A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression (NCT00422162), a randomized phase 4 study. The primary outcome is Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, phase 4 study with quadruple masking. Its official title describes an eight-week study comparing duloxetine 60 mg and 120 mg per day in patients hospitalized for severe depression. The registry record reports enrollment of 339 participants and a completed status. The start is recorded as 2007-02 and primary completion as 2008-08.

The two arm descriptions specify dose regimens that could change after Week 4 according to responder status. The 60 mg arm began with morning duloxetine and an evening placebo. Responders continued that regimen, while nonresponders received an additional evening duloxetine dose. The 120 mg arm began with duloxetine morning and evening; responders continued, while nonresponders continued that regimen with an evening placebo capsule added. The record does not report the response criterion or explain how response status was determined.

Randomization can help balance measured and unmeasured participant characteristics across assigned groups, while masking is intended to limit the influence of treatment knowledge on care, reporting, and assessment. The registry record labels masking as quadruple but does not identify the masked roles. It also does not report the allocation ratio, group sizes, or further details of randomization. The two arms and their changing regimens should therefore be understood from the descriptions recorded, without assuming additional treatment or allocation details.

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: Of the 392 patients who signed informed consent, 339 were randomized.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, measured over Baseline to Week 4.

The primary endpoint was change from baseline to the Week 4 endpoint in total score on the Montgomery–Åsberg Depression Rating Scale (MADRS). The scale is described as a 10-item checklist, with each item rated from 0 to 6 and a total score ranging from 0 to 60. The record describes lower scores as indicating lower severity of depressive symptoms and higher scores as indicating higher severity.

A change score expresses how a participant’s measured value differs from their baseline value. Summarizing such scores with a mean describes the average change in the analyzed group; the standard deviation describes the spread of individual change scores around that mean. These quantities answer different questions: the mean characterizes the group average, while the standard deviation conveys how variable the participant-level changes were.

In general, a symptom scale can provide a structured way to track severity over time and compare group-level patterns. Interpretation depends on the scale’s content, the population measured, and the completeness and timing of observations. The registry record does not report the arm-level mean changes, standard deviations, or a single primary comparison, so the magnitude and precision of the observed endpoint cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a randomized, parallel-group comparison and a continuous primary measure summarized by a mean and standard deviation. It does not report the statistical test or model used for the primary comparison, nor does it give a numerical estimate of that comparison. The following explains the general statistical concepts relevant to those recorded design and outcome features, without attributing an unreported method to the study.

What does randomization contribute?

In general, random allocation is intended to make treatment groups comparable at the start of a study, including with respect to characteristics that may affect an outcome. It does not guarantee identical groups, especially when groups are smaller, and it does not by itself prevent missing outcomes or measurement bias. A comparison remains dependent on how participants are analyzed, how outcomes are measured, and whether the analysis matches the study question. The allocation ratio, group sizes, and details of the randomization procedure are not reported in the registry record.

What does a mean change describe?

For a continuous outcome such as a total symptom score, a mean change is the average of participant-level changes over the specified period. The endpoint’s timeframe is baseline to Week 4. A group mean describes the center of the observed or analyzed changes; it does not imply that every participant changed by that amount. The standard deviation describes dispersion among individual values, rather than uncertainty in the estimated group mean. A confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the statistical method used. It is not a range containing every individual’s outcome.

For a treatment comparison, the central statistical quantity is commonly a contrast between groups, with an uncertainty measure. That contrast would help distinguish the estimated difference from the variation expected from sampling. The registry record does not provide the primary contrast or its confidence interval, and it does not report a p-value for a single primary comparison. No direction or statistical significance can therefore be inferred from the endpoint description alone.

Why can outcome dispersion matter?

In general, the standard deviation helps describe how spread out continuous observations are. If a measure has greater variability than a model assumes, uncertainty estimates based on that model may be inaccurate. Over-dispersion is a concern particularly for outcomes whose variability exceeds the model’s assumptions. The registry record reports standard deviation as the dispersion measure for the primary endpoint, but does not provide its values or describe a model or diagnostic assessment. It is therefore not possible to assess the observed dispersion or whether any special variance method was used.

What does last observation carried forward mean?

The primary analysis population is described as randomized participants who received at least one dose and had a baseline and at least one post-baseline value, with last observation carried forward. In general, this imputation approach uses a participant’s last recorded outcome to fill a later missing outcome. It produces a complete value for the specified analysis, but it relies on assumptions about how the unobserved outcome relates to the last observed value. If participants’ scores would have continued to change after their last measurement, carrying that value forward may not represent their later outcome. The registry record does not report how many observations were imputed or provide sensitivity analyses using other missing-data approaches.

What can a planning illustration tell readers?

The record describes sample-size planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not results about the trial’s achieved power. The record does not provide the trial’s own sample-size justification or make those illustrations evidence that a particular effect was established. A planning calculation asks what sample size might be needed under its assumptions; it does not replace the estimated treatment contrast and its uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures and 5 analyses. It identifies the MADRS change endpoint as primary and lists secondary outcomes that include other depression scales, clinician and patient global-impression measures, anxiety scores, rescue-option evaluations, and responder percentage. Having multiple outcomes or analyses raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase if each is assessed without adjustment. The registry record does not report whether a multiplicity adjustment or a prespecified hierarchy was used.

The primary outcome is not represented in the record as one numerical comparison; it is described as having several categories or time points. The record also does not report a statistical analysis plan, the testing strategy across outcomes, or which analyses were confirmatory versus exploratory. It is therefore not possible to determine how the reported analyses were prioritized or how any multiplicity was handled.

For missing data, the record specifies an analysis population requiring treatment exposure and baseline plus at least one post-baseline value, and identifies last observation carried forward. It does not report the number excluded from this population, missingness by group, reasons for missing measurements, or results under alternative assumptions. In general, missing-data methods can affect estimates if the probability of missingness is related to observed or unobserved outcomes. The available description is not enough to assess that possibility or the sensitivity of findings to the imputation approach.

11. What the Result Does, and Does Not, Mean

The record establishes that a randomized, eight-week study compared two duloxetine dose regimens among patients hospitalized for severe depression, and that the primary endpoint concerned change in MADRS score through Week 4. It does not report a single numerical primary comparison. Consequently, the registry record alone does not show the direction or size of a between-group difference, or how precisely that difference was estimated.

A trial’s design and endpoint description should not be confused with evidence about the endpoint result. Enrollment of 339 participants and completed status do not indicate the result of the primary analysis. Nor does the presence of secondary outcomes establish that any one outcome favored either regimen. Interpreting such results would require their estimates, uncertainty, analysis populations, and relevant multiplicity approach.

The safety entries are counts of affected participants, with no at-risk denominators reported for either group. Counts alone do not provide the likelihood of an event in each group, and the listed serious-event percentages lack a specified denominator in the registry record. They should not be treated as directly comparable rates.

In general, statistical uncertainty concerns how much an estimate may vary across comparable samples under the analysis assumptions. A confidence interval can communicate that uncertainty, while a p-value addresses compatibility with a specified null model; neither alone conveys clinical importance. No primary effect estimate, confidence interval, or p-value is reported, so those distinctions cannot be applied to a numerical primary result. The registry record supports a description of the study’s design and planned outcome, but not a conclusion about the comparative endpoint result.

12. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint description is not the same as a report of an analyzable treatment contrast. The registry record identifies a continuous symptom-scale outcome, a defined follow-up period, and a mean with standard deviation as the outcome summary. Those details help readers understand what was intended to be measured. Without group-level estimates and their uncertainty, however, the central statistical comparison cannot be interpreted.

The dosing descriptions also show how a randomized study can include treatment changes linked to participant response during follow-up. Such a design requires careful interpretation of what comparison is being made and at what time. The record describes the dose changes but does not give the response criterion or report a detailed statistical plan. Those omissions limit the ability to connect the treatment sequence to a specific estimand, meaning the precise treatment effect the analysis seeks to estimate.

The missing-data description is another important statistical feature. Last observation carried forward is explicit, but the record does not report the number of imputed values or analyses testing alternative assumptions. This makes the sensitivity of the primary result to missing measurements impossible to assess from the registry record.

Finally, the study lists multiple outcomes and analyses but does not report the approach to multiplicity. In general, that information helps readers distinguish a primary confirmatory comparison from secondary or exploratory findings. Taken together, the record offers useful design and measurement details while demonstrating why outcome estimates, uncertainty, analysis populations, and analysis-plan information are essential for statistical interpretation.

13. 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 principal limitation for interpreting this trial from the registry record is the absence of a single numerical result for the primary endpoint. Arm-level mean changes and standard deviations are not reported, nor is a between-group estimate with an uncertainty interval or p-value. The record therefore does not support a quantitative account of the primary comparison.

Important design and analysis details are also not reported in the registry record. These include the number assigned to each arm, the randomization procedure and allocation ratio, the roles covered by quadruple masking, the response criterion used at Week 4, and the statistical test or model for the primary endpoint. The record does not provide the trial’s sample-size justification or a detailed statistical analysis plan.

The stated analysis population excludes randomized participants who did not meet the listed treatment-exposure and measurement requirements, but the number included and reasons for exclusion are not reported. Although last observation carried forward is specified, the number of imputed values and sensitivity analyses are not reported. The multiplicity approach for the 16 outcome measures and 5 analyses is also not described.

For safety, group-specific counts at risk are not reported. The counts of participants affected by serious and other adverse events therefore cannot be interpreted as incidence proportions from this record. The denominator for the listed serious-event percentages is also not specified. These are limitations of the available registry information; they do not establish what was or was not available in other study materials.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression — NCT00422162.
• Registry record last updated 2011-07-26; status last verified 2011-07.
• Results first posted 2009-10-02.
• 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.

17. Record Summary

The registry record describes NCT00422162, a completed phase 4 randomized, quadruple-masked, parallel-group study of duloxetine dose regimens in patients hospitalized for severe depression. Enrollment was 339, and the study duration was eight weeks. The primary outcome was change from baseline to the Week 4 endpoint in total MADRS score, summarized as a mean with standard deviation. The primary analysis population required at least one dose, a baseline value, and at least one post-baseline value, with last observation carried forward.

The two arm descriptions include treatment continuation or dose changes after Week 4 according to responder status. The record lists 16 outcome measures and 5 analyses, but does not report a single numerical primary comparison, a detailed analysis plan, or group-specific adverse-event denominators. As a result, it describes the design and endpoint but does not allow the primary comparative estimate or its precision to be assessed.