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 Dehydroepiandrosterone (DHEA) Against Vaginal Atrophy (NCT01358760), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01358760 |
| Phase | Phase 3 |
| Condition | Vaginal Atrophy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 450 |
| Arms in the primary outcome | n/a |
| Lead sponsor | EndoCeutics Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Postmenopausal women with vaginal atrophy were the intended population. The primary endpoint’s efficacy population is defined as the Intent to Treat (ITT) population: subjects who received at least one dose of study drug and had a baseline (Day 1) evaluation meeting the study entry criteria. The registry record does not give further eligibility details in the information recorded for this trial.
Intervention
The active interventions were intravaginal DHEA at 0.25% and 0.50%. The trial description identifies intravaginal dehydroepiandrosterone as the study treatment. The registry record does not give additional administration details in the arm descriptions.
Comparator
The comparator was placebo. The trial used a randomized, parallel-group design, and the adverse-event record lists placebo, 0.25% DHEA, and 0.50% DHEA groups. The primary endpoint description does not give group-specific results or specify a particular pairwise contrast.
Primary question
The primary outcome was change from baseline to Week 12 in the percentage of parabasal cells in the maturation index of a vaginal smear. The clinical question is whether the change in this cell-based measure differed across the randomized treatment groups. The registry record does not report the group means, treatment contrasts, confidence intervals, or a primary-outcome test, so the size and precision of any between-group difference cannot be described from this record.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group Phase III trial sponsored by EndoCeutics Inc. The registry record lists an enrollment of 450 and identifies vaginal atrophy as the condition. The study began in 2011-06, reached primary completion in 2012-04, and is recorded as completed. Those dates describe the registry timeline; they do not establish when results were analyzed or posted.
The interventions listed were placebo and two DHEA strengths, 0.25% and 0.50%. A parallel-group design assigns participants to one group for comparison with the other groups, rather than having each participant receive every intervention in sequence. Randomization is intended, in general, to reduce systematic differences between groups at the start of a trial. Masking is intended, in general, to limit the influence of treatment knowledge on participant behavior, care, outcome assessment, or analysis. The record labels masking as quadruple but does not identify which roles were masked or describe how masking was maintained.
The enrollment figure is a trial-level registry count; it should not be treated as the number contributing data to every endpoint. For the primary efficacy outcome, the stated ITT population includes participants who received at least one dose and had a qualifying baseline evaluation. The registry record does not provide endpoint-specific denominators or explain whether all enrolled participants met that definition.
Several secondary outcomes concern changes through Week 12, including dyspareunia and assessments of vaginal atrophy based on secretions, epithelial integrity, epithelial surface thickness, and vaginal color. The record lists nine outcome measures overall, but does not provide numerical results for the primary endpoint in the information available for this analysis. It also does not describe the randomization procedure, allocation concealment, treatment adherence, or details of the study-drug regimen.
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
| Stage | Placebo | 0.25% DHEA | 0.50% DHEA |
|---|---|---|---|
| STARTED | 152 | 148 | 150 |
| Safety Population | 150 | 143 | 148 |
| ITT Population | 139 | 134 | 134 |
| COMPLETED | 130 | 128 | 125 |
| NOT COMPLETED | 22 | 20 | 25 |
Reasons for not completing this period:
| Reason | Placebo | 0.25% DHEA | 0.50% DHEA |
|---|---|---|---|
| Adverse Event | 3 | 4 | 3 |
| Lost to Follow-up | 1 | 1 | 3 |
| Withdrawal by Subject | 5 | 3 | 2 |
| Physician Decision | 1 | 0 | 1 |
| Entry criteria not met/Non-compliance | 12 | 12 | 16 |
Analysis population for the primary outcome, as defined in the registry: Efficacy analyses were performed primarily on the Intent to Treat (ITT) population defined as all subjects who have received at least one dose of study drug with a baseline (Day 1) evaluation meeting the study entry criteria.
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: Baseline Analysis Population corresponds to the Safety Population which includes all subjects who received any amount of DHEA (prasterone) or placebo, and who have any safety information available.
| Characteristic | Unit | Placebo | 0.25% DHEA | 0.50% DHEA | Total |
|---|---|---|---|---|---|
| Participants analysed | 150 | 143 | 148 | 441 | |
| Age, Continuous | years | 57.59 (SD 6.47) | 58.41 (SD 6.02) | 58.33 (SD 6.16) | 58.11 (SD 6.22) |
| Sex/Gender, Customized: Female | Participants | 150 | 143 | 148 | 441 |
| Race/Ethnicity, Customized: White caucasian | Participants | 135 | 132 | 131 | 398 |
| Race/Ethnicity, Customized: Black or African American | Participants | 12 | 9 | 13 | 34 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 1 | 1 | 3 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 1 | 3 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear, measured over Baseline and Week 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | percentage of parabasal cells |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline to Week 12 in the percentage of parabasal cells in the maturation index of the vaginal smear. A central laboratory classified a 100-cell count from vaginal smears as parabasal cells, including basal cells, intermediate cells, or superficial squamous cell types. The reported measure is the percentage classified as parabasal, and the endpoint description says baseline values, Week 12 values, and change were presented.
This is a continuous, cell-based measure. In general, a continuous endpoint can retain more gradation than an outcome recorded only as a category, while a laboratory-based cell classification can provide a defined way to assess tissue-related change. These are general statistical and measurement considerations; they do not establish that the measure captures every aspect of vaginal atrophy or of how participants feel.
The primary endpoint focuses on change over the stated assessment interval. Comparing change between randomized groups can help distinguish observed change during treatment from change also seen in a comparator group. The registry record does not report the actual baseline or Week 12 means, the mean changes, a treatment contrast, or uncertainty around an estimate. Accordingly, the direction, magnitude, and precision of the primary endpoint result cannot be evaluated from the record. The endpoint’s clinical interpretation or a threshold for an important change is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clear primary outcome and its measurement procedure, but the numerical primary-outcome results needed to interpret treatment-group differences are not reported in the registry record. There are no group means, mean changes, estimated contrasts, confidence intervals, or primary-outcome p-values in the registry record recorded for this analysis. Without those estimates, it is not possible to describe whether the groups changed in different directions, how large any difference was, or how precisely it was estimated.
The record specifies that the endpoint is a mean of a continuous measure and that dispersion is expressed as a standard error. In general, the mean describes the average value in a group, while the standard error describes the estimated precision of that average. A standard error is not a description of the spread of individual participant measurements; that is a different quantity. Because numerical means and standard errors are absent, neither group averages nor their precision can be discussed.
The primary efficacy population is described as an ITT population consisting of participants who received at least one dose and had a qualifying baseline evaluation. The record does not state how many participants met this definition for the primary endpoint, how many contributed Week 12 data, or how missing observations were handled. The enrollment count alone cannot substitute for endpoint-specific denominators.
The listed secondary outcomes cover several symptoms and assessments of vaginal atrophy through Week 12. Their presence indicates that the trial assessed more than the primary cell-based endpoint, but their numerical findings are not included in the registry record for this analysis. The registry record also does not report whether or how conclusions across multiple outcomes were adjusted or prioritized beyond identifying the primary endpoint.
Safety counts are recorded for serious and other adverse events in each group. The serious-event counts are 5 among 150 at risk in the placebo group, 1 among 143 at risk in the 0.25% DHEA group, and 1 among 148 at risk in the 0.50% DHEA group. Other adverse-event counts are 19 among 150, 17 among 143, and 23 among 148, respectively. These are descriptive group counts; the record does not provide comparative safety estimates or uncertainty intervals. The list of serious-event terms gives six terms, each with a reported 0.7%, without linking those terms to particular groups in the information recorded.
These observations should not be turned into a claim that one intervention is effective or ineffective, or safer or less safe. The primary efficacy estimates and a detailed comparative analysis are absent. The most defensible reading is that the registry record documents the trial design, the planned primary measure, and selected safety counts, but does not contain enough numerical efficacy information to estimate the primary treatment contrast or its precision.
9. Statistical Methods Explained
The primary outcome is described as a mean of a continuous measure: change in the percentage of parabasal cells from baseline to Week 12. For a continuous endpoint, a group mean gives the average observed value, and a comparison of group means can estimate an average difference. In general, an estimate is more informative when accompanied by an interval expressing uncertainty, because a point estimate alone does not show how precisely the effect has been measured. No primary group means, contrasts, or confidence intervals are reported in the registry record, so those quantities cannot be interpreted for this trial.
What does a standard error describe?
The registry record identifies standard error as the dispersion measure for the primary endpoint. In general, a standard error describes the uncertainty of an estimated mean, rather than the variability among individual participants. A confidence interval is generally constructed from an estimate and its standard error, using assumptions appropriate to the analysis. It expresses a range of values compatible with the data and method, not a guarantee that the true effect falls inside that particular interval. No numerical standard errors or confidence intervals for the primary endpoint are reported in the registry record.
Why compare change from baseline?
Change scores use both a baseline measurement and a follow-up measurement. In general, comparing average changes can describe how groups changed during the same follow-up period. A randomized comparison is useful because, on average, random assignment is intended to balance both measured and unmeasured starting characteristics. That intention does not ensure perfect balance in a particular trial, and adjustment methods can matter. The registry record does not describe whether the primary analysis adjusted for baseline values or used another model for repeated or follow-up measurements. It also does not report an estimated between-group change contrast.
What do the sample-size illustrations mean?
The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect considered is a stated fraction of the observed effect. These are planning calculations, not the trial’s reported design justification and not a measure of observed power. In general, a planning calculation asks how much information would be needed to detect an assumed effect under stated assumptions. It depends on the effect chosen, variability, allocation, and analysis method. Because the numerical illustrations are not included in the registry record for this analysis, no values for participants per arm can be stated. The record does not report the trial’s own sample-size justification.
Power is a prospective property of a specified design and assumed effect. It is not a useful substitute for an observed estimate and its uncertainty after data are collected. A calculation based on an observed effect can be especially difficult to interpret as evidence because the observed effect is itself uncertain. The planning illustrations should therefore be read only as hypothetical sample-size requirements under their stated assumptions, never as proof that the trial had a particular probability of detecting a real effect.
Why can over-dispersion matter?
In general, over-dispersion means that observed variation is greater than a statistical model expects. When a model assumes less variation than the data contain, standard errors can be too small and confidence intervals too narrow, making results appear more precise than they are. The primary outcome is described as a continuous mean, and the registry record does not identify a count model or report a test for over-dispersion. This general concept should not be mistaken for a finding about this trial.
For cell-based percentages, the measurement is bounded and is derived from a 100-cell count. In general, bounded measurements and counts can have distributional features that influence the choice of model, but the appropriate analysis depends on the observed data and prespecified method. The registry record does not report distributional checks, transformations, robust standard errors, or model diagnostics. No assumption about these procedures can be made from the outcome description alone.
What can the adverse-event counts establish?
Safety counts provide descriptive information about the number of participants recorded with events in the listed groups and the numbers at risk. In general, a comparative safety analysis may also need defined follow-up, event definitions, exposure information, and uncertainty estimates. The registry record provides serious and other adverse-event counts by group, but does not report comparative risk estimates, confidence intervals, event rates over person-time, or a statistical test. The term percentages are presented without treatment-group assignments in the recorded details. These entries should therefore be treated as descriptive, not as a formal demonstration of a difference.
The registry lists no numerical primary analysis under analyses recorded, while identifying nine outcome measures. That does not establish that no analysis was conducted; it describes what is recorded in the registry record. Likewise, the specified endpoint and population definition do not reveal the complete statistical analysis plan. The method used for hypothesis testing, handling of missing measurements, covariate adjustment, multiplicity, and sensitivity analyses is not reported in the registry record. General principles explain why these details matter, but they cannot fill in the trial-specific methods that are not documented.
10. Multiplicity, Missing Data and Analysis Populations
The record identifies one primary outcome and lists secondary outcomes that include dyspareunia and several assessments of vaginal atrophy through Week 12. It also records nine outcome measures overall. When several outcomes or treatment contrasts are tested, the chance of obtaining at least one apparently notable result by chance can increase. In general, a prespecified hierarchy, adjustment procedure, or clearly descriptive interpretation can help address this multiplicity. The registry record does not report whether an adjustment was planned or used, how secondary outcomes were prioritized, or whether multiple comparisons were otherwise handled.
The primary population is defined as participants who received at least one dose and had a baseline Day 1 evaluation meeting entry criteria. This is the registry’s stated ITT definition for efficacy analyses. The record does not report how many participants were included in this population for each outcome, how many lacked Week 12 measurements, or how missing data were handled. It does not describe imputation, a complete-case approach, a repeated-measures model, or sensitivity analyses. These methods can lead to different assumptions about participants without observed follow-up values, so the absence of a description limits assessment of potential bias.
The registry record also does not specify whether the primary analysis followed a prespecified statistical plan, whether any interim analyses took place, or whether the reported endpoint analysis was adjusted for baseline measurements. These details are not reported in the registry record and should not be inferred from the trial’s Phase III designation or randomized design. In the absence of numerical primary estimates and analysis details, it is not possible to assess the robustness of the efficacy conclusions.
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 |
|---|---|---|---|
| Placebo | 5 | 150 | 3.3% |
| 0.25% DHEA | 1 | 143 | 0.7% |
| 0.50% DHEA | 1 | 148 | 0.7% |
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 |
|---|---|
| Placebo | 19 of 150 |
| 0.25% DHEA | 17 of 143 |
| 0.50% DHEA | 23 of 148 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | 0.25% DHEA | 0.50% DHEA |
|---|---|---|---|---|
| Gastritis erosive | Gastrointestinal disorders | 1 of 150 | 0 of 143 | 0 of 148 |
| Pancreatitis | Gastrointestinal disorders | 1 of 150 | 0 of 143 | 0 of 148 |
| Small intestinal obstruction | Gastrointestinal disorders | 1 of 150 | 0 of 143 | 0 of 148 |
| Cellulitis | Infections and infestations | 0 of 150 | 0 of 143 | 1 of 148 |
| Movement disorder | Nervous system disorders | 0 of 150 | 1 of 143 | 0 of 148 |
| Stress | Psychiatric disorders | 1 of 150 | 0 of 143 | 0 of 148 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 1 of 150 | 0 of 143 | 0 of 148 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | 0.25% DHEA | 0.50% DHEA |
|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | 9 of 150 | 10 of 143 | 14 of 148 |
| Nasopharyngitis | Infections and infestations | 10 of 150 | 7 of 143 | 9 of 148 |
Serious events with the highest arm-level rate: movement disorder (0.7%), cellulitis (0.7%), gastritis erosive (0.7%), pancreatitis (0.7%), small intestinal obstruction (0.7%).
The adverse-event record gives group counts and numbers at risk. Serious adverse events were recorded for 5 of 150 participants at risk in the placebo group, 1 of 143 in the 0.25% DHEA group, and 1 of 148 in the 0.50% DHEA group. Other adverse events were recorded for 19 of 150, 17 of 143, and 23 of 148, respectively. These are counts as recorded, not adjusted comparisons between groups.
In general, serious and non-serious adverse-event summaries answer different descriptive questions; a serious event is not simply an event with a higher numerical count. The record does not provide definitions, exposure-adjusted rates, comparative estimates, confidence intervals, or a statistical test for these figures. It also does not report deaths in the recorded safety information. That is not the same as establishing that no deaths occurred.
Six serious-event terms are listed, each with a reported 0.7%: movement disorder, cellulitis, erosive gastritis, pancreatitis, small intestinal obstruction, and stress. The registry record does not link these terms to a treatment group in the information recorded. Small counts and descriptive entries should be read cautiously; they do not by themselves establish a causal relationship or a reliable difference between treatments.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of placebo with two intravaginal DHEA strengths in a Phase III trial of postmenopausal women with vaginal atrophy. It specifies a laboratory-based primary endpoint: change from baseline to Week 12 in the percentage of parabasal cells in the vaginal smear maturation index. The measurement procedure includes a central laboratory’s classification of a 100-cell count. This defines what the primary outcome was intended to measure.
However, the record does not give the primary outcome’s numerical results. Without group-specific changes, a between-group estimate, and an uncertainty interval, it is not possible to tell from this record how large or precise a difference was. It is also not possible to determine whether any observed difference was clinically important, because no threshold for clinical importance is reported in the registry record. The absence of numerical estimates is a limit on interpretation, not evidence that there was no effect.
The endpoint is a cell-based measure, while the listed secondary outcomes include symptoms and other assessments of vaginal atrophy. In general, outcomes can capture different aspects of a condition and need not move together. A change in one laboratory measure would not, by itself, establish a change in every symptom or assessment. The registry record does not report numerical results for those secondary outcomes in the registry record recorded for this analysis.
The safety entries describe event counts but do not constitute a complete comparative safety analysis. They do not establish that an event was caused by a study intervention, and the record does not supply uncertainty estimates for group comparisons. The serious-event terms are listed without a treatment-group link in the recorded information. The absence of a death count is not evidence that no deaths occurred.
Overall, the record supports a description of the trial’s design, outcome definition, population definition, and selected adverse-event counts. It does not support a conclusion about the magnitude, precision, clinical importance, or statistical significance of the primary efficacy comparison. It also does not supply enough detail to evaluate missing-data methods, multiplicity control, or the full analysis plan.
13. Why This Trial Matters Statistically
This trial illustrates why a registered endpoint and a numerical result are different kinds of evidence. The registry record describes a specific primary measure and its laboratory procedure, but does not report the estimates needed to judge the treatment contrast. A well-defined outcome improves transparency about what was to be measured; it cannot substitute for group results and uncertainty estimates.
The endpoint also highlights the distinction between measurement and interpretation. A 100-cell classification provides a stated basis for calculating the percentage of parabasal cells, while the clinical importance of a particular change requires additional context. The record does not identify a threshold for an important change, and it does not report the primary result. Statistical analysis can quantify uncertainty around an estimate, but statistical precision alone does not determine clinical importance.
The trial’s three groups and multiple outcomes raise general questions about contrast selection and multiplicity. A reader needs to know which comparisons were primary, how secondary analyses were handled, and how missing follow-up data were addressed. Those analysis details are not reported in the registry record. Their absence limits a full statistical appraisal even though the trial’s randomized, masked, parallel design is documented.
Finally, adverse-event counts show why descriptive data should not be mistaken for comparative evidence. Counts and denominators provide a basic accounting, but they do not by themselves quantify uncertainty or establish causation. The registry record’s combination of design information, endpoint definition, and limited numerical safety data therefore supports careful description, while leaving important efficacy and methods questions unresolved.
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 central limitation for interpreting efficacy is that the registry record does not report numerical results for the primary endpoint. No group means, changes, treatment contrasts, confidence intervals, or primary-outcome tests are included in the registry record recorded for this analysis. The result’s direction, magnitude, and precision therefore cannot be assessed.
The record identifies an ITT efficacy population, but does not give the number included in each primary-outcome analysis or the number with Week 12 data. It does not describe missing-data handling, baseline adjustment, model specification, or sensitivity analyses. These omissions prevent assessment of how incomplete follow-up or analytical choices may have influenced estimates.
Although nine outcome measures are listed, the record does not explain the approach to multiplicity or provide the numerical secondary-outcome findings in the registry record recorded for this analysis. It also does not report a clinical-importance threshold for the primary measure. The primary measure is a cell-based percentage, so it cannot be assumed to represent all symptoms or other aspects of vaginal atrophy.
The safety information is limited to counts and denominators for serious and other adverse events, plus a list of serious-event terms with percentages. Comparative estimates, uncertainty intervals, detailed event definitions, exposure-adjusted summaries, and treatment-group assignments for the listed terms are not reported in the registry record. Deaths are not numerically reported in the recorded safety information; that omission should not be interpreted as zero deaths.
The record does not describe allocation concealment, the roles included in quadruple masking, adherence, interim analyses, or the trial’s sample-size justification. These trial-specific methods are not reported in the registry record. The stated sample-size illustrations are planning calculations based on the observed effect, not evidence about observed power or a substitute for the missing primary estimate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dehydroepiandrosterone (DHEA) Against Vaginal Atrophy — NCT01358760.
- Registry record last updated 2017-06-12; status last verified 2017-06.
- Results first posted 2017-06-12.
- 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
This completed Phase III randomized, quadruple-masked, parallel-group trial evaluated intravaginal DHEA against placebo in postmenopausal women with vaginal atrophy. The registry record lists enrollment of 450, a start in 2011-06, and primary completion in 2012-04. The active groups are identified as 0.25% and 0.50% DHEA.
The primary outcome was change from baseline to Week 12 in the percentage of parabasal cells in the vaginal smear maturation index, based on a central-laboratory 100-cell classification. The stated efficacy population was an ITT population requiring at least one dose and a qualifying baseline evaluation.
The record lists nine outcome measures and provides descriptive serious and other adverse-event counts by group. Numerical primary efficacy results, detailed analysis methods, missing-data procedures, and multiplicity handling are not reported in the registry record. The available information therefore describes the study’s design and endpoint but does not permit an estimate of the primary treatment difference or its precision.