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 Treatment Of Hot Flashes/Flushes In Postmenopausal Women (WARM Study) (NCT00604825), a randomized phase 2 study. The primary outcome is Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00604825 |
| Phase | Phase 2 |
| Condition | Menopausal and Female Climacteric States |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 356 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy postmenopausal women with moderate to extremely severe vasomotor symptoms. The safety population was defined as randomized participants who received at least one dose of investigational product.
Intervention
Oral GSK232802, studied at 25 mg and 75 mg as monotherapy for 12 weeks.
Comparator
Placebo and Premarin 0.3 mg were the comparison groups listed in the posted results.
Primary question
How many participants experienced adverse events, serious adverse events, and adverse events judged mild, moderate, or severe during follow-up up to 21 weeks?
The registry describes the study’s broad purpose as evaluating the safety and efficacy of GSK232802 for reducing the frequency and severity of menopausal hot flashes. Its stated primary outcome, however, is a safety measure: counts of participants with adverse events and serious adverse events, together with counts by investigator-assessed severity. Frequency and severity of vasomotor symptoms were listed among the secondary outcomes, alongside quality-of-life, sleep, vaginal symptom, and fatigue measures.
This distinction matters when interpreting the posted results. The primary endpoint does not itself quantify change in hot-flash frequency or severity, and the registry record does not give a single primary efficacy contrast. It lists a randomized, parallel-group comparison among placebo, two GSK232802 doses, and Premarin. The record does not report a specific primary statistical comparison among those groups. Thus, the primary question addressed by the stated endpoint is about the observed safety counts during follow-up, not whether one treatment reduced symptoms more than another.
3. Trial Design
The WARM Study is listed as a phase 2, randomized, double-blind, parallel-group trial. It was placebo-controlled and included an active comparator. The registry identifies the interventions as placebo, GSK232802, and Premarin, and the posted group labels specify GSK232802 25 mg, GSK232802 75 mg, and Premarin 0.3 mg. The official title describes oral GSK232802 monotherapy for 12 weeks in healthy postmenopausal women with moderate to extremely severe vasomotor symptoms.
The record lists enrollment of 356 and describes the study as multicenter. It gives a start date of 2007-07-17 and a primary completion date of 2008-07-23, with status recorded as completed. The meaning of double masking is that treatment assignment is concealed from designated trial participants and personnel, but the registry record does not specify which roles were masked or how masking was maintained. Allocation is identified as randomized; the sequence-generation and allocation-concealment procedures are not reported in the registry record.
The primary outcome timeframe is up to 21 weeks. This is distinct from the 12-week treatment period described in the official title: the available record does not explain the relationship between treatment duration and the full safety follow-up window. Secondary outcomes include symptom changes at weeks 4 and 8, response thresholds at week 12, and several other patient-reported measures at listed visits. The registry record does not describe the visit schedule beyond the timepoints named for individual outcomes, nor does it report the number of study sites, group allocation ratio, dose-adjustment procedures, or detailed eligibility criteria.
The safety population comprises randomized participants who received at least one dose of investigational product. This population definition is the only explicit analysis-population definition in the record. It should not be assumed to be identical to the population used for every efficacy outcome, because those analysis populations are not reported in the registry record.
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: A total of 982 healthy postmenopausal participants with moderate to extremely severe vasomotor symptoms were screened (626 screen failures) and 356 were randomized.
Overall Study
| Stage | Placebo | GSK232802 25 mg | GSK232802 75 mg | Premarin 0.3 mg |
|---|---|---|---|---|
| STARTED | 90 | 87 | 89 | 90 |
| COMPLETED | 81 | 72 | 73 | 79 |
| NOT COMPLETED | 9 | 15 | 16 | 11 |
Reasons for not completing this period:
| Reason | Placebo | GSK232802 25 mg | GSK232802 75 mg | Premarin 0.3 mg |
|---|---|---|---|---|
| Adverse Event | 2 | 6 | 7 | 4 |
| Lost to Follow-up | 0 | 3 | 1 | 0 |
| Protocol Violation | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 4 | 3 | 5 | 5 |
| Lack of Efficacy | 3 | 2 | 1 | 0 |
| Did not meet eligibility criteria | 0 | 0 | 2 | 0 |
| Physician Decision | 0 | 0 | 0 | 1 |
| Exclusion criterion met | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety Population which comprised of all randomized participants who received at least one dose of investigational product.
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 | Placebo | GSK232802 25 mg | GSK232802 75 mg | Premarin 0.3 mg | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 90 | 87 | 89 | 90 | 356 | |
| Age, Continuous | Years | 55.2 (SD 4.17) | 54.9 (SD 4.72) | 54.2 (SD 4.78) | 54.0 (SD 5.18) | 54.6 (SD 4.73) |
| Sex: Female, Male: Female | Participants | 90 | 87 | 89 | 90 | 356 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 0 | 1 | 2 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 | 9 | 9 | 9 | 31 |
| Race (NIH/OMB): White | Participants | 84 | 78 | 79 | 79 | 320 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE, measured over Up to 21 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome counts participants with adverse events and serious adverse events and also classifies adverse events as mild, moderate, or severe. The timeframe is up to 21 weeks, and the stated unit is participants. An adverse event is defined broadly as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related. The record’s definition includes unfavorable signs, symptoms, diseases, and abnormal laboratory findings. A serious adverse event is defined by consequences such as death, a life-threatening event, hospitalization or prolonged hospitalization, disability or incapacity, congenital anomaly or birth defect, or other medical significance. Severity was assessed by the investigator.
Counting affected participants is useful for describing how often safety events were recorded in each group. Reporting serious events separately distinguishes events meeting the registry’s seriousness criteria from the broader adverse-event category; severity classification provides another description of the event burden. These counts are descriptive unless accompanied by a specified comparative analysis. A participant count alone does not convey event timing, duration, recurrence, or causal attribution. The registry record does not report a single combined primary endpoint value, a prespecified contrast, or an inferential analysis for these categories. The endpoint therefore needs to be read as a collection of safety summaries rather than as one numerical test of treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results list serious adverse events affecting 2 participants in the placebo group, 0 in the GSK232802 25 mg group, 1 in the GSK232802 75 mg group, and 1 in the Premarin 0.3 mg group. They list other adverse events affecting 30, 24, 21, and 17 participants, respectively, in those same groups. The recorded deaths are 0 for each group. These are counts, not estimates of a comparative treatment effect. The record does not supply confidence intervals, hypothesis tests, or an adjusted analysis for these comparisons.
There is an important denominator irregularity in the posted safety data. The serious-event at-risk count for GSK232802 25 mg is recorded as 878, while the other-adverse-event at-risk count for that group is 87. The registry also lists overall enrollment as 356. The serious-event denominator is therefore not readily reconciled with the other posted counts or the enrollment figure. The registry record does not explain this discrepancy, so the serious-event count for that group should not be interpreted as a rate or directly compared using an assumed denominator. The sponsor’s own analysis takes precedence if it differs from a simple recalculation based on these posted summaries; no sponsor comparative analysis is reported in the available record.
The four serious-event terms listed in the record are pneumonia, abdominal pain, lower limb fracture, and nasal septum deviation, each shown as 1.1%. The registry record does not link these terms to a particular treatment group in the information available, and the percentages should not be assigned to a group or treated as comparative estimates. Counts of participants with serious events and listed event terms are different ways of describing safety information; they should not be added together, because the record does not establish whether a participant could contribute to more than one term.
The primary outcome includes event counts by severity, but the registry entries do not provide the mild, moderate, and severe counts. Nor do they give a single primary efficacy result for hot-flash frequency or severity. Although symptom outcomes are listed as secondary measures, their numerical results and comparative analyses are not reported in the registry record. Accordingly, the safety counts support only a descriptive reading of the recorded events, with particular caution about the 25 mg serious-event denominator. They do not establish that one group had a higher or lower underlying risk, and they do not answer the study’s symptom-reduction question on their own.
9. Statistical Methods Explained
The registry describes a randomized, double-blind, parallel-group design. Randomization is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. It does not guarantee identical groups in a particular trial, especially when event counts are sparse. Double masking is intended to reduce the influence of treatment knowledge on participant reporting and investigator assessment. The record does not report the procedures used to generate the random sequence, conceal assignments, or maintain masking, so those design features cannot be evaluated in detail.
What do participant counts tell us?
A count records how many participants met a stated event definition. For safety outcomes, it is important to distinguish the number affected from the number at risk. A count without a compatible denominator cannot be interpreted as a frequency or risk. Even when a denominator is available, differences in raw counts can reflect differences in group size as well as differences in the occurrence of events. A comparative analysis ordinarily needs clearly defined groups, compatible denominators, and a stated statistical method. The record presents group counts but does not report a comparative method for the primary safety categories.
Here the denominator issue is especially relevant because the serious-event at-risk count listed for GSK232802 25 mg is 878, whereas the corresponding other-adverse-event at-risk count is 87 and overall enrollment is 356. The record does not resolve this discrepancy. It would be inappropriate to silently replace the listed value, presume a typographical error, or calculate a risk using a guessed denominator. The count of 0 serious events is still a posted count, but its interpretation alongside that at-risk value remains limited.
Why do confidence intervals matter?
In general, a confidence interval describes the range of values reasonably compatible with the data and a specified statistical model. It communicates precision as well as direction and can show when sparse event data leave substantial uncertainty. A point estimate alone cannot show how much uncertainty surrounds a comparison. The registry entries do not include confidence intervals for the primary safety counts, nor do they provide a comparative effect estimate to which an interval could be attached. General principles about intervals therefore do not imply a particular degree of precision for these results.
How should sparse events be read?
In general, when events are uncommon, small changes in counts can have a large influence on a relative comparison, while estimates may be imprecise. A count of zero in a group means that no affected participants were recorded for that category in the posted data; it does not prove that the underlying risk is zero. Serious-event counts in the posted groups are low, and no formal comparative result is reported. The available information is therefore more suitable for describing recorded events than for ranking treatments by safety.
What do the planning assumptions represent?
The registry includes sample-size planning illustrations 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 a stated fraction of the observed effect. Such illustrations are planning calculations, not observed trial findings and not observed power. They do not establish the trial’s original design rationale. The registry explicitly distinguishes these illustrations from the trial’s own design. No trial-specific sample-size justification or prospective statistical plan is reported in the registry record.
The record identifies a binary outcome type and describes its meaning as participants with an event, but it does not report the inferential model, any adjustment for covariates, or how repeated events were handled. A participant-level count and an event-level count are not interchangeable: one participant may experience more than one event, while the primary measure is stated in participants. The posted safety summaries do not give enough detail to reconstruct event-level analyses or verify a model. Any recalculation from posted summary statistics would be unadjusted; where a discrepancy exists, the sponsor’s own analysis takes precedence. No sponsor analysis resolving the denominator issue is reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including change in vasomotor symptom frequency and severity, responder thresholds at week 12, menopause quality of life, sleep, vulvar vaginal atrophy symptoms, and fatigue. It reports 48 outcome measures and 6 analyses. Evaluating multiple outcomes and timepoints can increase the chance of finding an apparently notable result by chance if many tests are conducted. In general, statistical plans may address this through a prespecified hierarchy, adjustment, or a clear distinction between confirmatory and exploratory analyses. The registry record does not report whether any multiplicity procedure was used, which comparisons were prioritized, or whether the secondary outcomes were intended as confirmatory.
Missing-data methods are not reported in the registry record. The registry entries do not explain how participants who discontinued, missed visits, or had incomplete symptom diaries were handled, or whether imputation was used. Those details matter particularly for repeated symptom measures and change-from-baseline outcomes, because the set of observed participants may differ across visits. The record also does not report outcome-specific denominators or the amount and pattern of missing data.
The safety population is defined as all randomized participants who received at least one dose of investigational product. The registry record does not state whether efficacy analyses used this population, all randomized participants, or another set. It also does not describe analysis populations for individual secondary outcomes. Randomization protects the original group comparison, but excluding participants after randomization can affect comparability; the extent of any such issue cannot be assessed without population definitions and participant flow information. No participant-flow counts or analysis-population details beyond the safety definition are reported in the registry 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 |
|---|---|---|---|
| Placebo | 2 | 90 | 2.2% |
| GSK232802 25 mg | 0 | 878 | 0.0% |
| GSK232802 75 mg | 1 | 88 | 1.1% |
| Premarin 0.3 mg | 1 | 90 | 1.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 90 |
| GSK232802 25 mg | 0 of 87 |
| GSK232802 75 mg | 0 of 88 |
| Premarin 0.3 mg | 0 of 90 |
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 | 30 of 90 |
| GSK232802 25 mg | 24 of 87 |
| GSK232802 75 mg | 21 of 88 |
| Premarin 0.3 mg | 17 of 90 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | GSK232802 25 mg | GSK232802 75 mg | Premarin 0.3 mg |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 1 of 90 | 0 of 878 | 0 of 88 | 0 of 90 |
| Pneumonia | Infections and infestations | 0 of 90 | 0 of 878 | 1 of 88 | 0 of 90 |
| Lower limb fracture | Injury, poisoning and procedural complications | 0 of 90 | 0 of 878 | 0 of 88 | 1 of 90 |
| Nasal septum deviation | Respiratory, thoracic and mediastinal disorders | 1 of 90 | 0 of 878 | 0 of 88 | 0 of 90 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | GSK232802 25 mg | GSK232802 75 mg | Premarin 0.3 mg |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 14 of 90 | 8 of 87 | 7 of 88 | 3 of 90 |
| Nausea | Gastrointestinal disorders | 5 of 90 | 6 of 87 | 5 of 88 | 6 of 90 |
| Nasopharyngitis | Infections and infestations | 8 of 90 | 3 of 87 | 5 of 88 | 5 of 90 |
| Upper respiratory tract infection | Infections and infestations | 5 of 90 | 4 of 87 | 3 of 88 | 3 of 90 |
| Diarrhoea | Gastrointestinal disorders | 2 of 90 | 6 of 87 | 4 of 88 | 3 of 90 |
Serious events with the highest arm-level rate: pneumonia (1.1%), abdominal pain (1.1%), lower limb fracture (1.1%), nasal septum deviation (1.1%).
The serious adverse-event counts are 2 for placebo, 0 for GSK232802 25 mg, 1 for GSK232802 75 mg, and 1 for Premarin 0.3 mg. The recorded death count is 0 in each group. These figures describe participants recorded as affected in the posted safety summaries; they do not by themselves establish whether events were caused by treatment. The registry’s definition of an adverse event explicitly does not require a judgment that the event is related to the medicinal product.
Interpret the serious-event figures with particular caution because the at-risk count for GSK232802 25 mg is listed as 878, while its other-adverse-event at-risk count is 87 and overall enrollment is 356. The record does not explain the inconsistency. As a result, a rate or comparative risk using the serious-event denominator for this group cannot be confidently interpreted from the posted information. The record lists pneumonia, abdominal pain, lower limb fracture, and nasal septum deviation as serious-event terms, each at 1.1%, but does not identify their group assignment in the registry entries. These terms should not be taken as evidence of a treatment-specific pattern. The serious-event counts are sparse descriptive observations, not a standalone basis for a comparative safety conclusion.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study compared placebo, two doses of GSK232802, and Premarin in a randomized, double-blind, parallel-group design, and that the primary outcome concerned adverse-event counts and severity. It also records group-level counts of participants affected by serious and other adverse events, as well as deaths. This is useful descriptive information about the safety events recorded during the stated follow-up period.
These registry entries do not establish a comparative safety effect. The record does not provide a formal primary-outcome test, an effect estimate, or uncertainty intervals. The unusual serious-event denominator listed for GSK232802 25 mg further limits direct comparison of serious-event frequency. A zero count in a group is not proof of no risk, and a difference between raw group counts should not be interpreted as a treatment effect without suitable denominators and a specified analysis.
The study’s stated broader purpose includes assessing hot-flash frequency and severity, and related symptom measures appear among the secondary outcomes. The numerical results for those efficacy outcomes are not reported in the registry entries. No conclusion about symptom reduction, quality of life, sleep, or the other secondary measures can therefore be drawn from the available results. Nor does the record report enough information to assess whether the statistical plan controlled multiplicity or how missing outcome data were handled.
In general, trial results are interpreted in light of the design, outcome definitions, analysis population, uncertainty, and completeness of follow-up. For this record, those considerations support a restrained reading: the posted safety counts describe observed events, while comparative safety and efficacy conclusions require analyses and details not reported in the registry record. The sample-size illustrations are planning exercises based on observed effects, not evidence of the precision achieved in this trial or of observed power.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry record puts several kinds of questions side by side. The broad study purpose concerns reducing vasomotor symptoms, while the stated primary outcome is a safety count. Secondary outcomes address symptom change and patient-reported measures at different visits. Keeping these roles distinct prevents a safety endpoint from being mistaken for the study’s efficacy question, and prevents listed secondary outcomes from being treated as demonstrated findings when their numerical results are not reported.
The record also illustrates why denominators and data checks are essential. The serious-event at-risk count for GSK232802 25 mg is recorded as 878, while the other-adverse-event at-risk count for that group is 87 and the enrollment figure is 356. Without clarification, even an apparently simple comparison of safety frequencies is compromised. Clear reporting of analysis populations, denominators, and outcome definitions is necessary before readers can interpret group differences or reproduce a calculation.
Finally, the many listed outcomes and timepoints raise general questions about multiplicity, missing data, and prespecification. The record does not report how those issues were handled. The presence of sample-size illustrations based on observed effects also makes it important to distinguish planning calculations from trial design and observed evidence. These are broadly useful statistical lessons: a randomized design does not remove the need for transparent analysis methods, coherent denominators, and uncertainty estimates. In this case, the registry entries allow a focused description of design and recorded safety counts, but do not support a full assessment of comparative effects.
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 available registry information does not report a complete statistical analysis plan, including the primary comparison, inferential method, covariate adjustment, or handling of repeated events. The primary endpoint combines several safety categories, yet the registry entries do not give the mild, moderate, and severe counts or a single summary comparison. Consequently, the primary outcome cannot be reconstructed as a complete analysis from the available record.
There is a notable internal denominator inconsistency: the serious-event at-risk count for GSK232802 25 mg is 878, while the other-adverse-event at-risk count is 87, and overall enrollment is 356. The record does not explain which value should be used. This makes the serious-event summary for that group difficult to compare with the other groups. The listed serious-event terms and percentages are not tied to groups in the available information, limiting interpretation of their distribution.
The record does not report confidence intervals or comparative estimates for safety outcomes, and it does not provide numerical results for the listed efficacy outcomes. It also does not report the multiplicity strategy, missing-data approach, efficacy analysis population, participant flow, detailed randomization procedures, or the specific roles included in double masking. The safety population definition alone cannot fill those gaps. The sample-size assumptions are explicitly described as planning illustrations based on observed effects rather than the trial’s own design rationale. These limitations constrain both reproducibility and the strength of any conclusion that can be drawn from the posted record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Treatment Of Hot Flashes/Flushes In Postmenopausal Women (WARM Study) — NCT00604825.
- Registry record last updated 2017-10-03; status last verified 2017-09.
- Results first posted 2017-10-03.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
The WARM Study is recorded as a completed, phase 2, randomized, double-blind, parallel-group, multicenter trial with enrollment of 356. It evaluated placebo, GSK232802 25 mg, GSK232802 75 mg, and Premarin 0.3 mg in healthy postmenopausal women with moderate to extremely severe vasomotor symptoms. The official title describes oral GSK232802 monotherapy for 12 weeks.
The stated primary outcome counts participants with adverse events and serious adverse events and classifies adverse-event severity, with a timeframe up to 21 weeks. Serious-event counts were 2, 0, 1, and 1 across the listed groups; other adverse-event counts were 30, 24, 21, and 17. Deaths were recorded as 0 in each group. The serious-event denominator for GSK232802 25 mg is listed as 878, an unexplained inconsistency with the other posted figures. Numerical efficacy results, comparative analyses, and key statistical procedures are not reported in the registry record.