Deep Brain Stimulation for Major Depressive Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Deep Brain Stimulation for Major Depressive Disorder (NCT00617162), a randomized na study. The primary outcome is Montgomery and Asberg Depression Rating Scale (MADRS) Score at Baseline and the Average of Months 4, 5, and 6.

2. Clinical Question

The study was designed to evaluate safety and efficacy in patients with major depressive disorder described as having substantial prior treatment exposure. Its primary measure was the Montgomery and Asberg Depression Rating Scale, or MADRS, assessed at baseline and using the average score from months 4, 5, and 6. Higher MADRS scores indicate more severe depression, while lower scores indicate less symptom severity.

The comparison is between two groups that both underwent implantation. The control group was not an unimplanted or no-procedure group: it received the implanted system but did not receive active stimulation during the first 6 months. The registry describes random assignment in a 2:1 ratio after implantation. The clinical question therefore concerns the difference in the measured outcome between these assigned strategies during the primary assessment period, not a comparison between surgery and no surgery.

The record lists secondary measures covering symptoms, functioning, quality of life, and adverse events. Those measures broaden the study's intended assessment, but do not substitute for a reported primary comparison. A single estimate of the primary effect, with its precision, is not reported in the registry record.

3. Trial Design

The record describes a prospective, multicenter, double-blind, randomized, controlled study of the Libra Deep Brain Stimulation System. The registered design is parallel-group and quadruple-masked. The phase is listed as NA. The study status is terminated, and the recorded enrollment is 125. The brief summary describes a plan to randomize 201 patients from up to 20 sites; the registry record does not explain the difference between that planned enrollment and the enrollment listed for the study.

According to the brief summary, potential participants were screened against eligibility criteria and underwent baseline evaluations before surgery. The summary describes three baseline evaluations, with the first two conducted by separate psychiatrists to confirm diagnosis. Following device implantation, participants were randomly assigned to active stimulation or control in a 2:1 ratio. The control group had the device implanted but did not receive active stimulation for the first 6 months. The primary outcome assessment was planned for 6 months, with follow-up continuing for 1 year.

The listed primary outcome is MADRS score at baseline and the average of months 4, 5, and 6. Secondary outcomes include MADRS at 1 year, several other symptom and functioning measures, quality of life, and adverse events over the study duration. The record lists 9 outcome measures. The record also lists one analysis, but its details and the analysis population are not reported in the registry record.

The study's stated prospective and masked design describes the intended structure, not proof that every planned procedure was completed as described. The registry record does not report details of the sequence generation, allocation concealment, masking procedures, or reasons for termination. Nor does it explain whether the planned follow-up and assessments were completed for all enrolled participants.

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 protocol allowed enrollment during the screening period. 125 were enrolled but only 90 continued on to receive DBS implants.

Overall Study

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 Montgomery and Asberg Depression Rating Scale (MADRS) Score at Baseline and the Average of Months 4, 5, and 6, measured over Baseline to 6 months.

The primary endpoint is the Montgomery and Asberg Depression Rating Scale (MADRS) score at baseline and the average of months 4, 5, and 6, with a stated timeframe of baseline to 6 months. MADRS is a ten-item questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score from 0 to 6, and the overall score ranges from 0 to 60. A higher score indicates more severe depression; a lower score indicates less symptom severity.

Using a repeated assessment period can represent symptom ratings across several months rather than relying on a single visit. In general, averaging repeated measurements can reduce the influence of a particularly unusual measurement, though it does not by itself resolve missing observations or other sources of bias. The registry record does not report how the average was calculated when a participant lacked one or more of the scheduled measurements.

The endpoint is clinically interpretable as a symptom-severity score, but interpretation of a treatment comparison requires the actual group results and a measure of uncertainty. A numerical primary comparison, confidence interval, and p-value are not reported in the registry record. The outcome description alone therefore establishes what was intended to be measured, not the size or precision of any between-group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design is randomized and parallel-group. Random assignment is intended, in general, to make treatment groups comparable on average at the point of assignment, including on characteristics that are not measured. It does not guarantee that groups are identical, and it cannot correct every source of bias after assignment. The record gives a 2:1 assignment ratio and says assignment occurred after implantation. Details of the randomization sequence and concealment are not reported in the registry record.

What does the primary score represent?

MADRS is a continuous outcome: a score can take values across a numerical scale, rather than placing every participant into only one category. The endpoint names the score at baseline and the average of months 4, 5, and 6. In general, an analysis of a continuous measure may compare group means, changes from baseline, or adjusted means. These approaches answer related but not identical questions. The registry record does not report which specific primary analysis was used, nor does it report numerical group means or a between-group estimate.

A mean describes the center of a set of scores. A standard deviation describes how dispersed individual scores are around their mean. The primary outcome description identifies the measure as a mean with standard deviation, but group-level primary values are not reported in the registry record. A standard deviation is not the same as the uncertainty in a group mean or in a treatment comparison; that uncertainty depends on the analysis and the amount of information available.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the analysis. Its width communicates precision: a wider interval indicates less precision than a narrower interval. A p-value, in general, describes how compatible the observed data are with a specified null model; it is not the probability that a treatment works or that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record, so the strength and precision of the primary evidence cannot be assessed from the registered outcome description.

These concepts also clarify why a point estimate alone would not be enough. A small estimated difference could be precise or uncertain, depending on the data and analysis; a larger estimate could also be uncertain. Interpretation should consider both magnitude and precision, alongside the outcome's clinical meaning. No primary estimate is reported to support that assessment.

What do the planning assumptions mean?

The sample-size illustration is described as planning based on the observed effect, not as the trial's original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% power or another stated power level; time-to-event illustrations use total events.

These are planning assumptions, not observed trial findings. An illustrative sample size does not show that the trial had a particular probability of finding a result, and it is not observed power. The registry record does not report the original sample-size justification or explain whether the study's actual design used these planning assumptions. The available record also does not provide numerical planning outputs for interpretation in this narrative.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. For outcomes such as counts, ignoring over-dispersion can make uncertainty look too small and can lead to overly confident conclusions. This is a general statistical concern, not a documented feature of this trial's MADRS results. The primary outcome is a continuous score, and the registry record does not report a model or evidence that over-dispersion was assessed.

For any analysis, the statistical model should match the outcome and design, and its assumptions should be assessed where possible. The record does not report the model, covariate adjustment, diagnostic checks, or sensitivity analyses for the primary endpoint. It is therefore not possible to evaluate those choices from the registry entry.

What can the safety counts establish?

For adverse events, the record gives numbers of participants at risk and numbers affected in each group. These counts are useful descriptive information. In general, a comparison of event proportions should also consider how events were defined, the duration participants were observed, whether participants could experience multiple events, and how incomplete follow-up was handled. Counts of participants affected are not interchangeable with counts of all event occurrences. The registry record does not give those additional details, so the listed safety figures should be read as reported participant counts rather than as a complete time-adjusted analysis.

No interim analysis plan, stopping rule, or full statistical analysis plan is reported in the registry record. The study's termination status does not establish whether interim monitoring occurred. The statistical details needed to reproduce or fully assess the primary analysis are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome that includes baseline and several follow-up time points, and it notes that the primary outcome has several categories or time points and was not reduced to one comparison. The intended primary assessment is described as the average of months 4, 5, and 6, but a single primary estimate is not reported. This leaves unclear how the registry's multiple time points were handled in the final analysis and which comparison, if any, was designated as the principal inferential test.

Multiplicity arises when several outcomes, time points, or subgroup comparisons are tested. In general, conducting many tests can increase the chance of a seemingly notable finding arising by chance; prespecified testing strategies can address this concern. The registry record does not report a multiplicity adjustment, a testing hierarchy, or how inference across the listed outcomes was controlled. It would be inappropriate to assume either that adjustment was or was not used.

The record lists secondary measures spanning symptoms, functioning, quality of life, and adverse events. Their presence does not establish that all were analyzed or that all results were reported. The analysis population, participant flow, missing-data frequency, reasons for missingness, and missing-data methods are not reported in the registry record. These omissions matter because incomplete outcome data can affect the estimated group comparison, particularly if missingness differs by group or is related to the outcome.

In general, an intention-to-treat analysis retains participants in the groups to which they were randomized, while other analysis populations may apply different inclusion rules. The registry record does not state which population was used for the primary analysis. It also does not report sensitivity analyses to evaluate the effect of missing data or alternative analysis choices. As a result, the robustness of the primary findings cannot be assessed from this record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: increase in depressive symptoms (16.7%), infection (8.3%), suicide or suicide attempt (6.7%), bariatric weight loss surgery (3.3%), suicidal ideation (3.3%).

The registry record lists serious adverse events for the DBS Active Treatment Group as 23 affected participants among 60 at risk, and for the DBS Control Group as 7 among 30 at risk. It lists other adverse events as 40 affected participants among 60 at risk in the active-treatment group and 24 among 30 at risk in the control group. Deaths are listed as 0 for each group.

The record's listed serious-event terms include increase in depressive symptoms at 16.7%, infection at 8.3%, suicide or suicide attempt at 6.7%, bariatric weight loss surgery at 3.3%, suicidal ideation at 3.3%, and seizure or convulsion at 3.3%. The record does not identify group-specific denominators for these term percentages, so they should not be used to compare groups.

In general, adverse-event summaries require attention to the distinction between participants affected and event occurrences. A participant can potentially experience more than one event, and the record does not provide event-level counts or timing. Nor does it report exposure-adjusted rates, detailed event definitions, or the duration of observation for each participant. The figures are therefore descriptive registry counts and should not be read as a complete assessment of comparative safety.

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

The registry record establishes that a randomized, parallel-group study was registered to compare active deep brain stimulation with an implanted control strategy that withheld active stimulation for the first 6 months. It identifies MADRS as the primary measure and gives its intended assessment period and scoring direction. It also records selected adverse-event counts and lists several serious-event terms.

Those details do not establish the magnitude, direction, or precision of the primary treatment comparison. The primary outcome description is not a result, and the registry record does not report a single numerical estimate, confidence interval, or p-value for the primary question. It is therefore not possible from this record to state how much the groups differed on MADRS or how uncertain such a difference was.

The safety entries likewise do not establish a complete comparative safety profile. They are counts of affected participants within the listed group denominators, with no reported exposure-adjusted analysis or detailed account of event timing and classification. The listed terms and percentages are descriptive entries, not evidence on their own of causation or of a difference between groups.

In general, a randomized design can support a causal comparison when the trial is conducted and analyzed as planned, but interpretation also depends on implementation, follow-up, outcome completeness, and analysis choices. The registry record does not report enough detail to evaluate those elements fully. Its terminated status should not be treated as a result or as an explanation for the absence of a primary estimate.

The appropriate reading is consequently limited: the registered question, study structure, endpoint, and some safety counts can be described, but the posted information does not permit a complete judgment about the primary outcome. It also does not support conclusions about results beyond those explicitly recorded.

13. Why This Trial Matters Statistically

This trial illustrates why a registry entry's endpoint description and design are not substitutes for an interpretable result. The record specifies a randomized comparison and a continuous symptom-severity measure, but it does not provide a single primary comparison estimate or its uncertainty. Without those quantities, readers cannot assess the observed magnitude or precision of the primary result.

The primary endpoint also involves repeated assessments: baseline and an average across months 4, 5, and 6. Such a definition makes the analysis question depend on how repeated measurements were combined and how missing visits were handled. The registry record does not report those details. This is an important statistical distinction: a well-defined measurement schedule does not by itself define the complete analysis.

The trial also shows why safety counts need context. Counts of participants affected can communicate the recorded burden, but interpretation depends on denominators, follow-up duration, event definitions, and whether the measure counts people or events. The record gives some participant denominators and counts, but not enough detail for a time-adjusted or fully specified comparison.

Finally, the record distinguishes design planning from results. Its sample-size illustration is explicitly based on the observed effect under stated assumptions, while the original sample-size justification is not reported. Such planning illustrations should not be mistaken for evidence that the study was adequately powered or that a treatment effect was demonstrated. The central statistical lesson is that design, outcome definition, analysis, and reporting must be considered separately to understand what a clinical trial can establish.

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 record reports the study as terminated but does not give the reason for termination. Although the brief summary describes a planned enrollment of 201, the recorded enrollment is 125; the registry record does not explain the difference or provide a detailed participant flow. The safety denominators are 60 and 30, and their relationship to the recorded enrollment is not explained.

The primary endpoint is described, but the record does not provide a single numerical primary comparison or its uncertainty. It also does not report the primary analysis model, analysis population, handling of missing measurements, or a detailed statistical analysis plan. The note that the primary outcome has several categories or time points and was not reduced to one comparison further limits interpretation of the intended primary result.

The record describes masking and randomization, but operational details are not reported. It does not give the allocation-concealment method, explain how masking was maintained, or report whether participants, clinicians, and assessors remained masked throughout follow-up. The planned sample-size justification, interim analyses, and stopping rules are not reported in the registry record.

For safety, the available entries do not describe event definitions, event timing, duration of exposure, or whether the percentages for serious-event terms are group-specific. The participant counts do not indicate how many total event occurrences took place. These limitations mean that the registered information is useful for describing the study's planned comparison and selected safety summaries, but is insufficient for a full appraisal of efficacy, safety, or the conduct of the final statistical analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Deep Brain Stimulation for Major Depressive Disorder — NCT00617162.
• Registry record last updated 2024-04-08; status last verified 2024-04.
• Results first posted 2024-04-08.
• 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.

18. Record Summary

NCT00617162 is a terminated, randomized, parallel-group study of the Libra Deep Brain Stimulation System for major depressive disorder. The registry lists quadruple masking, recorded enrollment of 125, and a planned 12-month follow-up. Its brief summary describes active stimulation compared with an implanted control system without active stimulation during the first 6 months, assigned in a 2:1 ratio.

The primary measure is MADRS score at baseline and the average of months 4, 5, and 6. Higher scores indicate more severe depression. The registry record does not report a single primary comparison estimate or its precision. It lists 9 outcome measures and selected adverse-event counts, including serious events, other events, and deaths. Reasons for termination, detailed analysis methods, missing-data handling, and the original sample-size justification are not reported in the registry record.