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 Open-Label Study of Geodon in Non-Rapid Cycling Bipolar II Patients With Major Depression (NCT00237666), a na phase 4 study. The primary outcome is The Primary Efficacy Endpoint is the Comparison of Baseline and Week 8 Endpoint in the 17-item HAM-D Total Scores.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00237666 |
| Phase | Phase 4 |
| Condition | Bipolar II Disorder, Major Depressive Episode |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The Medical Research Network |
| Results posted | Yes |
2. Clinical Question
Population
Participants had Bipolar II disorder and were experiencing a major depressive episode. The study focused on non-rapid-cycling Bipolar II patients. The registry lists an enrollment of 30 and describes the per-protocol analysis population as 30 randomized subjects. It also notes that 6 participants dropped out before completion.
Intervention
The intervention was ziprasidone monotherapy, described as flexible-dose treatment at 20-60 mg BID. The study was open-label, so masking is listed as none. The registry's stated purpose was to evaluate antidepressant effectiveness in this clinical population; that purpose is not itself evidence of an observed benefit.
Comparator
There was no separate control group in this single-group study. The primary endpoint compares the baseline HAM-D total score with the Week 8 endpoint score, using last observation carried forward for participants who dropped out before completion. This is a within-participant comparison over time, not a comparison between treatment groups.
Primary question
The primary question was whether the 17-item HAM-D total score changed from baseline to Week 8 among participants receiving ziprasidone. The endpoint description defines the score and its direction, but the baseline and Week 8 summary results are not reported in the registry record. The size and precision of any observed change therefore cannot be assessed from the registry information available.
3. Trial Design
This was a Phase 4, open-label, flexible-dose, single-group study of ziprasidone in non-rapid-cycling Bipolar II patients with a major depressive episode. The registry lists the study as completed and identifies The Medical Research Network as sponsor. The recorded study start is 2005-02 and the primary completion date is 2008-02.
There was no parallel control arm: allocation is listed as not applicable, masking as none, and the study model as single group. The intervention description specifies ziprasidone monotherapy at 20-60 mg BID. Thus, the primary comparison is between participants' baseline and Week 8 HAM-D scores rather than between outcomes in separate treatment groups. Changes over time in a single group cannot distinguish a treatment-associated change from other influences, such as the course of symptoms or expectations in an open-label study.
The registry lists enrollment of 30. Its primary-outcome description says that the per-protocol analysis included 30 randomized subjects, and that Week 8 data or last observation carried forward were used for the 6 participants who dropped out before completion. The record does not explain the apparent distinction between the single-group design and its use of the phrase “randomized subjects”; a randomized comparison is not described.
The study also lists six secondary outcomes: changes in anxiety, depression, clinical global severity, and quality of life measures, along with a clinical global improvement category. These outcomes broaden the measures considered, but their numerical results are not reported in the registry record. A detailed protocol, recruitment process, eligibility criteria, dose-adjustment rules, and statistical analysis plan 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: The planned and actual study population was 30 patients, 18 years of age or older, who met DSM-IV criteria for bipolar II disorder with a history of at least one hypomanic episode.
Overall Study
| Stage | Ziprasidone |
|---|---|
| STARTED | 30 |
| COMPLETED | 24 |
| NOT COMPLETED | 6 |
Analysis population for the primary outcome, as defined in the registry: Per protocol, the number of participants for analysis was 30 randomized subjects; data analyzed at Week 8 or Last Observation Carried Forward for the 6 subjects who dropped out before completion.
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 | Ziprasidone |
|---|---|---|
| Participants analysed | 30 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 30 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age Continuous | years | 38.61 (SD 13.34) |
| Sex: Female, Male: Female | Participants | 21 |
| Sex: Female, Male: Male | Participants | 9 |
| Region of Enrollment: United States | participants | 30 |
6. Primary Endpoint
The registry lists the primary outcome as The Primary Efficacy Endpoint is the Comparison of Baseline and Week 8 Endpoint in the 17-item HAM-D Total Scores, measured over Week 8.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Scores on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the comparison of baseline and Week 8 scores on the 17-item Hamilton Depression Rating Scale (HAM-D). The registry describes HAM-D as a measure of depression symptoms, with possible total scores ranging from 0-54; higher scores indicate greater symptom severity. A change in a continuous score can describe how the measured symptom burden differs over time, while retaining more gradation than a simple improved/not-improved classification.
Using the same scale at baseline and follow-up makes it possible to describe within-participant change. In a general statistical sense, a mean change summarizes the average direction and magnitude of change across the analysis population. Its interpretation depends on the actual baseline and follow-up values, the variability of individual scores, and the number of participants contributing information. Those result values and their uncertainty are not reported in the registry record, so the mean change and its precision cannot be evaluated.
The registry labels the primary measure as a mean and identifies standard deviation as its dispersion measure. The population description specifies a per-protocol analysis and states that Week 8 data or last observation carried forward were used for the 6 participants who dropped out before completion. The record does not report the actual mean, standard deviation, or a confidence interval for the endpoint. The score's scale and direction explain what a result would represent, but do not establish whether or how much scores changed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a clear primary measurement target: change in the 17-item HAM-D total score from baseline to Week 8. However, it does not report the baseline score, Week 8 score, mean change, standard deviation, confidence interval, or significance test for that outcome. Consequently, the magnitude, direction, and statistical precision of the primary result are not reported in the registry record. No conclusion about the observed symptom-score change can be drawn from the endpoint description alone.
The study's single-group structure is central to interpretation. A baseline-to-follow-up comparison can describe change among participants who received ziprasidone, but there is no concurrent control group against which to compare that change. General influences over time, changes in care, natural symptom fluctuation, and expectations in an open-label study may also affect measurements. Without a control comparison, the registry record cannot isolate the contribution of the intervention to any change.
The per-protocol description says that the analysis involved 30 randomized subjects and that Week 8 data or last observation carried forward were used for the 6 participants who dropped out before completion. The implications of excluding or retaining participants depend on the analysis details and the reasons for missing observations. Those details are not reported in the registry record. In particular, the registry does not state whether the primary analysis included every enrolled participant as described, how the per-protocol population was defined, or whether sensitivity analyses were performed.
There are six listed secondary outcomes in addition to the primary endpoint. Their results are not reported in the registry record, and no multiplicity procedure is described. When a study examines multiple outcomes, the chance of finding at least one apparently notable result can be affected by how many comparisons are made and whether the analysis accounts for them. Without the outcome estimates and analysis details, neither the secondary findings nor their relationship to the primary endpoint can be assessed.
The record gives limited safety counts: one participant is recorded as having a serious adverse event, and 20 as having other adverse events, each among 30 at risk. White Blood Cell Count Decreased is listed as a top serious term at 3.3%. These entries do not provide event-level descriptions, timing, duration, or a comparison group. They should be read as registry-reported counts and terms, not as a comparative estimate of risk.
Overall, the registry supplies the design, endpoint definition, and some safety counts, but not the efficacy estimates needed to quantify the primary result. A completed status indicates that the study is listed as completed; it does not substitute for outcome values or establish the direction or reliability of an effect.
9. Statistical Methods Explained
The registry identifies a continuous primary measure: the mean HAM-D total score, with standard deviation as the stated measure of dispersion. For a continuous outcome, the mean describes the arithmetic average score in the analysis population. The standard deviation describes how spread out participants' scores are around that average. These answer different questions: the mean locates the group average, while the standard deviation describes variation among observations. Neither quantity is reported for the primary result in the registry record.
What does a baseline-to-follow-up comparison estimate?
A within-participant comparison uses repeated measurements from the same participants. The primary endpoint is framed as a comparison of baseline and Week 8 HAM-D total scores. A mean change would summarize the average difference between those measurements for the analysis population. This is not the same estimand as a difference between two independently assigned treatment groups. A within-participant comparison can account for each participant's starting score when describing change, but it does not provide the counterfactual comparison needed to determine what would have happened over the same period without the intervention.
In general, uncertainty around a mean estimate can be conveyed with a confidence interval. A confidence interval gives a range of values compatible with the data and the method used to construct it. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone resolves design limitations such as the absence of a control group. No confidence interval is reported for the primary outcome in the registry record, so its precision cannot be judged.
Why does a single-group design matter?
In this study, the registry identifies a single-group model and no masking. Participants and study personnel therefore were not masked to the intervention according to the registry entry. General methodological concerns in an open-label study include the possibility that expectations or awareness of treatment affect reported symptoms, assessments, or decisions during follow-up. The degree to which any such influence occurred is not reported in the registry record. More importantly, without a concurrent control group, a change from baseline cannot by itself separate intervention effects from time-related changes or other influences.
Allocation is listed as not applicable, consistent with the single-group model. The primary outcome description nevertheless uses the phrase “30 randomized subjects.” The record does not explain that wording. It does not describe a randomized treatment allocation or an arm-to-arm comparison, so the study should not be interpreted as a randomized controlled comparison on the basis of that phrase.
How should the missing observations be understood?
The registry states that Week 8 data or last observation carried forward were used for the 6 participants who dropped out before completion. Last observation carried forward is a method that substitutes a participant's last recorded value for a later measurement that is missing. As a general method, it makes an assumption about what the unobserved outcome would have been after dropout. If symptoms would have continued to change, remained stable, or changed differently after the last observation, carrying the last value forward may not represent the unobserved Week 8 score. The direction and size of any resulting bias depend on the missingness process and the underlying outcomes.
The registry does not report the dropout timing, reasons, last observed scores, or assumptions used to justify this approach. It also does not report alternative analyses to examine how conclusions might change under different assumptions about missing data. Therefore, the robustness of the primary analysis to missing observations cannot be assessed from the registry record.
What is known about multiplicity?
The registry lists 7 outcome measures: the primary HAM-D endpoint and six secondary outcomes. In general, testing multiple outcomes raises a multiplicity issue because the opportunity to observe a low p-value by chance can increase when many hypotheses are examined. Statistical approaches may control or otherwise address this issue, but the choice depends on the study's objectives and prespecified plan. The registry record does not report whether any multiplicity adjustment was planned or used, nor does it provide the outcome-level estimates or tests needed to assess the issue.
The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such a planning exercise is distinct from the design of this single-group study and is not evidence of observed power. The registry does not report the study's own sample-size justification or a statistical analysis plan. No calculated planning values are stated in the registry record for this explanation, so none can be interpreted.
For a fuller statistical assessment, the registry would need to report the primary estimate and uncertainty, the analysis population and model details, the handling of missing data, and the prespecified approach to secondary outcomes. Without those elements, the design and measurement can be described, but the primary efficacy finding and its robustness cannot be reconstructed.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 7 outcome measures: the primary HAM-D endpoint and six secondary measures. Those secondary outcomes cover anxiety, depression, global improvement, illness severity, and quality of life. Considering multiple outcomes can be useful for describing different aspects of a study, but it also creates a multiplicity question. In general, repeated testing across outcomes can increase the chance that at least one result appears statistically notable by chance. The registry does not report whether an adjustment, hierarchy, or other multiplicity strategy was prespecified or used.
The record reports one analysis, but does not provide a detailed analysis plan or explain how that entry relates to the outcomes listed. Results for the primary and secondary measures, including estimates and uncertainty, are not reported in the registry record. Accordingly, the consistency of findings across outcomes and the influence of multiplicity cannot be assessed.
For missing data, the primary outcome description says that Week 8 observations or last observation carried forward were used for the 6 participants who dropped out before completion. This identifies a missing-data procedure, but not its assumptions or sensitivity. The timing and reasons for dropout, the amount of data available before dropout, and alternative analyses are not reported in the registry record. As a general statistical concern, a carried-forward value treats the last observed score as a substitute for an unobserved later score; that substitution may not match the participant's actual unobserved outcome.
The registry labels the analysis population per protocol and states that it comprised 30 randomized subjects. It does not give criteria defining the per-protocol population or explain how that description relates to enrollment and dropout. An intention-to-treat analysis is not reported in the registry record. These omissions limit assessment of which participants contributed to the endpoint and whether analysis choices could influence the result.
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 |
|---|---|---|---|
| Ziprasidone | 1 | 30 | 3.3% |
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 |
|---|---|
| Ziprasidone | 20 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Ziprasidone |
|---|---|---|
| White Blood Cell Count Decreased | Immune system disorders | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ziprasidone |
|---|---|---|
| Headache | General disorders | 7 of 30 |
| Drowsiness | General disorders | 7 of 30 |
| Insomnia | General disorders | 6 of 30 |
| Fatigue | General disorders | 3 of 30 |
| Gastrointestinal Upset | Gastrointestinal disorders | 3 of 30 |
| Dry Mouth | General disorders | 3 of 30 |
Serious events with the highest arm-level rate: white blood cell count decreased (3.3%).
The registry records one participant with a serious adverse event among 30 at risk and 20 participants with other adverse events among 30 at risk. It lists White Blood Cell Count Decreased as a top serious term at 3.3%. Deaths are not reported in the registry record. These are registry entries and should be interpreted as reported counts and a reported term, not as a complete account of every event or its clinical course.
The serious-event count and other-event count describe different categories and should not be combined. The registry does not provide event descriptions, timing, duration, outcome, relationship assessment, or participant-level overlap between categories. The record also has no control group, so these figures cannot support a like-for-like comparison of event frequency with another treatment or with no treatment. The listed percentage does not, on its own, explain the number or circumstances of the events underlying the term.
Adverse-event counts are descriptive safety information. They do not establish that the intervention caused an event, and the absence of a reported event is not evidence that no such event occurred. Interpretation is limited to what the registry records.
12. What the Result Does, and Does Not, Mean
The study asks whether HAM-D scores changed from baseline to Week 8 among participants receiving open-label ziprasidone. The registry defines that endpoint and identifies the analysis approach as per protocol, with last observation carried forward used for participants who dropped out before completion. It also records limited adverse-event counts. These details explain what the study set out to measure and how some missing observations were handled.
The actual primary outcome values are not reported in the registry record. There is no reported mean change, baseline or follow-up mean, standard deviation, confidence interval, or test result. Consequently, the registry information does not establish whether HAM-D scores increased or decreased, how large any average change was, or how precisely it was estimated. The study's completed status does not answer those questions.
Even if a numerical before-and-after change were available, the single-group, open-label design would limit causal interpretation. A comparison with baseline can show that measurements differ over time, but there is no concurrent control group to indicate what would have happened over the same period without the study intervention. General factors such as symptom fluctuation and expectations could contribute to observed changes; whether they did so in this study is not reported.
The safety entries likewise do not provide a comparative estimate. The record reports one serious adverse event and 20 with other adverse events among 30 at risk, along with a serious-event term at 3.3%. Without detailed event information or a control group, those data cannot determine comparative risk or establish causation.
The appropriate interpretation is therefore bounded: the record describes a clinical question, design, endpoint, missing-data procedure, and selected safety figures, but it does not report the primary efficacy result needed to quantify change. It cannot support a conclusion about the direction, size, precision, or causal attribution of an efficacy effect.
13. Why This Trial Matters Statistically
This study is statistically instructive because it makes the distinction between measuring change and estimating a treatment effect especially clear. Its primary endpoint compares baseline with Week 8 HAM-D scores in a single group. That comparison can describe change over time, but it is not an estimate from a randomized, controlled contrast. Study design determines which questions an outcome analysis can answer, regardless of how familiar or clinically relevant the scale may be.
The record also illustrates why an endpoint definition is not a result. It specifies the 17-item scale, its score range of 0-54, and the direction of interpretation, but does not report the endpoint values. Without the mean change and a measure of uncertainty, readers cannot judge magnitude or precision. A completed study listing and a clearly named outcome do not replace the numerical estimate.
Missing-data handling is another important statistical feature. Last observation carried forward was used for the 6 participants who dropped out before completion. This makes explicit that later measurements were not available for those participants, but the record does not report the reasons for dropout or sensitivity analyses. General assumptions behind a missing-data method can affect the interpretation of an average change, so reporting the method alone is not enough to evaluate robustness.
Finally, the study lists multiple secondary outcomes without reporting their results or a multiplicity plan. This highlights the value of prespecified analyses and transparent reporting: readers need to know which comparisons were planned and how they were interpreted. The record offers design and measurement details that support a methodological discussion, while leaving the central efficacy estimate unreported.
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 important limitation for interpreting the registry entry is that the primary endpoint result is not reported in the registry record. The outcome definition is detailed, but the baseline and Week 8 scores, mean change, variability, confidence interval, and significance test are absent. The secondary outcome results are also not reported. This prevents an assessment of the direction, size, precision, or consistency of the findings.
The single-group design has no concurrent control arm, and masking is listed as none. A within-participant change therefore cannot isolate the effect attributable to ziprasidone from other influences over time. The record does not report details that would clarify how assessments were conducted or whether any additional safeguards addressed open-label measurement concerns.
The missing-data description is limited to use of Week 8 observations or last observation carried forward for the 6 participants who dropped out before completion. Reasons and timing of dropout, the handling of other missing measurements, and sensitivity analyses are not reported in the registry record. The meaning of the per-protocol population is also unclear: the record describes 30 randomized subjects but does not state the criteria used to define that population.
The registry does not report a detailed statistical analysis plan, the study's sample-size justification, or whether multiplicity was addressed across the 7 listed outcomes. It also does not give detailed adverse-event narratives, timing, or a comparison group. These limitations concern what can be established from the registry record and should not be treated as evidence that the unreported information was absent from study conduct or other records.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-Label Study of Geodon in Non-Rapid Cycling Bipolar II Patients With Major Depression — NCT00237666.
- Registry record last updated 2013-06-19; status last verified 2013-05.
- Results first posted 2013-06-19.
- 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
NCT00237666 is a completed Phase 4, open-label, single-group study of ziprasidone monotherapy in non-rapid-cycling Bipolar II patients with a major depressive episode. The intervention is described as 20-60 mg BID. Enrollment is listed as 30, and the primary endpoint is the baseline-to-Week 8 comparison of the 17-item HAM-D total score.
The registry describes a per-protocol analysis of 30 randomized subjects and says last observation carried forward was used for the 6 participants who dropped out before completion. It lists six secondary outcomes, but their results and the primary efficacy values are not reported in the registry record. Safety entries include one participant with a serious adverse event and 20 with other adverse events among 30 at risk; White Blood Cell Count Decreased is listed at 3.3%. The record does not report a control-group comparison, detailed statistical plan, or multiplicity approach.