliability, and responsiveness are related but distinct properties. Evidence about association with relevant measures may inform validity, while reliability and responsiveness require their own appropriate analyses. The registry states those aims but does not report their results.
The most defensible reading is therefore limited: the record documents a phase 4 measurement study and the intended primary analysis, but does not report the endpoint estimate needed to judge the primary result. The information recorded is insufficient to conclude whether the WISQ met a particular validation standard, how precisely it did so, or whether it performed better or worse than the SAQ.
13. Why This Trial Matters Statistically
This study addresses a statistical question that differs from the usual treatment-comparison question. A clinical questionnaire is a measurement instrument, and its usefulness depends on whether its scores meaningfully reflect the experiences and functions it is intended to assess. The registry's focus on evaluating a female-specific angina questionnaire makes measurement properties—not just symptom change during treatment—the central concern.
Comparing WISQ items with corresponding SAQ items and examining relationships with angina frequency, nitroglycerin use, and DASI can be part of a broader validation strategy. In general, multiple kinds of evidence are useful because a single association or model-fit statistic cannot establish every property of an instrument. Validity, reliability, and responsiveness each concern different aspects of measurement. The study's stated aims recognize this distinction, although the registry record does not report the corresponding estimates.
The design also illustrates why statistical interpretation must follow the study question. A single-group, open-label study can examine questionnaire behavior among treated participants, but it cannot offer a randomized treatment contrast. Separating evidence about a measurement tool from evidence about treatment effects prevents an association or change from being interpreted as proof of a treatment benefit.
Finally, the record makes the gap between a defined analysis and an interpretable result clear. It specifies an R^2-based primary endpoint and a modified intent-to-treat population, yet does not report the primary estimate or the number analyzed. Without those results, readers can understand the intended method but cannot assess the magnitude or precision of the primary finding. That distinction is important when using registry information to evaluate both the design and the evidence actually recorded.
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 principal limitation for interpreting this study is that the registry record does not report the primary R^2 estimate or its uncertainty. It also does not report numerical results for the listed secondary outcomes. The aims and endpoint definitions therefore cannot be used as substitutes for findings.
The study was open-label, nonrandomized, and single-group. This is compatible with examining questionnaire relationships, but it limits causal interpretation of changes during treatment and offers no randomized comparator for estimating a treatment contrast. The registry record does not report a control group, so the study cannot establish how the observed course would compare with another treatment.
The primary endpoint is described with a Baseline to Week 4 timeframe, while the specified regression relates WISQ Total Score at 4 weeks to other week-4 measures. The registry record does not explain whether baseline values or changes from baseline were included in the model. That ambiguity limits a precise reading of what the primary regression estimates.
The primary analysis set requires completed baseline and postbaseline questionnaires, but its size is not reported in the registry record. Partially missing questionnaire responses were imputed according to scoring instructions, but the procedure is not described. Handling of completely missing responses, the extent of missing data, and sensitivity analyses are not reported in the registry record.
The registry lists 10 outcome measures and 3 analyses, but does not report a multiplicity strategy or a complete statistical analysis plan. It also does not report the trial's sample-size justification. The posted safety figures are descriptive and have no control-group comparison; deaths are not reported in the registry record. These limitations restrict conclusions about precision, robustness, and causal attribution.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Female-specific Angina Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041) — NCT00644332.
- Registry record last updated 2012-07-02; status last verified 2012-05.
- Results first posted 2012-07-02.
- 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.
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18. Record Summary
NCT00644332 is a completed phase 4, open-label, multicenter, nonrandomized, single-group study of ranolazine in women with chronic angina. Enrollment was 172; the study began in 2007-11, and primary completion was 2011-01. Its main objective was to evaluate the validity, reliability, and responsiveness of the WISQ, with the SAQ and other symptom and activity measures also included in the stated aims.
The primary endpoint was an R^2 from regression of WISQ Total Score at 4 weeks on 4-week angina frequency, nitroglycerin use, and DASI score. The primary analysis population required at least 1 dose of ranolazine and completed baseline and postbaseline questionnaires. The primary estimate, its uncertainty, and the size of that analysis population are not reported in the registry record. Safety figures list 8 participants affected by serious adverse events and 34 by other adverse events among 171 at risk in each category.