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 Understanding Experimentally Induced Hot Flushes (NCT00455689), a non-randomized phase 4 study. The primary outcome is Percent Change in Objective Sleep Efficiency.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00455689 |
| Phase | Phase 4 |
| Condition | Hot Flashes |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes study subjects receiving leuprolide acetate. Enrollment was 20. The record does not report further participant characteristics, such as age or menopausal status, so the population cannot be characterized more specifically from this information.
Intervention
Participants received leuprolide acetate as a 3.75 mg intramuscular injection. The study summary describes the intervention as a way to induce hot flashes temporarily and to examine their impact on sleep, mood, and well-being.
Comparator
There was no randomized or untreated comparator. The registry describes groups according to whether subjects developed hot flashes after receiving leuprolide acetate. This is a grouping by what happened after treatment, not a comparison assigned in advance.
Primary question
The primary endpoint concerns percent change in objective sleep efficiency from baseline, before intervention, to 4 weeks after intervention. The registry specifies that sleep efficiency was measured with actigraphy and reported as a median with an inter-quartile range. It does not report the endpoint results or an analysis comparing the hot-flash groups.
3. Trial Design
The registry classifies the study as phase 4, non-randomized, unmasked, and single-group. Enrollment was 20, and the study status is completed. The recorded study dates run from 2005-11-28 to primary completion on 2007-07-24. Massachusetts General Hospital is listed as the sponsor.
All subjects in the described groups received leuprolide acetate, specified as a 3.75 mg intramuscular injection. The groups are defined by whether subjects developed hot flashes after receiving it. Because group membership depends on a post-intervention response, these groups are not equivalent to treatment arms assigned by randomization. In particular, the group that did not develop hot flashes is not an untreated control group.
The study summary says investigators intended to examine hot flashes’ impact on sleep, mood, and well-being, using questionnaires to evaluate changes in sleep and mood. The primary endpoint instead records objective sleep efficiency using actigraphy, averaged over 2 consecutive nights at baseline and again 4 weeks after intervention. Change in subjective sleep quality is listed as a secondary outcome.
The registry record does not report a randomized allocation process, masking procedures, a comparator intervention, or a statistical analysis plan. Those absences matter when interpreting group differences: the design can describe changes and associations in the studied participants, but the group definitions do not by themselves isolate the effect of hot flashes from other differences between subjects.
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 | Developed Hot Flashes | Did Not Develop Hot Flashes |
|---|---|---|
| STARTED | 14 | 6 |
| COMPLETED | 14 | 6 |
| NOT COMPLETED | 0 | 0 |
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 | Developed Hot Flashes | Did Not Develop Hot Flashes | Total |
|---|---|---|---|---|
| Participants analysed | 14 | 6 | 20 | |
| Age, Continuous | years | 32.8 (SD 9.0) | 25.5 (SD 6.7) | 30.6 (SD 8.9) |
| Sex: Female, Male: Female | Participants | 14 | 6 | 20 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Non-Hispanic White | Participants | 8 | 3 | 11 |
| Race/Ethnicity, Customized: Hispanic or African-American | Participants | 6 | 3 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change in Objective Sleep Efficiency, measured over baseline (before receiving intervention) and 4 weeks after receiving intervention.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | percent change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is percent change in objective sleep efficiency. Sleep efficiency is defined in the registry as the percent of time spent asleep between bedtime and wake time. It was measured using actigraphy and averaged over 2 consecutive nights before intervention and over 2 consecutive nights 4 weeks after intervention. The endpoint therefore focuses on sleep measured by a device rather than relying solely on a participant’s impression of sleep.
Using the same measurement approach at baseline and follow-up allows the study to describe within-participant change over that interval. A median and inter-quartile range are specified, which describe the center and spread of the endpoint without assuming that a mean adequately represents its distribution. These summaries can be useful when values are skewed or when a small number of observations could strongly affect the mean. This is a general statistical rationale, not evidence about the actual distribution in this study.
The registry does not report the median percent change, its inter-quartile range, or a test of change. It also does not report how missing actigraphy measurements, if any, were handled. Consequently, the endpoint definition is available, but the size and precision of the observed change are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available registry information describes the question and measurement approach, but not the primary outcome result. No median percent change in objective sleep efficiency, inter-quartile range, confidence interval, or inferential test is reported in the registry record. The record lists zero analyses. Accordingly, the direction, magnitude, and precision of the primary endpoint cannot be assessed from this record.
The study’s group descriptions require particular care. Subjects were categorized by whether they developed hot flashes after receiving leuprolide acetate. Since this status is determined after the intervention, the groups may differ in characteristics related to both hot flashes and sleep. A contrast between them would be an observational comparison within this study, not a randomized estimate of the effect of hot flashes. Differences could reflect factors other than hot flashes, and the registry record does not describe adjustment for such factors.
The primary endpoint is a before-and-after measure, with baseline before intervention and follow-up 4 weeks after intervention. A within-person change can describe how measured sleep efficiency changed over that interval. Without a comparator group that did not receive the intervention under comparable conditions, such a change alone cannot separate intervention-related change from time trends, measurement variability, or other influences. This is a general limitation of interpreting uncontrolled before-and-after data.
The secondary outcome listed is change in subjective sleep quality. The summary also describes questionnaires addressing sleep and mood, but no questionnaire results or mood endpoint results are reported in the registry record. There is no basis for judging whether subjective reports corresponded to actigraphy measurements.
Enrollment was 20. That number describes the study enrollment recorded in the registry; it does not establish how many participants contributed data to the primary endpoint or to any particular group. Group-specific denominators and endpoint analysis populations are not reported in the registry record. The absence of an analysis result means that claims about statistical significance, effect size, or consistency between groups are not supported by the record.
Thus, the registry supports a description of a completed, non-randomized study design and its planned sleep measurement, alongside limited adverse-event counts. It does not support a quantitative conclusion about the study’s primary sleep outcome.
9. Statistical Methods Explained
The registry record identifies a median and inter-quartile range for the primary endpoint. These are descriptive statistics. A median locates the middle of the observed values when arranged in order, while the inter-quartile range describes the spread of the central portion of those values. They can communicate a typical value and variability without requiring the endpoint to follow a normal distribution. That is a general explanation; the record does not report the actual median, inter-quartile range, or endpoint distribution for this study.
What does a confidence interval add?
A confidence interval is a range of values calculated from data to convey uncertainty around an estimate under a specified statistical procedure. A narrow interval generally indicates greater precision than a wide interval, while an interval that spans substantively different possibilities leaves more uncertainty about the effect’s size. An interval does not repair bias in the study design, and it does not make a non-randomized comparison causal. No confidence interval for the primary outcome is reported in the registry record.
Why does the grouping matter?
In a randomized comparison, assignment to groups is determined before outcomes occur, which can help balance measured and unmeasured characteristics on average. In this study, the registry defines the groups by whether hot flashes developed after leuprolide acetate. This is a post-intervention characteristic. People who do and do not develop hot flashes may differ in ways that also relate to sleep. A statistical comparison between these groups would therefore describe an association, subject to confounding, rather than a randomized treatment contrast. The registry record does not report an adjustment strategy or an analysis of group differences.
Similarly, comparing a participant’s baseline and follow-up sleep efficiency can describe change over time but does not, on its own, identify why that change occurred. Without a comparable group that did not receive the intervention, secular change, ordinary fluctuation, measurement error, and other concurrent influences remain possible explanations. This is a general point about uncontrolled before-and-after designs, not a claim about which explanation applies in this study.
Why can over-dispersion matter?
Over-dispersion occurs when observed variability in data is greater than a statistical model assumes. If a model underestimates variability, standard errors may be too small and intervals or tests may convey more certainty than the data warrant. Methods designed for over-dispersed outcomes can account for extra variability. The registry does not identify a count-based primary outcome or report a model for this endpoint, so over-dispersion is a general statistical concept rather than a documented feature of this study.
How should planning calculations be read?
Planning illustrations are hypothetical calculations about the size of a future study under stated assumptions; they are not outcomes from participants and are not observed power. The described illustration assumptions include a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The stated convention is that time-to-event illustrations give a total number of events, using the Schoenfeld approach, while other illustrations give participants per arm. These are planning conventions, not evidence that this trial used equal allocation or a randomized comparison. The registry record does not report the observed primary endpoint effect needed to evaluate such an illustration in context.
A sample-size calculation also depends on assumptions about the target effect, variability, allocation, and analysis method. If those assumptions do not resemble a future study, the resulting planning quantity may not be useful for it. Such a calculation does not establish that the completed study was adequately powered, and it cannot substitute for a reported estimate with uncertainty. The registry record does not report a sample-size justification for this study.
What can be inferred from the record?
The study is marked completed and includes an endpoint definition, but the registry lists zero analyses and does not report primary endpoint estimates or statistical tests. The registry record also does not report whether a model was fitted, whether covariates were considered, or how incomplete observations were treated. Without these details, readers cannot assess the analytic choices or reproduce an inferential result. The appropriate interpretation is therefore limited to the design and measurement information actually recorded, rather than conclusions about efficacy or statistical significance.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint of percent change in objective sleep efficiency and a secondary outcome of change in subjective sleep quality. The study summary also describes questionnaires intended to evaluate sleep and mood. The registry record does not report a multiplicity strategy, such as a prespecified hierarchy of tests or an adjustment for testing multiple outcomes. In general, examining multiple outcomes or analyses can increase the chance of at least one apparently unusual result, so a clear testing plan helps readers interpret inferential findings. No such findings are reported.
The record lists zero analyses. It does not report a missing-data method, the extent of missing endpoint data, or whether all enrolled subjects contributed to each outcome. The analysis population for the primary endpoint is not reported in the registry record. Enrollment was 20, but enrollment alone does not establish the number of observations available for analysis.
These omissions limit assessment of completeness and potential bias. If participants with unavailable measurements differed from those measured, an analysis restricted to observed values could misrepresent the study population; this is a general possibility, not a claim that missingness occurred. The registry record does not say whether missing values were imputed, whether sensitivity analyses were conducted, or what rules defined inclusion in an analysis. It also does not report an analysis plan that would clarify which outcome comparisons were intended. Therefore, neither multiplicity control nor the handling of missing observations can be evaluated from 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 |
|---|---|---|---|
| All Subjects | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Subjects | 0 of 20 |
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 |
|---|---|
| All Subjects | 13 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Subjects |
|---|---|---|
| Fatigue | General disorders | 3 of 20 |
| Headache | Nervous system disorders | 2 of 20 |
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | 2 of 20 |
| Acne | Skin and subcutaneous tissue disorders | 1 of 20 |
| Bloating | Gastrointestinal disorders | 1 of 20 |
| malodorous urine | Renal and urinary disorders | 1 of 20 |
| Irritability | Psychiatric disorders | 1 of 20 |
| Increased libido | General disorders | 1 of 20 |
| Edema | Vascular disorders | 1 of 20 |
For the all-subjects safety group, the registry lists 20 at risk for serious adverse events and 0 affected; it lists 20 at risk for other adverse events and 13 affected. Deaths are listed as 0. No serious adverse event terms are listed. These are registry counts, not estimates of comparative risk, because there is no untreated or randomized comparator described.
The zero serious adverse-event count means that no serious events are recorded as affecting subjects in this registry entry; it does not establish that the intervention has no serious risks. The count of 13 under other adverse events should not be read as a measure of severity or as a complete description of the events. The registry record does not list the other-event terms, their timing, duration, or relationship to the intervention. It also does not report a comparison with another group. The at-risk counts describe the recorded safety denominator, but do not establish whether safety follow-up was complete for every participant.
12. What the Result Does, and Does Not, Mean
This record documents a study designed to examine experimentally induced hot flashes in relation to sleep, mood, and well-being. It specifies a device-based primary sleep endpoint and a follow-up time point. Those details clarify what investigators intended to measure, but they are not outcome findings. The registry record does not report a primary endpoint estimate or an analysis result, so it cannot establish whether objective sleep efficiency changed or how large or precise any change was.
The groups are categorized by whether hot flashes developed after participants received leuprolide acetate. They are not randomized treatment groups, and the group that did not develop hot flashes is not an untreated comparison. Any difference between these categories could be associated with factors that also influence sleep. The design therefore does not, by itself, establish that hot flashes caused a difference in sleep efficiency.
The listed secondary outcome, change in subjective sleep quality, has no reported result in the registry record. Although the study summary mentions questionnaires about sleep and mood, it does not provide those results. The record likewise does not provide enough information about missing data or analysis populations to determine how complete the outcome evidence is.
Safety entries record 0 serious adverse events among 20 at risk, 13 affected by other adverse events among 20 at risk, and 0 deaths. Those counts describe the registry entry, not comparative safety, and the other adverse-event terms are not reported. Overall, the record is informative about the design and intended measurements but insufficient for conclusions about the magnitude, precision, or causal meaning of sleep outcomes.
13. Why This Trial Matters Statistically
This study is statistically instructive because its group labels can sound like treatment arms even though they are defined by an outcome occurring after intervention. Distinguishing assigned groups from post-intervention subgroups is essential: the latter may differ for reasons related to the response used to define them. A contrast between the hot-flash groups would not have the same interpretation as a randomized comparison.
The record also illustrates the difference between a well-defined endpoint and a reported result. It states how objective sleep efficiency was measured, when it was measured, and which summary statistics were specified. Yet without the endpoint estimate, spread, and inferential analysis, readers cannot judge the size or precision of change. Measurement detail cannot substitute for results.
There is also a useful distinction between observed change and causal attribution. A baseline-to-follow-up comparison can describe what happened over time in the measured participants. Without a comparable control condition, it cannot isolate the intervention or hot flashes as the reason for that change. This remains true even if a future analysis reports a statistically precise association.
Finally, the registry record makes clear why transparency about analysis populations, missing data, and multiplicity matters. Those details help readers assess whether findings reflect the intended population and how uncertainty should be interpreted. Their absence limits what can be learned from the registry entry, rather than implying that a particular unreported method was or was not used.
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 study is non-randomized, unmasked, and recorded as single-group. Its hot-flash categories are based on whether hot flashes developed after intervention, so they do not create a like-for-like control comparison. The design cannot rule out differences between these post-intervention groups that could also relate to sleep.
The primary endpoint is defined as percent change in objective sleep efficiency, but the registry record does not report the median, inter-quartile range, confidence interval, test result, or group-specific estimates. It lists zero analyses. Results for the secondary outcome of subjective sleep quality are also not reported. This prevents evaluation of the magnitude and precision of the outcomes, and whether objective and subjective measures agreed.
Enrollment was 20, but group-specific sizes and endpoint analysis denominators are not reported in the registry record. Missingness, exclusions, follow-up completeness, and analysis-population definitions are also not reported. No statistical analysis plan, multiplicity approach, or sample-size justification is recorded. These gaps prevent assessment of analytic choices and the completeness of available outcome data.
The safety record provides counts but not event descriptions for other adverse events, timing, follow-up context, or comparative data. The registry entry therefore offers limited detail for judging the pattern of safety events. These limitations concern what the registry record reports; they do not establish whether additional procedures or analyses occurred outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Understanding Experimentally Induced Hot Flushes — NCT00455689.
- Registry record last updated 2018-09-18; status last verified 2018-08.
- Results first posted 2018-08-21.
- 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
NCT00455689, titled “Understanding Experimentally Induced Hot Flushes,” is recorded as a completed phase 4, non-randomized, unmasked, single-group study sponsored by Massachusetts General Hospital. Enrollment was 20. The study dates recorded are 2005-11-28 through primary completion on 2007-07-24.
Participants received leuprolide acetate as a 3.75 mg intramuscular injection. Groups were defined by whether subjects developed hot flashes after receiving it. The primary outcome was percent change in objective sleep efficiency, measured by actigraphy at baseline and 4 weeks after intervention, with a median and inter-quartile range specified. Change in subjective sleep quality is listed as a secondary outcome.
The registry lists zero analyses and does not report endpoint results. Safety entries list 0 serious adverse events, 13 affected by other adverse events, and 0 deaths. The record describes the study question and measurement methods, but does not provide results for judging the primary sleep outcome.