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 Study Evaluating The Effects Of Bazedoxifene/Conjugated Estrogens On Endometrial Safety And Postmenopausal Osteoporosis (NCT00808132), a randomized phase 3 study. The primary outcome is Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00808132 |
| Phase | Phase 3 |
| Condition | Menopause, Osteoporosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 1886 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Postmenopausal women were enrolled in a study addressing menopause and osteoporosis. The registry reports enrollment of 1886. The primary endpoint population is described as the efficacy evaluable population, with eligibility involving treatment exposure and endometrial biopsy information. The registry’s description of that population ends mid-criterion; the complete eligibility definition is not reported in the registry record.
Intervention
The study included bazedoxifene 20 mg combined with conjugated estrogens 0.45 mg, and bazedoxifene 20 mg combined with conjugated estrogens 0.625 mg. Other study arms received bazedoxifene 20 mg alone, conjugated estrogens 0.45 mg with medroxyprogesterone acetate 1.5 mg, or placebo.
Comparator
The design included both placebo and active controls. The registry lists five arms, but does not identify one single comparator for every intervention or provide the primary endpoint estimates for comparisons between arms. The particular comparison used for any reported primary analysis is not reported in the registry record.
Primary question
The primary endpoint asked what percentage of participants in the main study had endometrial hyperplasia at Month 12, assessed through endometrial biopsies. The study also evaluated menopausal symptoms and osteoporosis prevention, with secondary measures including bone mineral density and other outcomes. The registry record does not report the primary endpoint percentages, confidence intervals, or a between-arm effect estimate, so the comparative result cannot be described.
3. Trial Design
This was a phase 3, randomized, quadruple-masked, parallel-group study with placebo and active controls. The registry lists five treatment arms: two bazedoxifene/conjugated estrogens combinations, bazedoxifene alone, conjugated estrogens with medroxyprogesterone acetate, and placebo. The listed doses are bazedoxifene 20 mg with conjugated estrogens 0.45 mg or 0.625 mg; bazedoxifene 20 mg alone; and conjugated estrogens 0.45 mg with medroxyprogesterone acetate 1.5 mg.
The registry reports enrollment of 1886. It describes the study purpose as evaluating safety and effectiveness for menopausal symptoms while protecting the endometrium and preventing postmenopausal osteoporosis. The stated duration of participant participation was approximately 14.5 months. The primary endpoint was assessed at Month 12, and several secondary outcomes were measured at specified follow-up points.
The study began in 2009-01, reached primary completion in 2011-02, and is recorded as completed. The sponsor was Pfizer. Randomized allocation and a parallel model indicate that participants were assigned to treatment groups for comparison. Quadruple masking indicates that the record classifies the study as masked at four levels, but the identities of those levels and the practical masking procedures are not reported in the registry record.
The registry lists 13 outcome measures and 153 analyses. It does not provide a detailed account of randomization procedures, allocation concealment, the role of each masked party, site structure, adherence procedures, or the study’s sample-size justification. Those design details are not reported in the registry record. The reported enrollment should not be treated as the size of the primary endpoint analysis population: the primary outcome description specifies an efficacy evaluable population, and its complete definition and analyzed size are not reported.
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: This main study also included 3 sub-studies only for the purpose of the assessment of relevant parameters: breast density sub-study, osteoporosis sub-study (OSS), and sleep sub-study. A participant could participate in more than 1 sub-study.
Overall Study
| Stage | Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | Bazedoxifene 20 mg | Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | Placebo |
|---|---|---|---|---|---|
| STARTED | 455 | 481 | 239 | 228 | 483 |
| Treated | 445 | 474 | 230 | 220 | 474 |
| COMPLETED | 357 | 393 | 185 | 159 | 383 |
| NOT COMPLETED | 98 | 88 | 54 | 69 | 100 |
Reasons for not completing this period:
| Reason | Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | Bazedoxifene 20 mg | Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | Placebo |
|---|---|---|---|---|---|
| Adverse Event | 34 | 33 | 16 | 31 | 33 |
| Death | 0 | 0 | 0 | 0 | 1 |
| Physician Decision | 0 | 1 | 0 | 0 | 0 |
| Lost to Follow-up | 8 | 10 | 11 | 8 | 9 |
| Protocol Violation | 8 | 9 | 4 | 9 | 5 |
| Withdrawal by Subject | 27 | 18 | 2 | 7 | 16 |
| Other | 6 | 4 | 6 | 2 | 15 |
| Randomized, but not treated | 10 | 7 | 9 | 8 | 9 |
| Unsatisfactory response | 5 | 6 | 6 | 4 | 12 |
Analysis population for the primary outcome, as defined in the registry: Efficacy evaluable (EE) population included all randomized participants who took at least 1 dose of study drug, who had a screening endometrial biopsy with readings by at least 2 blinded central pathologists, had a biopsy during Month 12, or had hyperplasia diagnosed before Month 12 and had no major protocol violations.
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.
Population: Safety population included all randomized participants who received at least one dose of study drug.
| Characteristic | Unit | Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | Bazedoxifene 20 mg | Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 445 | 474 | 230 | 220 | 474 | 1843 | |
| Age, Continuous | Years | 54.43 (SD 4.02) | 53.89 (SD 4.00) | 54.07 (SD 4.01) | 54.15 (SD 4.50) | 54.19 (SD 4.07) | 54.15 (SD 4.09) |
| Sex: Female, Male: Female | Participants | 445 | 474 | 230 | 220 | 474 | 1843 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study, measured over Month 12.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with endometrial hyperplasia at Month 12 in the main study. Hyperplasia was assessed using endometrial biopsies, which were read centrally by two primary pathologists. If their readings disagreed on whether hyperplasia was present, a third pathologist was consulted. The endpoint therefore depends on both the biopsy assessment and the rule used to classify readings.
The registry describes two definitions. Under the first, a participant was considered to have hyperplasia when the three pathologists disagreed but at least one determined that hyperplasia was present. Under the second, at least two of the three pathologists had to agree on the diagnosis. These rules can classify some disputed cases differently, so the definition matters when interpreting an endpoint percentage. Numerical results for either definition are not reported in the registry record.
As a general statistical consideration, an endpoint based on a diagnostic assessment can provide a standardized way to compare groups when the assessment procedure and classification rule are clearly specified. Here, the endpoint addresses endometrial safety, a stated focus of the study. The record does not report the endpoint percentages, confidence intervals, or the comparison-specific estimates needed to assess the observed results or their precision.
The described primary population was efficacy evaluable and depended on treatment exposure and biopsy information. Its definition is incomplete in the registry record, which ends before the full criteria are given. The analyzed population size and the handling of participants without the required biopsy information are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies endometrial hyperplasia at Month 12 as the primary endpoint, but it does not report the observed endpoint percentages or confidence intervals. Consequently, the posted record does not establish the direction or size of any difference between treatment groups, nor how precisely such a difference was estimated. No conclusion about the comparative primary outcome can be drawn from the information recorded.
The two diagnostic definitions are important to interpretation. One counts hyperplasia when at least one of three pathologists determines it is present despite disagreement; the other requires agreement by at least two pathologists. These are distinct classification rules. Without endpoint results under each rule, it is not possible to determine whether the findings were similar across definitions or whether classification choices affected the estimates.
The registry lists a randomized parallel-group design with placebo and active controls, but does not state which arm-to-arm contrasts were used for the primary analysis. Nor does the record provide the analysis population size, group-specific denominators for the primary endpoint, effect estimates, confidence intervals, or hypothesis-test results. These omissions prevent assessment of both the magnitude and precision of the primary comparison. The overall enrollment figure does not substitute for the analyzed denominator, because the primary endpoint is described for an efficacy evaluable population.
As a general statistical point, a confidence interval describes a range of values compatible with the data and the method used to calculate it. A narrow interval indicates greater precision than a wide interval, while neither interval width nor a point estimate alone establishes clinical importance. The registry states that the primary endpoint used a 95% confidence interval as its dispersion measure, but gives no numerical interval. Therefore, its precision cannot be characterized from the posted record.
The record lists secondary outcomes concerning lumbar spine and total hip bone mineral density, amenorrhea, breast density, bone turnover markers, sleep, and menopause-specific quality of life. It does not provide their numerical results in the registry record recorded for this analysis. Their presence in the outcome list indicates the breadth of measured domains, not the direction, size, or certainty of any effect.
There are also no reported primary endpoint results with which to evaluate consistency between the bazedoxifene/conjugated estrogens doses, bazedoxifene alone, the active control, and placebo. The treatment arms should not be ranked or described as differing on the endpoint based only on the design listing. The sponsor’s analysis, if reported elsewhere in the registry record, would be needed to support a result-specific interpretation; numerical sponsor estimates are not reported in the registry record.
In short, the record documents the endpoint, its assessment approach, and the study design, but not the results required to interpret efficacy or safety comparisons. This is a limitation of the available registry record, not evidence that a difference was absent or present.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group study with five arms and quadruple masking. Randomization is a general method for assigning participants to groups by chance; when implemented as planned, it is intended to reduce systematic differences between groups at the start of a study. A parallel-group design assigns each participant to a study group and compares outcomes across groups. The registry does not describe the randomization sequence, allocation concealment, or the procedures used to maintain masking, so those operational details are not reported in the registry record.
What does a percentage endpoint represent?
The primary outcome is a percentage of participants with endometrial hyperplasia at Month 12. In general, an event percentage describes how many participants in a defined analysis group met the endpoint, relative to the group denominator used for that analysis. Such percentages are interpretable only alongside the relevant denominator, endpoint definition, and analysis population. The registry gives the endpoint description and two diagnostic definitions, but not the resulting percentages or denominators.
Because this is an event outcome, the classification of each participant as having or not having hyperplasia is central to the analysis. A biopsy was read centrally by two primary pathologists, with a third consulted when the first two disagreed about the presence of hyperplasia. The registry then defines two ways to use those readings. This makes the diagnostic rule part of the statistical definition of the endpoint, rather than a minor descriptive detail. The record does not state which definition was designated as the principal one for a particular reported comparison, and it does not give results under either definition.
How should a confidence interval be understood?
The primary endpoint’s stated dispersion measure is a 95% confidence interval. In general, a confidence interval conveys uncertainty around an estimated quantity under the assumptions of the calculation method. It helps readers judge the precision of an estimate: estimates with wider intervals are less precise than estimates with narrower intervals. The interval is not a guarantee that the true value lies within its bounds, and it does not by itself answer whether an effect is important. Interpretation also requires the point estimate, the comparison being made, and the interval limits. None of those numerical primary endpoint results is reported in the registry record.
A confidence interval for an individual group’s percentage and an interval for a difference between groups answer different questions. A group-specific interval describes uncertainty about that group’s event percentage. A comparative interval describes uncertainty about a contrast between groups. The registry identifies the endpoint’s confidence interval as a dispersion measure but does not provide enough detail or results to characterize the specific numerical estimates or comparisons.
Why do the analysis population and denominator matter?
The primary endpoint is described for an efficacy evaluable population. The recorded definition says participants had to be randomized, take at least one dose, and have specified screening and follow-up biopsy information, or have hyperplasia diagnosed before Month 12 without a major criterion that is cut off in the registry text. Since the description is incomplete, the full inclusion rules are not reported in the registry record. The number analyzed in this population and the group-specific denominators are also not reported.
As a general matter, an efficacy evaluable analysis can differ from an analysis of all randomized participants if participants are excluded for missing assessments or other criteria. Such exclusions can affect interpretation if inclusion depends on events after randomization. The registry record does not provide enough information to determine how exclusions were applied, whether a separate all-randomized analysis was conducted, or how missing endpoint assessments were handled. No assumption about those procedures is warranted.
What can the study design establish?
Randomization can support comparisons between assigned groups by helping balance factors at baseline, while masking can reduce the influence of knowledge about assignment on some study activities. These are general methodological purposes, not proof that every source of bias was prevented. The record confirms randomized allocation and quadruple masking, but does not describe the masking roles, implementation, or departures from assignment. It also does not report the primary outcome estimates needed to assess the results.
The registry states that there were 153 analyses and lists 13 outcome measures. In general, when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for multiplicity. Whether and how that issue was addressed depends on the prespecified analysis plan, including which outcomes and contrasts were confirmatory. The statistical analysis plan and multiplicity procedures are not reported in the registry record. The number of analyses alone does not establish which analyses were primary, prespecified, or adjusted.
The record includes a general planning illustration based on the 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. No numerical planning results are reported in the registry record recorded. In general, sample-size illustrations depend on assumptions about the effect, variability or event frequency, significance level, allocation, and analysis method. They are planning scenarios, not evidence that a study had a particular probability of detecting an effect after the data were observed. The trial’s own sample-size justification and the numerical illustration outputs are not reported in the registry record.
Finally, no interim-analysis procedures, stopping boundaries, missing-data sensitivity analyses, or statistical software details are reported in the registry record. These methods could affect how estimates are generated or interpreted, but their absence from the record does not establish that they were or were not used. The supported interpretation is limited to the design and endpoint details that are recorded and the fact that numerical primary outcome results are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures and 153 analyses, spanning the primary endpoint and secondary measures of bone mineral density, amenorrhea, breast density, bone turnover markers, sleep, and menopause-specific quality of life. Multiple outcomes and comparisons can create a multiplicity issue: as a general statistical principle, examining many hypotheses can increase the chance of obtaining at least one apparently notable result by chance if no adjustment or hierarchy is used. The number of listed analyses does not reveal which were prespecified, confirmatory, or exploratory. The analysis hierarchy, multiplicity adjustment, and detailed statistical plan are not reported in the registry record.
The primary endpoint description specifies an efficacy evaluable population, with requirements involving treatment exposure and biopsy readings. Its definition is cut off in the registry record, and the number of participants analyzed is not reported. The record does not state whether an intention-to-treat analysis was performed, how participants without Month 12 biopsy data were handled, whether missing data were imputed, or whether sensitivity analyses were conducted. Those details are not reported in the registry record.
As a general consideration, missing endpoint data can affect an estimate when the availability of measurements is related to treatment assignment or the outcome. The extent and direction of any such effect cannot be assessed without information about missingness, denominators, and analytic assumptions. No claim about the amount or handling of missing data is supported by the registry information recorded.
The registry also does not report interim analyses or their procedures. Their presence or absence should not be inferred. Since primary endpoint estimates and analysis details are unavailable, neither multiplicity handling nor the robustness of the reported analysis can be evaluated from this record.
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 |
|---|---|---|---|
| Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | 16 | 445 | 3.6% |
| Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | 17 | 474 | 3.6% |
| Bazedoxifene 20 mg | 5 | 230 | 2.2% |
| Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | 13 | 220 | 5.9% |
| Placebo | 18 | 474 | 3.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | 407 of 445 |
| Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | 426 of 474 |
| Bazedoxifene 20 mg | 207 of 230 |
| Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | 197 of 220 |
| Placebo | 423 of 474 |
Most frequent serious adverse event terms
| Event term | Organ system | Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | Bazedoxifene 20 mg | Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | Placebo |
|---|---|---|---|---|---|---|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 445 | 2 of 474 | 1 of 230 | 3 of 220 | 2 of 474 |
| Non-cardiac chest pain | General disorders | 1 of 445 | 0 of 474 | 1 of 230 | 1 of 220 | 1 of 474 |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 445 | 1 of 474 | 0 of 230 | 0 of 220 | 1 of 474 |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 445 | 1 of 474 | 0 of 230 | 0 of 220 | 1 of 474 |
| Myocardial infarction | Cardiac disorders | 1 of 445 | 0 of 474 | 0 of 230 | 0 of 220 | 1 of 474 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 445 | 0 of 474 | 0 of 230 | 0 of 220 | 1 of 474 |
| Gastritis | Gastrointestinal disorders | 1 of 445 | 1 of 474 | 0 of 230 | 0 of 220 | 0 of 474 |
| Appendicitis | Infections and infestations | 1 of 445 | 1 of 474 | 0 of 230 | 0 of 220 | 0 of 474 |
| Patella fracture | Injury, poisoning and procedural complications | 0 of 445 | 0 of 474 | 1 of 230 | 0 of 220 | 1 of 474 |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | 2 of 445 | 0 of 474 | 0 of 230 | 0 of 220 | 0 of 474 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg | Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg | Bazedoxifene 20 mg | Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg | Placebo |
|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 96 of 445 | 109 of 474 | 48 of 230 | 54 of 220 | 122 of 474 |
| Nasopharyngitis | Infections and infestations | 91 of 445 | 72 of 474 | 44 of 230 | 32 of 220 | 65 of 474 |
| Back pain | Musculoskeletal and connective tissue disorders | 52 of 445 | 64 of 474 | 29 of 230 | 25 of 220 | 65 of 474 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 45 of 445 | 46 of 474 | 17 of 230 | 31 of 220 | 45 of 474 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 42 of 445 | 49 of 474 | 22 of 230 | 19 of 220 | 47 of 474 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 48 of 445 | 45 of 474 | 26 of 230 | 14 of 220 | 33 of 474 |
| Vaginal haemorrhage | Reproductive system and breast disorders | 30 of 445 | 29 of 474 | 14 of 230 | 37 of 220 | 36 of 474 |
| Sinusitis | Infections and infestations | 42 of 445 | 37 of 474 | 19 of 230 | 12 of 220 | 33 of 474 |
| Hot flush | Vascular disorders | 27 of 445 | 37 of 474 | 20 of 230 | 11 of 220 | 40 of 474 |
| Upper respiratory tract infection | Infections and infestations | 36 of 445 | 38 of 474 | 9 of 230 | 13 of 220 | 30 of 474 |
Serious events with the highest arm-level rate: basal cell carcinoma (1.4%), leukocytosis (0.5%), autoimmune thyroiditis (0.5%), non-cardiac chest pain (0.5%), pyrexia (0.5%).
The registry lists serious adverse event counts and counts for other reported adverse events by arm. For serious adverse events, the listed counts are 16 among 445 at risk in the bazedoxifene 20 mg/conjugated estrogens 0.45 mg arm; 17 among 474 at risk in the bazedoxifene 20 mg/conjugated estrogens 0.625 mg arm; 5 among 230 at risk in the bazedoxifene 20 mg arm; 13 among 220 at risk in the conjugated estrogens 0.45mg/medroxyprogesterone acetate 1.5mg arm; and 18 among 474 at risk in the placebo arm.
The corresponding counts for other reported adverse events are 407 among 445 at risk, 426 among 474 at risk, 207 among 230 at risk, 197 among 220 at risk, and 423 among 474 at risk, respectively. These are counts, not adjusted comparisons. The registry does not provide exposure time, a comparative effect estimate, or a statistical analysis for these figures, so they should not be treated as rates or as evidence of a between-arm difference.
The most frequent serious adverse event terms listed include basal cell carcinoma at 1.4%, and leukocytosis, autoimmune thyroiditis, non-cardiac chest pain, pyrexia, and cholecystitis, each at 0.5%. The registry’s definitions and event-term coding details are not reported in the registry record. Death counts are not reported in the registry record. These safety listings describe recorded events and do not establish causality or comparative risk.
12. What the Result Does, and Does Not, Mean
The registry record describes a phase 3 randomized study that compared two bazedoxifene/conjugated estrogens combinations, bazedoxifene alone, an active-control regimen, and placebo. Its main endpoint was the percentage of participants with endometrial hyperplasia at Month 12, assessed through centrally read biopsies under two stated diagnostic definitions. This documents what the study set out to measure and how the endpoint was classified.
It does not provide the primary endpoint percentages, confidence intervals, group denominators, or between-arm estimates. Therefore, the record does not support a conclusion about whether the groups differed, the direction or size of any difference, or the precision of an estimate. The missing results should not be interpreted as evidence for no effect, nor as evidence for a benefit or harm.
The listed secondary outcomes cover bone density, bone turnover, amenorrhea, breast density, sleep, and menopause-specific quality of life. Their inclusion shows that the study measured more than the primary endometrial endpoint, but their numerical results are not reported in the registry information recorded. Conclusions about those outcomes cannot be drawn from their titles alone.
The adverse event listings provide counts by arm and selected serious-event terms with percentages. They are descriptive registry entries, not adjusted comparisons or causal estimates. Without event definitions, follow-up exposure, analysis methods, and comparative statistics, the figures cannot establish that a treatment caused an event or changed its risk relative to another arm.
As a general statistical principle, study design and outcome results answer different questions. Randomization and masking describe how comparisons were intended to be conducted; estimates and uncertainty describe what the observed data show. The record documents the design but lacks the numerical primary outcome results required for a result-based conclusion. Its strongest supported contribution is therefore a description of the study question, treatment arms, endpoint assessment, and the limitations of the recorded results.
13. Why This Trial Matters Statistically
This study raises a statistical issue common to clinical trials that assess both safety-related and prevention outcomes: a clearly defined endpoint must be interpreted alongside its assessment rule, analysis population, and uncertainty. Here, endometrial hyperplasia was assessed by biopsy, with central pathology review and a third reader consulted when the initial readers disagreed. The registry also records two definitions of hyperplasia, making classification criteria directly relevant to the endpoint.
The design included multiple treatment arms and both placebo and active controls. That structure can support several clinically relevant comparisons, but it also makes it important to distinguish planned primary contrasts from other analyses. The registry lists 13 outcome measures and 153 analyses. Without the prespecified comparison hierarchy or multiplicity procedures, the role of each analysis cannot be determined from those counts alone.
The primary outcome was defined for an efficacy evaluable population rather than described simply as an outcome among everyone randomized. This makes the population definition and the handling of participants without required biopsy data important to interpretation. The registry’s description is incomplete, and it does not report the analyzed denominators or missing-data methods. Those gaps limit assessment of how the analysis population relates to the randomized groups.
Most importantly, statistical interpretation requires estimates and their precision. Although the registry specifies a 95% confidence interval for the primary endpoint, it does not report the interval or the endpoint percentages. The design and measurement details are informative, but they cannot substitute for comparative results. This distinction is central when reading registry records: a well-described question does not by itself show what the observed data imply.
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 limitation for interpreting this trial from the registry record is the absence of numerical primary endpoint results. Percentages of participants with endometrial hyperplasia, confidence intervals, group denominators, and between-arm estimates are not reported. The primary endpoint is described using two diagnostic definitions, but no results under either definition are recorded.
The endpoint analysis population is described as efficacy evaluable, but the recorded eligibility definition is incomplete and the analyzed size is not reported. The record also does not explain how missing or unreadable biopsies were handled, whether participants were analyzed according to randomized assignment, or whether sensitivity analyses were conducted. These omissions prevent assessment of how the analysis population and missing outcome data might affect interpretation.
The study had five arms and lists 13 outcome measures and 153 analyses. The registry does not report the prespecified analysis hierarchy, the primary comparison, adjustment for multiple testing, or a detailed statistical analysis plan. It is therefore not possible to identify which comparisons were confirmatory from the counts alone.
Other trial details relevant to appraisal—including the randomization procedure, allocation concealment, identities of the masked parties, adherence, protocol deviations, interim analyses, and the study’s own sample-size justification—are not reported in the registry record. The record also does not provide numerical results for the listed secondary outcomes. These limitations concern what can be interpreted from the recorded information; they do not establish that the omitted procedures or analyses were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Evaluating The Effects Of Bazedoxifene/Conjugated Estrogens On Endometrial Safety And Postmenopausal Osteoporosis — NCT00808132.
- Registry record last updated 2014-04-08; status last verified 2014-03.
- Results first posted 2013-12-20.
- 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.
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18. Record Summary
The registry describes NCT00808132 as a completed phase 3 randomized, quadruple-masked, parallel-group study sponsored by Pfizer. It reports enrollment of 1886 and lists five arms: two bazedoxifene/conjugated estrogens combinations, bazedoxifene alone, conjugated estrogens with medroxyprogesterone acetate, and placebo. The study began in 2009-01 and reached primary completion in 2011-02.
The primary endpoint was the percentage of participants with endometrial hyperplasia at Month 12, assessed by centrally read endometrial biopsies using two stated diagnostic definitions. The record lists 13 outcome measures and 153 analyses. It does not report numerical primary endpoint results or the detailed analysis information needed to evaluate those comparisons. Secondary outcomes include bone density, amenorrhea, breast density, bone turnover, sleep, and menopause-specific quality of life measures.