rTMS in Treatment Resistant Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for rTMS in Treatment Resistant Depression (NCT02080507), a randomized na study. The primary outcome is Depression Severity as Assessed by the Montgomery Åsberg Depression Rating Scale (MADRS) Score.

2. Clinical Question

The study’s stated purpose was to investigate the safety and efficacy of rTMS as an alternative treatment to ECT. It also aimed to provide data for planning a larger clinical trial if there were evidence of a clinically relevant treatment effect. The randomized comparison described in the record, however, was active versus inactive rTMS. That distinction matters: the listed control condition was not ECT, so the randomized comparison does not directly estimate a difference between rTMS and ECT.

The clinical question that can be framed from the outcome listing is whether depression severity, measured by MADRS, differed between the active and inactive groups over the stated assessment timeframe. The registry names baseline and Week 6 but does not present the group values, change estimates, confidence intervals, or a test result. Consequently, the direction, size, and precision of any difference cannot be assessed from the posted results. The question is identifiable; its numerical answer is not reported in the registry record.

3. Trial Design

The record describes a randomized, parallel-group study with quadruple masking. Participants were assigned to an active or inactive Neuronetics rTMS stimulator. In the active group, magnetic power output was delivered through the coils; in the inactive group, no magnetic power output was delivered through the coils. The record lists enrollment of 12 and a completed status. The phase is listed as NA.

The study start is listed as 2014-03 and primary completion as 2015-12. These dates and the completed status describe the recorded conduct timeline, but do not establish when each participant was assessed or how many completed each assessment. Participant flow, withdrawals, and reasons for discontinuation are not reported in the registry record.

Random assignment is intended to make the groups comparable on average at the start of a trial, including on factors that may affect the outcome. With a small enrollment, randomization does not guarantee that every prognostic characteristic is balanced. The record does not provide baseline group characteristics, details of the randomization procedure, or information about allocation concealment, so those aspects cannot be evaluated from the registry description.

Quadruple masking indicates that the record classifies the study as masked at four levels, but it does not identify those levels or explain how masking was maintained. No further masking procedures are reported in the registry record. The parallel design means the groups were separate rather than a crossover in which participants received both conditions in sequence; no crossover is described.

The record lists two outcome measures, including the primary MADRS measure and a secondary quality-of-life measure. It reports zero analyses. The actual analysis plan, the definition of the analysis population, and numerical outcome findings are not reported in the registry record. The record’s description of sample-size illustrations is separate from the trial’s design and does not provide evidence about the trial’s achieved statistical power.

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: Participants taking psychotropic medications were required to be stable on a stable dose for at least six weeks.

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 Depression Severity as Assessed by the Montgomery Åsberg Depression Rating Scale (MADRS) Score, measured over Baseline, Week 6.

The primary endpoint is depression severity assessed by the Montgomery Åsberg Depression Rating Scale (MADRS), with measurements listed at baseline and Week 6. The registry description characterizes MADRS as a diagnostic questionnaire used by psychiatrists to measure the severity of depressive episodes in people with mood disorders. It states that a higher score indicates greater depressive symptoms.

The description also says that the MADRS is a ten-item questionnaire and that the MADRS-S instrument has nine questions, with an overall score ranging from 0 to 60 points. The record does not explain the relationship between these descriptions or specify which version was used to generate the endpoint result. That instrument detail should therefore be interpreted as written rather than resolved by assumption.

A repeated symptom measure can be used to describe severity at different assessments and to evaluate whether groups’ scores change or differ over time. Baseline assessment can describe starting severity, while a later assessment can provide information about status after treatment. To interpret a group comparison, readers would need the relevant group values and an estimate of the difference, ideally with a measure of uncertainty. Those numerical results are not reported in the registry record.

The registry lists a secondary outcome assessing quality of life using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-Les-SF) score. No numerical findings for that outcome are reported in the registry record either. Naming an instrument and its timeframe identifies what was intended to be measured; it does not by itself establish the size, direction, or precision of an observed treatment difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison. Randomization assigns participants to study arms by chance, with the aim of reducing systematic differences between groups at the start. It does not ensure identical groups, particularly in a study with limited enrollment. Baseline characteristics are useful for describing the enrolled groups and checking for apparent imbalances, but those characteristics are not reported in the registry record.

What a mean and standard deviation describe

The primary outcome is identified as a continuous measure summarized by a mean and standard deviation. In general, a mean describes the center of a group’s scores, while a standard deviation describes how spread out individual scores are around that mean. They answer different questions: the mean concerns average severity, and the standard deviation concerns participant-to-participant variation. Neither group’s mean or standard deviation is reported in the registry record, so no observed score distribution can be described.

When a continuous outcome is measured at baseline and a later assessment, an analysis might compare later scores, changes from baseline, or the pattern across timepoints. Those approaches can target different estimands and rely on different modeling choices. The registry names baseline and Week 6, but the actual analysis method, the precise contrast, and whether baseline adjustment was used are not reported in the registry record. No particular analysis should be attributed to the trial without that information.

Interpreting estimates and uncertainty

A between-group estimate describes the size and direction of a contrast according to the selected analysis. A confidence interval gives a range of values that are compatible with the observed data under the method’s assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. Statistical significance and clinical importance are distinct: a test result does not by itself establish whether a difference would be meaningful to patients or clinicians. The registry record provides no primary-outcome estimate, interval, or test result, so these concepts cannot be applied to a numerical finding for this trial.

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be, if that hypothesis and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, nor a measure of effect size. Since no p-value is reported, there is no basis to characterize the primary comparison as statistically significant or not statistically significant.

Planning calculations are not trial results

The record describes sample-size calculations as planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. These assumptions describe a calculation framework, not the trial’s observed clinical findings. A planning illustration asks how many participants per arm might be needed to detect a specified fraction of an observed effect under stated assumptions. It does not show that the trial had that power, nor does it substitute for an analysis of outcome data.

Power is a design-stage probability defined relative to a particular effect, variability, significance threshold, and analysis. “Observed power,” calculated after a study from its observed effect, does not add a useful independent measure of evidence beyond the estimate and its uncertainty. Sample-size illustrations should therefore be read as conditional planning scenarios. The numerical illustrations and effect fractions are not reported in the registry record, and the registry does not report a sample-size justification for the trial itself.

Over-dispersion and model choice

For general context, over-dispersion occurs when observed variation is greater than a statistical model expects. If a model underestimates variation, its standard errors may be too small and its confidence intervals too narrow. This issue is most directly relevant to particular outcome distributions and models; it should not be presumed for this continuous endpoint. The registry record does not report a model, diagnostic checks, or an assessment of over-dispersion.

For a continuous score, analysis choices can include modeling assumptions about the score distribution, the relationship between measurements over time, and the treatment contrast. A small sample can make those assumptions and the stability of estimates especially important. The record does not state whether a model was used, how assumptions were assessed, or how any departures were handled. These are methodological considerations in general, not descriptions of analyses known to have been performed in this trial.

Masking and outcome measurement

Masking can reduce the influence of expectations on participant reports, clinical assessments, or study conduct. The registry classifies this study as quadruple masked, but it does not identify the four groups of people covered by that designation or describe the masking procedures. The MADRS is described as a clinician-used questionnaire. The record does not explain who administered or scored it, or whether assessors remained unaware of assignment. Those details are important to interpreting the measurement process but are not reported in the registry record.

The listed intervention descriptions distinguish delivery of magnetic power output from no output through the coils. The record does not describe whether participants or assessors could distinguish the devices in practice. Therefore, the masking designation can be reported, but its success cannot be evaluated from the information recorded.

What is available for this study

The registry lists two outcome measures and zero analyses. It names a primary depression-severity measure and a secondary quality-of-life measure, but provides no numerical findings for either. The posted record therefore supports description of the intended endpoint, design, and some safety counts; it does not permit reconstruction of an effect estimate, standard error, confidence interval, or hypothesis test. In general, an analysis is most interpretable when the outcome definition, analysis population, missing-data approach, and statistical method are specified alongside the numerical estimate. Those details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary MADRS score and a secondary Q-Les-SF quality-of-life score. It does not report how many statistical comparisons were planned, whether the primary endpoint was tested at one or multiple timepoints, or how any multiple testing was addressed. A multiplicity strategy, such as prioritizing a primary comparison or adjusting inference across several tests, is not reported in the registry record. Without that information and without analysis results, the chance of false-positive findings across a set of comparisons cannot be assessed.

The primary outcome timeframe includes baseline and Week 6. The record does not state whether the intended analysis compared Week 6 scores, changes from baseline, or another contrast. Nor does it explain whether the outcome was analyzed at each timepoint separately. The statistical plan and endpoint hierarchy are not reported in the registry record.

Missing-data handling is also not described. The record does not give the number of participants with MADRS observations at each assessment, identify withdrawals or missed visits, or specify whether any method was used to address missing scores. It does not report an analysis population, such as all randomized participants or only participants with available outcome data. These omissions prevent assessment of how incomplete follow-up might affect the results.

In general, missing-data methods make assumptions about why observations are absent and about how the unobserved values relate to observed information. Different assumptions can lead to different estimates. No particular mechanism or method can be inferred for this study from the registry description. These are unreported aspects of the analysis, rather than evidence that missing data occurred or were handled in a particular way.

11. 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 0% reporting threshold.

The registry’s adverse-event listing reports that 5 participants were at risk in the active group and 7 in the inactive group. It records 0 participants affected by serious adverse events in each group and 0 affected by other adverse events in each group. These are the safety figures recorded for the stated group denominators.

The death entries are null, which means deaths are not reported in the registry record; that is different from a reported count of zero deaths. The record does not list serious adverse-event terms. It also does not provide event-level descriptions, follow-up duration, or a fuller account of how adverse events were collected, so those details are not reported in the registry record.

Zero affected participants in the posted counts does not establish that no adverse events could occur, and it does not by itself demonstrate equivalent safety between the groups. Safety interpretation depends on the number and characteristics of participants observed, the duration of observation, the way events were defined and collected, and the precision of the estimates. The record’s group counts are small, and no comparative safety analysis or uncertainty estimate is reported. These figures should be read as recorded counts, not as a definitive test of safety.

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

The record establishes that a completed randomized, quadruple-masked, parallel-group study compared active with inactive Neuronetics rTMS stimulators in an enrollment of 12. It names depression severity on MADRS as the primary outcome and lists baseline and Week 6 as the assessment timeframe. It also names a secondary quality-of-life measure. These details describe the study question and measurement plan.

The record does not report the primary outcome values or a statistical analysis. As a result, it does not show whether scores differed between groups, whether scores changed over time, or how precise any estimated difference might be. The same limitation applies to the listed secondary outcome. The absence of posted numerical results cannot be interpreted as a finding of no effect, and it cannot be interpreted as evidence of an effect.

The trial’s stated motivation concerns rTMS as an alternative treatment to ECT, but the recorded randomized comparison is active versus inactive rTMS. The study therefore does not provide a direct randomized comparison with ECT based on the arms listed in the record. The registry also says that the trial could provide data for planning a larger study if there were evidence of a clinically relevant effect. No effect estimate or numerical planning result is reported, so the record does not establish whether that condition was met.

In general, an estimate of an effect and its uncertainty are both needed for a balanced interpretation. A point estimate describes the magnitude and direction under the chosen analysis; an interval conveys how uncertain that estimate is. A significance test alone, even if reported, would not establish clinical importance. Here, no estimate, interval, or test result is available in the registry record. The supported conclusion is therefore limited to what was studied and what was recorded, rather than whether active rTMS changed depression severity.

The safety listing records 0 participants affected by serious adverse events and 0 affected by other adverse events in both groups, with deaths not reported in the registry record. Those counts should not be extended into a claim that the interventions are safe or that their risks are equal. They describe the available entries, with no comparative analysis or precision assessment reported.

13. Why This Trial Matters Statistically

Small randomized trials can have an important statistical role even when they cannot provide a precise estimate of treatment effects. They can test whether the intervention and comparator can be implemented, whether the outcome can be measured, and whether a larger study may be worth planning. The stated aim of this study included generating data to support power planning for a larger trial if there were evidence of a clinically relevant treatment effect.

For planning a later study, an observed effect estimate is only one input. Its uncertainty, the variability of the endpoint, the chosen significance level, allocation, and the effect considered important all influence the sample size needed. The registry describes planning illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Those are calculation assumptions, not a complete account of the trial’s original design rationale. The numerical illustrations and the effect fractions are not reported in the registry record.

This record also illustrates why registration details and posted results serve different purposes. The record identifies the randomized comparison, masking classification, intervention descriptions, endpoint, and timeframe. Yet without outcome estimates and an analysis description, readers cannot judge the size or precision of the primary comparison. Clear reporting of group results, participant flow, analysis populations, missing-data handling, and the statistical approach would make the evidence more interpretable.

The distinction between the stated motivation and the actual comparator is also statistically important. A study motivated by the possibility of replacing or serving as an alternative to ECT does not estimate a direct rTMS-versus-ECT contrast when its randomized arms are active and inactive rTMS. Framing the evidence according to the comparison actually randomized avoids overstating what the design can answer. In this case, the record identifies a potentially informative design question but does not report the numerical results needed to answer it.

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 registry record does not report numerical results for the primary MADRS outcome, despite listing baseline and Week 6 as the timeframe. It also does not report numerical results for the secondary Q-Les-SF outcome. The absence of group values and effect estimates prevents assessment of direction, magnitude, and precision. Zero analyses are listed, and no test results or confidence intervals are reported.

The enrollment is 12, with safety denominators of 5 in the active group and 7 in the inactive group. The record does not provide participant flow, assessment completion counts, baseline characteristics, or reasons for discontinuation. It is therefore not possible to determine from the record how many participants contributed outcome data at each assessment or whether the groups differed at baseline on important characteristics.

The primary outcome description refers to both MADRS, described as a ten-item questionnaire, and MADRS-S, described as a nine-question instrument with an overall range from 0 to 60 points. The record does not clarify which instrument version generated the outcome. It also does not explain the selected analysis contrast for the baseline and Week 6 assessments.

The statistical analysis plan, analysis population, missing-data approach, multiplicity handling, and sample-size justification are not reported in the registry record. The stated planning illustrations are described as based on the observed effect, but no numerical illustration or effect fraction is reported. The record also does not describe the details of randomization or how quadruple masking was implemented. These omissions limit appraisal of both the analysis and the conduct of the trial; they do not establish that any specific procedure was or was not used.

Finally, the randomized comparator was an inactive rTMS device, whereas the study’s stated purpose refers to ECT as an alternative treatment. The listed arms do not provide a direct randomized comparison against ECT. This limits the comparison that can be addressed from the recorded design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: rTMS in Treatment Resistant Depression — NCT02080507.
• Registry record last updated 2017-05-30; status last verified 2017-04.
• Results first posted 2017-05-30.
• 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

The registry record describes a completed, randomized, quadruple-masked, parallel-group study of active versus inactive Neuronetics rTMS for depression. Enrollment was 12. The study start is listed as 2014-03, and primary completion as 2015-12. The phase is listed as NA.

The primary outcome is depression severity assessed by MADRS, with baseline and Week 6 listed as the timeframe. A secondary outcome is quality of life assessed by the Q-Les-SF. The record lists two outcome measures and zero analyses, but does not report numerical outcome results or statistical comparisons.

Safety entries report 0 participants affected by serious adverse events and 0 affected by other adverse events in the active group, with 5 at risk; the corresponding inactive-group entries are 0, 0, and 7. Deaths are not reported in the registry record. The stated study purpose includes examining rTMS as an alternative to ECT and informing planning for a larger study if clinically relevant evidence emerged, but the recorded randomized comparison is active versus inactive rTMS.