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 Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder (NCT00626340), a non-randomized phase 4 study. The primary outcome is Comparison of Cortical GABA Levels in 4 Groups of Subjects Using Estrogen Alone, Fluoxetine Alone, Estrogen and Fluoxetine Combined in Pre and Post 4.0T Magnetic Resonance Spectroscopy Sessions..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00626340 |
| Phase | Phase 4 |
| Condition | Menopause, Depression |
| Allocation | Non-Randomized |
| Design model | Factorial |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
Menopausal women between the ages of 40-70, including women diagnosed with major depressive disorder and non-depressed healthy controls. The registry reports 18 participants completed, but does not report how participants were distributed among the groups.
Intervention
Women with depression were assigned in the study record to estrogen alone, fluoxetine alone, or estrogen with fluoxetine. Non-depressed controls received estrogen. These descriptions identify the treatment groups; they do not establish that treatment allocation was randomized.
Comparator
The planned comparisons concern GABA levels before and after treatment within the groups, and levels across the four groups. Because allocation was non-randomized, the groups are not a like-for-like control comparison. The registry does not report an analyzed comparison.
Primary question
How do cortical GABA levels measured by magnetic resonance spectroscopy differ before and after treatment, and across the four groups? The study also describes planned correlations between cortical GABA and plasma GABA and neurosteroid levels, but those are not the listed primary endpoint.
The clinical question is framed around a biological measurement rather than a reported clinical outcome. The proposed scans were intended to measure cortical GABA, a neurotransmitter, using magnetic resonance spectroscopy. The registry also names progesterone, allopregnanolone, pregnenolone, and pregnenolone sulfate as neurosteroids to be measured, and describes correlating these and plasma GABA with cortical GABA. No numerical measurements, association estimates, or analyzed treatment comparisons are reported in the registry record. The record says the data were not analyzed, so it cannot answer whether the planned groups differed or whether levels changed over time.
3. Trial Design
This is a phase 4, non-randomized study classified in the registry as having a factorial model and no masking. It enrolled 18 participants and is listed as completed. The record describes four groups: menopausal women with major depressive disorder receiving estrogen alone, fluoxetine alone, or both treatments, and non-depressed menopausal women receiving estrogen. The arm descriptions specify women between the ages of 40-70.
The planned measurement schedule differed by group. Healthy controls were to have scans before and after 3 weeks of estrogen treatment. Women with depression were to have scans before and after 6 weeks of treatment with estrogen alone, estrogen with fluoxetine, or fluoxetine alone. The primary outcome description refers to pre and post 4.0T magnetic resonance spectroscopy sessions. The record does not report the number of participants in each group, details of treatment allocation, adherence, or the timing of individual measurements.
The non-randomized allocation matters when interpreting group comparisons: differences between groups may reflect pre-existing differences as well as treatment or diagnosis. The registry specifically flags that the arms are not a like-for-like control comparison. The factorial label does not make the design randomized, and the record does not describe a factorial analysis or the statistical model used.
The study began in 1999-07 and reached primary completion in 2008-07. Its primary outcome description says the study was conducted at Yale University, while the sponsor is listed as University of Pennsylvania. The registry states that University of Pennsylvania staff do not have access to the additional study data and that the data collected were not analyzed. The protocol, sample-size justification, analysis plan, and interim-analysis information 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.
Overall Study
| Stage | All Participants |
|---|---|
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: UPenn does not have access to the data collected for this study. We are only using the information entered in the protocol section for very basic details in the results section (i.e, number of participants completed). The original contact person for this protocol is not reachable.
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: As far as we know, data was never analyzed for this study. We only know that 18 participants completed.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 0 | |
| Sex: Female, Male: Female | — | |
| Sex: Female, Male: Male | — |
6. Primary Endpoint
The registry lists the primary outcome as Comparison of Cortical GABA Levels in 4 Groups of Subjects Using Estrogen Alone, Fluoxetine Alone, Estrogen and Fluoxetine Combined in Pre and Post 4.0T Magnetic Resonance Spectroscopy Sessions., measured over Healthy controls will undergo scans pre and post 3 weeks of estrogen treatment. Women with depression will undergo scans pre and post 6 weeks of treatment with estrogen alone, estrogen and fluoxetine, or fluoxetine alone.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the comparison of cortical GABA levels across four groups, measured in pre and post 4.0T magnetic resonance spectroscopy sessions. The planned groups differ by depression status and treatment: estrogen alone for healthy controls; and estrogen alone, fluoxetine alone, or the combination of estrogen and fluoxetine for women with depression. The schedule describes scans before and after 3 weeks of estrogen in controls and before and after 6 weeks of treatment in women with depression.
In general, a biological endpoint can help characterize a physiological change or difference relevant to a study’s research question. Repeated measurements before and after treatment can describe within-person change, while comparisons across groups can describe how those changes or levels vary by group. These are different questions, and interpreting a group difference as a treatment effect requires an appropriate design and analysis. Because allocation was non-randomized, group comparisons are not automatically protected against confounding.
The registry does not report the unit, measurement values, variability, or an analysis of this endpoint. It explicitly says the data were never analyzed to the best of the study contact’s knowledge. Consequently, the record identifies what was intended to be measured but does not report a result for the primary endpoint. The proposed plasma and neurosteroid measurements are described as correlates, not as reported endpoint findings.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record documents a completed study with 18 participants and a stated primary outcome focused on cortical GABA levels before and after treatment. It does not provide numerical endpoint results. The primary outcome description says that the data were not analyzed for the participants who completed the study, and that additional study data were unavailable to University of Pennsylvania staff. Therefore, there is no reported estimate of a change in GABA, no estimate of a difference among the four groups, and no inferential result to interpret.
This absence of results is not evidence that the groups had identical GABA levels or that there was no change. It means the registry does not report an analysis capable of establishing the direction, size, or precision of any difference. There are no reported means, medians, standard deviations, confidence intervals, test statistics, or p-values for the primary endpoint. No effect estimate can be assessed against its uncertainty, and the magnitude of any observed change cannot be characterized from this record.
The design also limits what a group contrast could establish, even if analyzed results were available. Allocation was non-randomized and the record says the arms are not a like-for-like control comparison. In general, non-randomized group differences may reflect characteristics other than the treatments being compared. Comparisons over time within a group would address a different question from comparisons between treatment groups; neither would by itself establish a causal treatment effect without suitable design and analysis assumptions.
The four treatment groups also do not share a single reported measurement schedule: control scans are described around 3 weeks of estrogen treatment, while scans for women with depression are described around 6 weeks of treatment. Thus, the endpoint description incorporates differences in diagnosis, treatment, and follow-up timing. The registry does not report an analysis that separates these factors, nor does it report adjustment for potential confounders.
The adverse-event record reports zero serious adverse events, zero other adverse events, and zero deaths among the listed group of all participants. This is a descriptive safety record, not an estimate of the primary GABA outcome. With no reported endpoint analysis, the central statistical conclusion is that the intended biological question remains unanswered by the registry results, rather than that a particular effect was found or ruled out.
9. Statistical Methods Explained
What does a before-and-after measurement describe?
In general, a before-and-after analysis compares measurements from the same participant at two time points. Pairing can account for stable differences between participants when estimating average change within a group. It does not, by itself, establish that treatment caused the change: changes over time may also reflect other influences, and an untreated or otherwise suitable comparison may be needed to address them. This record describes pre and post scans, but reports no individual measurements or analyzed within-group changes.
What is the distinction between within-group and between-group comparisons?
In general, a within-group comparison asks whether a group’s outcome differs across its measurement times. A between-group comparison asks whether outcomes or changes differ across groups. They are not interchangeable. A group can show a pre-post change without having a different change from another group. Conversely, a between-group contrast can reflect baseline differences as well as later differences. Here, the four groups differ in depression status and treatment, and the record states that allocation was non-randomized. It does not report a model that estimates or separates these contrasts.
Why does non-randomized allocation matter?
In general, random allocation can help balance measured and unmeasured characteristics across treatment groups, on average. Without randomization, treatment choice or group membership may be related to participant characteristics that also relate to the outcome. Statistical adjustment can sometimes address measured differences, but cannot guarantee removal of unmeasured confounding. The registry explicitly cautions that the arms are not a like-for-like control comparison. It does not report covariate adjustment, a causal analysis, or the details of allocation.
What does a confidence interval communicate?
In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision; a wider interval indicates less precision. It does not correct a biased design, and it does not establish that the model assumptions are appropriate. No confidence interval or endpoint estimate is reported in the registry record, so precision cannot be evaluated for the planned GABA comparisons.
What role would a statistical test play?
In general, a statistical test evaluates how compatible the observed data are with a specified null hypothesis under a chosen model. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. Interpretation should consider the estimate and its uncertainty, the design, and the analysis assumptions. The registry does not report a test, p-value, or statistical analysis for the primary outcome. It also does not report a prespecified statistical plan, so the planned test and model are not reported in the registry record.
How should the planning illustrations be read?
In general, a sample-size calculation describes how much information a future design might need to detect a specified effect under stated assumptions. It is a planning illustration, not an observed trial result and not observed power. The record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. They state that non-time-to-event illustrations express participants per arm, while time-to-event illustrations express total events. These assumptions do not establish that the completed study used those methods or had that design.
There is an important limitation on applying such illustrations to this record: the primary outcome description says the study data were not analyzed, while the planning description refers to an observed effect. The registry does not report an effect estimate from this study that could be checked or interpreted. Accordingly, a planning illustration based on an effect is not evidence that the study detected that effect, and it cannot substitute for an outcome analysis. The record does not report the original sample-size justification or intended power calculation.
Why is a single summary contrast not enough?
In general, a model needs to match the question and the structure of the data. Repeated measurements, multiple groups, and non-randomized assignment raise distinct analytic considerations. A single contrast could obscure whether a finding concerns starting levels, change over time, or differences in change. If measurements have unequal schedules or missing observations, the chosen approach also affects interpretation. The registry does not report the participant-level data, missingness, model specification, or estimates required to assess these issues. The factorial classification alone does not establish which terms were included in an analysis.
All of these statistical concepts are general explanations. The registry record does not provide analyzed outcome data with which to apply them to the study’s primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The study describes several groups and multiple planned biological measurements, including cortical GABA, plasma GABA, and neurosteroids. Multiple comparisons can increase the chance of finding an apparently notable result when many hypotheses are tested. In general, an analysis plan may specify a primary contrast or a method for controlling multiplicity, but the registry does not report such a plan, a multiplicity adjustment, or analyses of secondary measurements. The record identifies one primary outcome measure and zero analyses.
Missing-data handling is also not reported in the registry record. The record says 18 participants completed, but does not provide participant-level follow-up, the number with usable scans, exclusions, or reasons for unavailable measurements. A completion count alone does not establish that every planned measurement was collected or included in an analysis. The registry says the data were not analyzed, so it does not report an analysis population or a method for handling missing outcomes.
In general, analysis populations should be defined in relation to the study design and the question being answered. For example, an analysis may aim to include all participants assigned or enrolled, or may use only those with particular measurements; each choice has implications. The record does not state which population would have been used, nor does it describe intention-to-treat, per-protocol, or other analysis populations.
These omissions mean that the robustness of any treatment comparison, correction for multiple testing, and potential influence of missing measurements cannot be assessed from the registry record. No additional analysis should be inferred from the completion status or from the stated endpoint.
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 Participants | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Participants | 0 of 18 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Participants | 0 of 18 |
The adverse-event record lists all participants as the group at risk. It reports zero serious adverse events, zero other adverse events, and zero deaths. The primary outcome description also states that no adverse events occurred. These figures are descriptive entries in the registry record; they do not constitute a comparative safety analysis across the treatment groups.
The record does not report adverse-event counts by treatment arm, event definitions, surveillance procedures, or the period during which events were collected. It therefore does not support comparisons of safety between estrogen, fluoxetine, and combined treatment, or between treated participants and controls. The registry’s summary of zero events should be read as what was recorded, not as proof that an event could not occur or that risk was absent. It also does not address the primary endpoint, which concerns cortical GABA measurements.
In general, event counts are most interpretable when the population under observation, follow-up period, ascertainment method, and group denominators are clearly described. Those details are not reported in the registry record for these adverse-event figures. The listed counts should therefore be presented as registry-reported observations, with the limitations of the available safety information kept explicit.
12. What the Result Does, and Does Not, Mean
The record establishes that a study of menopausal women with and without major depressive disorder was completed and that its primary research question concerned cortical GABA measurements before and after treatment. It records 18 participants completing and describes estrogen, fluoxetine, and combined treatment groups, along with non-depressed controls receiving estrogen. It also reports zero serious adverse events, zero other adverse events, and zero deaths in the all-participant group.
It does not establish whether cortical GABA levels changed, whether levels differed among groups, or whether any change was associated with treatment. No endpoint estimates or uncertainty measures are reported, and the primary outcome description says the data were not analyzed. This absence of analysis cannot be interpreted as a null finding. It is not evidence that the treatments had no effect, nor is it evidence of a difference.
The non-randomized design further constrains interpretation of any group contrast. Differences among groups could reflect diagnosis, treatment, baseline characteristics, or other factors. The listed factorial model does not resolve that issue, and the registry does not describe an analysis that accounts for it. The different planned treatment durations in controls and depressed participants also mean that a simple group comparison could mix differences in population, treatment, and timing.
In general, a treatment-effect claim requires a suitable comparison and a clearly reported analysis, including estimates and uncertainty. Those elements are absent from this record. The study’s planned biological measurements may have been intended to characterize relationships among cortical GABA, plasma GABA, and neurosteroids, but no correlations or other findings are reported. The sound interpretation is therefore limited: the registry documents the study’s question, design features, completion, and recorded adverse-event counts, but does not report analyzed results that answer the primary question.
13. Why This Trial Matters Statistically
This study is statistically notable because its record distinguishes study completion from availability of analyzed results. A completed study and a stated primary endpoint do not by themselves produce an interpretable estimate. Here, the registry reports 18 participants completing but also says the data were not analyzed and that the sponsor’s staff lacked access to additional study data. That makes the absence of a result central to interpretation, rather than a minor reporting detail.
The design also illustrates why labels and comparisons need careful reading. The study is classified as factorial, but allocation is non-randomized, and the registry warns that the arms are not a like-for-like control comparison. A design label does not replace details about assignment, the estimand, or the analysis. The four groups differ by depression status and treatment, while the described scanning schedules differ between controls and women with depression. These distinctions shape what a valid contrast could mean.
More broadly, the study highlights the difference between a biological research question and an answer supported by data analysis. Magnetic resonance spectroscopy measurements and neurosteroid correlations were planned, but no estimates, uncertainty measures, or statistical tests are reported. Without those results, readers cannot assess magnitude, precision, or compatibility with competing explanations. Statistical transparency includes reporting when planned data were not analyzed, so that a stated objective is not mistaken for an established finding.
The record is therefore useful for understanding the limits of the available evidence. It documents a completed, non-randomized investigation and its intended measurements, while making clear that the primary outcome remains unevaluated in the registry results.
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 most direct limitation is the absence of analyzed primary outcome data. The registry states that the data for the 18 participants were not analyzed, and that additional study data were not accessible to University of Pennsylvania staff. It reports no GABA measurements, group estimates, changes, confidence intervals, or statistical tests. Thus, the primary research question cannot be answered from the record.
Important design details are also unavailable. The record does not report participant counts within each group, how treatment allocation occurred, treatment adherence, baseline characteristics, or exclusions. Although the study is classified as non-randomized and factorial, the registry does not describe a statistical model or a plan for comparing groups. The listed arms should not be treated as randomized or directly exchangeable controls.
The planned groups differed in diagnosis and treatment, and the stated schedules differed in duration: 3 weeks for healthy controls and 6 weeks for women with depression. The registry does not report how these differences were addressed analytically. The primary endpoint’s unit and dispersion are unspecified, and the record does not report missing-measurement handling, analysis populations, or multiplicity procedures.
The safety record is limited to aggregate counts for all participants, without arm-specific event information or further details of ascertainment and follow-up. Finally, although planning assumptions are described, the original sample-size justification and the statistical plan are not reported in the registry record. These limitations prevent assessment of the precision, validity, or reproducibility of a treatment comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder — NCT00626340.
- Registry record last updated 2017-06-01; status last verified 2017-05.
- Results first posted 2017-06-01.
- 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 a completed phase 4, non-randomized study with no masking and a factorial model classification. It enrolled 18 participants, and the primary outcome description says 18 completed. The study planned pre and post 4.0T magnetic resonance spectroscopy measurements of cortical GABA in four groups of menopausal women with and without major depressive disorder. Controls were to receive estrogen; women with depression were to receive estrogen, fluoxetine, or both.
The registry reports that outcome data were not analyzed and that additional study data were unavailable to University of Pennsylvania staff. No primary endpoint estimates or inferential results are reported. The adverse-event record lists zero serious adverse events, zero other adverse events, and zero deaths among all participants. The central statistical limitation is therefore not an inconclusive estimate, but the absence of a reported analysis of the intended outcome.