Dichotic Listening as a Predictor of Medication Response in Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dichotic Listening as a Predictor of Medication Response in Depression (NCT00404755), a non-randomized phase 4 study. The primary outcome is Hamilton Depression Scale (HAM-D).

2. Clinical Question

3. Trial Design

The registry describes a completed Phase 4 study with non-randomized allocation, no masking, and a single-group model. Enrollment is listed as 17. The study began in 2006-07 and its primary completion is listed as 2011-08. The brief summary says the study would recruit 100 depressed patients; that planned figure differs from the registry’s reported enrollment, and the record does not explain the difference. Enrollment should not be mistaken for the number contributing data to every medication-specific outcome.

Three drug interventions are listed. Escitalopram began at 10 mg/d for 1 week, with increases by 10 mg/week if tolerated and not remitted, to a maximal dose of 40 mg/d. Bupropion extended release (XL) began at 150 mg/d for a week, then 300 mg/d for a week and then 450 mg/d, with increases if tolerated and not remitted. Imipramine began at 50 mg/d, increasing twice weekly by 50 mg/increase to 200 mg/d, then by 50 mg/week to a maximum dose of 300 mg/d, with increases if tolerated and not remitted.

Because allocation was non-randomized, differences between medication-specific groups may reflect how participants entered or received treatment as well as any treatment-related differences. The record does not report the allocation procedure, reasons for medication selection, or whether participants could contribute to more than one medication group. The endpoint population is described as participants given that medication, so its definition is medication-specific. Clinical Global Impression Scale (CGI) is listed as a secondary outcome. The record lists two outcome measures and zero analyses; it does not report numerical results for either outcome.

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: Patients had to have not taken psychotropic medication for at least two weeks (no fluoxetine for at least 5 weeks) and had to produce a urine negative for commonly abused substances. Current use of psychotropic medication or a positive urine toxicology screen would abort further study participation.

Phase I (Bupropion)

Reasons for not completing this period:

Phase II (Escitalopram)

Reasons for not completing this period:

Phase III (Imipramine)

Analysis population for the primary outcome, as defined in the registry: Participants were included if they were given that medication

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 Hamilton Depression Scale (HAM-D), measured over 6 weeks or last visit in Phase.

The primary endpoint is the Hamilton Depression Scale (HAM-D), 21 item version. It summarizes all 21 items, with scores ranging from 0 to a maximum of 63; a higher score means worse depression. The registry gives the outcome unit as units on a scale and identifies the statistic as a mean with standard deviation. The assessment time is 6 weeks or the last visit in Phase.

A continuous symptom scale can describe the level of measured symptoms across participants and can capture variation in scores, rather than reducing each person’s result to a yes-or-no category. A mean conveys the group’s average score, while a standard deviation describes how dispersed individual scores are around that mean. These are general interpretations of the stated summary statistics; the registry record does not give the observed mean or standard deviation.

The HAM-D is relevant to the stated focus on medication response because the registry identifies it as the primary measure of depression symptoms. However, a HAM-D result alone would not show whether perceptual laterality preferences predict response. That would require a reported analysis connecting the laterality measure to treatment response. The registry record does not report such an analysis, the specific laterality measure, or numerical HAM-D findings. CGI is listed as a secondary outcome, but its measurement details and results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. These statistics answer different descriptive questions. A mean locates the center of the measured scores, while a standard deviation describes how much scores vary around that center. Neither statistic alone shows the full distribution of participants’ scores, and neither establishes that a change is attributable to a medication. The HAM-D score direction is explicit: higher scores indicate worse depression.

What would a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method. A narrow interval indicates greater precision for that estimate than a wide interval, while an interval that spans values with materially different interpretations leaves more uncertainty. An interval is not a guarantee that the true value lies within its limits. The registry record does not report a confidence interval for the HAM-D outcome or for the association motivating the study, so no estimate of precision for those results can be assessed.

What does a significance test address?

In general, a significance test evaluates how compatible the observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, does not quantify the size or importance of an effect, and does not replace an estimate with an uncertainty interval. The registry record does not report p-values or a specific inferential analysis for the primary endpoint. It also does not report the test, model, covariates, or statistical decision rules used.

Why does the design matter for analysis?

Allocation is listed as non-randomized, masking as none, and the model as single group. In general, randomization is used to reduce systematic differences between groups in expectation, and masking can limit some forms of expectation or assessment bias. Without randomized allocation, a medication-specific comparison can be influenced by the characteristics of the people who received each medication. Without masking, knowledge of treatment may influence some assessments or behaviors. These are general design considerations, not evidence that a particular bias occurred in this study.

The outcome population is described as participants who were given that medication. This makes the interpretation dependent on knowing how medication exposure and outcome availability were determined. The record does not report whether participants could receive multiple listed medications, how changes in treatment were handled, whether the primary endpoint was measured for all enrolled participants, or how incomplete measurements were treated. The medication-specific safety denominators alone cannot answer those questions.

How should planning illustrations be read?

In general, sample-size planning asks how much information might be needed to detect an effect under stated assumptions. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The registry also specifies that time-to-event illustrations use total events under the Schoenfeld method, while other illustrations use participants per arm. Such figures are planning illustrations, not outcomes observed in the trial and not observed power.

Planning calculations depend on their assumptions and on the effect used as a target. They do not show that a study had a particular probability of detecting an effect after the results are known. The registry record does not give the observed effect or numerical planning estimates, so those assumptions cannot be translated into a study-specific interpretation of precision or adequacy. The planned recruitment figure in the brief summary is not, by itself, a statistical justification; the sample-size justification is not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model assumes. If a model understates variability, uncertainty intervals can be too narrow and significance tests can be too optimistic. This concern is relevant only when the chosen model’s assumptions and data structure make it applicable. The registry does not report a model for the HAM-D outcome, any dispersion assessment, or a statistical plan, so it is not possible to determine whether over-dispersion was assessed or relevant to the analyses.

The registry lists two outcome measures and zero analyses. These entries do not supply results, modeling details, or an account of how the motivating prediction question was tested. The analysis method, treatment of repeated or last-visit measurements, covariate adjustments, and any interim analyses are not reported in the registry record. Without those details and outcome estimates, statistical interpretation must remain limited to the design and outcome definitions that are recorded.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Bupropion", "Escitalopram", "Imipramine")
n   <- c(17, 10, 3)
m   <- c(11.2, 9.7, 11.3)
sp  <- c(7.9, 6.4, 8.1)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Bupropion  17  11.200  7.900  7.138  15.262
CARM  Escitalopram  10  9.700  6.400  5.122  14.278
CARM  Imipramine  3  11.300  8.100  -8.822  31.422

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: HAM-D as the primary outcome and CGI as a secondary outcome. It does not report how many statistical hypotheses were tested, whether multiple comparisons were planned, or whether any adjustment for multiplicity was used. In general, testing several outcomes or comparisons can increase the chance of at least one apparently notable result by chance; adjustment methods can address that issue but may also affect precision. No conclusion about multiplicity control can be drawn from the record.

Missing-data handling is not reported in the registry record. The primary assessment is defined as 6 weeks or the last visit in Phase, but the record does not explain how a last visit was selected, what happened when a participant lacked a measurement, or whether any imputation or other missing-data method was used. It does not report the number with an observed HAM-D value at the assessment time. Therefore, the completeness of endpoint data and the possible influence of missing outcomes cannot be evaluated from the registry record.

The primary outcome population is described as participants who were given the relevant medication. The record does not further define the analysis population, state whether participants were analyzed according to initial or received treatment, or explain handling of treatment changes. It also does not provide a flow of participants through the medication groups. Zero analyses are listed in the registry, so no analysis population or analysis-specific denominator can be confirmed. These omissions limit the ability to connect the enrollment figure to the set of participants underlying any treatment-response estimate.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: allergic reaction (5.9%).

The registry reports serious adverse events for the medication groups as follows: Escitalopram, 0 of 11 at risk; Bupropion, 1 of 17; and Imipramine, 0 of 3. For other adverse events, it reports 10 of 11 for Escitalopram, 10 of 17 for Bupropion, and 3 of 3 for Imipramine. These are counts within the recorded denominators, not randomized comparisons. The denominators differ, and the record does not state whether participants appear in more than one medication group.

The serious adverse event terms list allergic reaction at 5.9%. The record does not provide further detail connecting that term to a specific participant or medication group beyond the serious-event information recorded. Death counts are not reported in the registry record.

Serious and other adverse events are distinct categories in the registry. A count of other adverse events should not be read as a count of serious events. Counts also do not establish cause: an event recorded during treatment is not necessarily caused by that treatment. In general, safety comparisons require attention to group definitions, time at risk, event ascertainment, and participant overlap. Those details and a comparative safety analysis are not reported in the registry record, so the listed figures are descriptive only.

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

The record documents a study motivated by the possibility that perceptual laterality preferences might be related to response to depression treatment, with particular interest in whether a previously observed association would also be found with bupropion. It identifies HAM-D as the primary endpoint and CGI as a secondary outcome, and gives medication dosing schedules and a study design. These details describe what the study set out to examine, not what it found.

No numerical HAM-D results, CGI results, effect estimates, confidence intervals, or p-values are reported in the registry record. The record lists zero analyses. It therefore does not support a statement about the direction, size, or precision of treatment response, or about whether laterality preferences predicted response. The planned recruitment figure of 100 and the recorded enrollment of 17 do not substitute for outcome data.

The design also limits what can be inferred from any medication-specific differences that might be reported elsewhere. Non-randomized allocation means the groups are not established as comparable by random assignment, and the record describes no masking. In general, differences in participant characteristics, medication selection, or measurement can complicate causal interpretation. The registry does not report enough information to determine how these issues were addressed.

These limitations do not mean that the study question is unimportant, nor do they show that a treatment has or has not worked. They mean that the registry record, as described, can establish the study’s recorded structure and endpoints but cannot establish an outcome conclusion. A reader should distinguish the rationale for asking a prediction question from evidence answering it, and descriptive safety counts from comparative safety estimates.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a predictive question and a treatment comparison. The stated motivation concerns whether perceptual laterality preferences are associated with treatment response. Answering that question requires reporting how the preference was measured and an analysis relating it to response. A HAM-D endpoint can measure depression symptom scores, but the scale outcome alone does not demonstrate that a baseline characteristic predicts response. The registry record does not report the prediction analysis or numerical results.

The design also matters to the interpretation of medication groups. Non-randomized assignment and a single-group model do not establish balanced treatment groups through randomization. Thus, comparisons among people receiving escitalopram, bupropion, or imipramine would need careful qualification, particularly if participants differed in ways related to medication selection or outcome. The registry does not describe the selection process sufficiently to assess that possibility.

Finally, the entry illustrates why outcome definitions, analysis populations, and results must be considered together. It specifies a mean HAM-D score, standard deviation, and an assessment time, but does not report the estimates or who contributed to an analysis. Without those details, neither effect magnitude nor precision can be judged. For clinical researchers and biostatisticians, the record is useful for identifying a research question and design features while also showing the limits of interpretation when analysis details and numerical outcomes are absent.

15. 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 registry record does not report numerical results for the primary or secondary outcomes, despite listing HAM-D and CGI as outcome measures. It lists zero analyses and gives no effect estimates, uncertainty intervals, or inferential results. The laterality measure described in the study’s motivation is not specified as an outcome measure in the record, and no analysis linking it to treatment response is reported.

Important design and analysis details are also absent. Although the study is listed as non-randomized, unmasked, and single group, the allocation process and medication-selection criteria are not reported. The record does not clarify whether participants received more than one listed medication. It also does not report baseline characteristics by medication, outcome completeness, missing-data methods, covariate adjustments, or the analysis population beyond the statement that participants were included if given the medication.

The brief summary describes recruitment of 100 depressed patients, while enrollment is recorded as 17; the registry does not explain the difference. This makes it especially important not to assume that enrollment is equivalent to the number analyzed for each endpoint. The different medication-specific safety denominators are recorded, but their relationship to enrollment and to one another is not explained. Serious adverse event counts, other adverse event counts, and the listed allergic reaction term are descriptive and do not provide a randomized comparison.

The statistical plan, sample-size justification, interim analyses, and methods for handling multiple outcomes are not reported in the registry record. Consequently, the adequacy of the planned design, precision of any effect, and robustness of the analysis cannot be assessed from this information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dichotic Listening as a Predictor of Medication Response in Depression — NCT00404755.
• Registry record last updated 2018-04-30; status last verified 2018-03.
• Results first posted 2018-03-15.
• 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.

19. Record Summary

The registry identifies a completed Phase 4, non-randomized, unmasked, single-group study with enrollment of 17. The stated research motivation concerns whether a previously reported association between treatment response and perceptual laterality preferences would also be found with bupropion. Escitalopram, bupropion, and imipramine are listed as interventions.

The primary endpoint is mean HAM-D score, with standard deviation, at 6 weeks or the last visit in Phase. CGI is listed as a secondary outcome. The registry also records medication-specific adverse-event counts. It does not report numerical outcome results, a prediction analysis, or statistical methods beyond the stated planning-illustration assumptions. Therefore, the record describes the study question and design but does not establish the observed treatment response or the proposed association.