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 Biomarkers in Repetitive Transcranial Magnetic Stimulation (rTMS) for Adolescent Depression (NCT03363919), a randomized na study. The primary outcome is Total Children's Depression Rating Scale, Revised (CDRS-R) Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03363919 |
| Phase | NA |
| Condition | Major Depressive Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 47 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents with Major Depressive Disorder were the population of interest. The registry summary says researchers aimed to study rTMS and whether measures of brain activity could help identify patients who might benefit from different rTMS treatments. It does not report further eligibility criteria or a more detailed description of the participants included in the primary outcome analysis.
Intervention
The intervention was 10 Hz rTMS applied to the left prefrontal cortex. The arm description specifies 36 sessions, each with 2400 pulses delivered at 120% motor threshold, using 4 seconds on and 36 seconds off. The registry lists NeuroStar TMS Therapy® System and NeuroStar XPLOR® as device interventions; it does not map each device to a particular arm.
Comparator
The comparison group received 1 Hz rTMS at the left prefrontal cortex. Its regimen was 36 sessions, each consisting of 2400 continuous pulses at 120% motor threshold. This is an active rTMS protocol, not a no-treatment or placebo comparator. The registry identifies this arm as the control for the posted outcome.
Primary question
The posted primary outcome is the Total Children’s Depression Rating Scale, Revised (CDRS-R) score at 6 weeks. The outcome summaries describe each arm separately. They do not, on their own, provide a direct statistical test of the difference between the protocols. The registry’s stated broader interest also includes whether measures of cortical excitability and inhibition can identify which patients benefit from different rTMS treatments; the posted primary outcome summaries do not answer that biomarker question.
3. Trial Design
The registry describes a randomized, double-masked, parallel-group trial. Participants were assigned to one of two active left prefrontal rTMS protocols: 1 Hz or 10 Hz. The registry lists an enrollment of 47 and a completed status. The phase is recorded as NA. Mayo Clinic is named as the sponsor.
The 1 Hz arm description specifies 36 sessions at 120% motor threshold, with 2400 continuous pulses in each session. The 10 Hz arm also specifies 36 sessions at 120% motor threshold and 2400 pulses per session, delivered in intervals of 4 seconds on and 36 seconds off. These details describe the regimens recorded in the registry; additional information about treatment delivery or adherence is not reported in the registry record.
The primary outcome timeframe is 6 weeks. Its posted arm summaries include 22 participants for the 1 Hz arm and 19 for the 10 Hz arm. The registry says data were not collected or analyzed for 1 subject in the 1 Hz arm and 5 subjects in the 10 Hz arm. Those outcome counts therefore should not be taken as a complete account of trial enrollment or as a description of the analysis population beyond the specific posted outcome.
The registry gives a start date of 2018-09-24 and a primary completion date of 2023-03-03. It does not report the allocation procedure in detail, the masking procedures, or whether treatment assignment was concealed from particular study personnel. The available record identifies the design categories but does not establish further design features.
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.
Overall Study
| Stage | 1 Hz Left Prefrontal rTMS | 10 Hz Left Prefrontal rTMS |
|---|---|---|
| STARTED | 23 | 24 |
| COMPLETED | 22 | 19 |
| NOT COMPLETED | 1 | 5 |
Reasons for not completing this period:
| Reason | 1 Hz Left Prefrontal rTMS | 10 Hz Left Prefrontal rTMS |
|---|---|---|
| Withdrawal by subject - did not receive allocated intervention | 0 | 1 |
| Withdrawal by subject - discontinued intervention prior to week 1 | 1 | 4 |
Analysis population for the primary outcome, as defined in the registry: Data was not collected or analyzed for one subject in the 1 Hz arm and five subjects in the 10 Hz arm
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.
Population: 1 subject in the 1 Hz arm and 5 subjects in 10 hz arm were excluded in the analysis population due to subject withdrawal.
| Characteristic | Unit | 1 Hz Left Prefrontal rTMS | 10 Hz Left Prefrontal rTMS | Total |
|---|---|---|---|---|
| Participants analysed | 22 | 19 | 41 | |
| Age, Continuous | years | 15.68 (SD 1.83) | 15.89 (SD 1.05) | 15.78 (SD 1.51) |
| Sex: Female, Male: Female | Participants | 13 | 12 | 25 |
| Sex: Female, Male: Male | Participants | 9 | 7 | 16 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 20 | 16 | 36 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 4 | 1 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 17 | 17 | 34 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 22 | 19 | 41 |
6. Primary Endpoint
The registry lists the primary outcome as Total Children's Depression Rating Scale, Revised (CDRS-R) Score, measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Geometric Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the Total Children’s Depression Rating Scale, Revised (CDRS-R) score at 6 weeks. The registry describes the CDRS-R as a 17-item scale, with item ratings ranging from 1 to 5 or 1 to 7 and a possible total score from 17 to 113. A clinician rates the scale through interviews with the child and parent. It is used to quantify depressive symptoms in children and adolescents through a structured clinician assessment.
The registry notes that a score of 40 or higher is indicative of depression and that a score of 28 or lower is often used to define remission, described as minimal or no symptoms. These are interpretive thresholds recorded for the measure; they do not determine the meaning of a particular trial result without considering the trial population, timing, and analysis.
For this outcome, results are reported as geometric least-squares means with 95% confidence intervals. The registry does not explain the model or transformation used to produce that parameter. The posted summaries are arm-specific endpoint values, not changes from baseline, and the registry record does not report baseline CDRS-R values alongside them. The endpoint therefore describes the recorded score at the stated follow-up, while the arm summaries alone do not establish a treatment contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At 6 weeks, the posted geometric least-squares mean CDRS-R score was 41.77 for the 1 Hz arm, with a 95% confidence interval from 40.03 to 43.5. For the 10 Hz arm, the corresponding estimate was 44.54, with a 95% confidence interval from 42.63 to 46.45. The registry reports these as separate summaries for the two arms.
These estimates describe endpoint scores, not the amount of change from participants’ starting scores. Baseline values are not reported with the primary outcome, and the registry does not post a numerical between-arm estimate, confidence interval for a contrast, or statistical test for this endpoint. A direct claim about the difference between treatment protocols cannot be established from the two arm summaries alone. In particular, the displayed confidence intervals describe uncertainty around the separate estimates; they are not a substitute for an interval or test for the between-arm contrast.
In general, a confidence interval conveys the precision of an estimate under the assumptions of the analysis used to calculate it. A narrower interval indicates greater precision than a wider interval for the same kind of estimate, but precision is not the same as clinical importance. The interval also does not by itself establish whether an observed arm difference is statistically persuasive. Interpreting a treatment contrast requires an analysis that directly estimates that contrast and accounts for the trial’s design and analysis plan.
The CDRS-R description includes interpretive thresholds: scores of 40 or higher are indicative of depression, and scores of 28 or lower are often used to define remission. The arm estimates and their intervals are reported as scores. They do not indicate how many participants crossed either threshold, and no such counts are reported in the registry record. A group summary also cannot show how outcomes varied among individual participants.
The trial’s stated broader interest includes whether measures of cortical excitability and inhibition can help identify which patients benefit from different rTMS protocols. The registry lists change in Intracortical Facilitation (ICF) as a secondary outcome. The primary CDRS-R summaries do not answer whether a biomarker predicts response or whether biomarker-based treatment selection is useful.
The record is marked completed, but completion does not fill gaps in the statistical reporting. No analysis record is posted for the primary outcome, and the registry does not report the statistical model, covariate adjustment, or a direct inferential comparison. The estimates should therefore be read as the posted arm-level results, with the stated precision, rather than as a complete account of comparative effectiveness.
9. Statistical Methods Explained
The registry reports a geometric least-squares mean for the primary outcome in each arm and gives a 95% confidence interval. It does not identify the model, transformation, covariates, or estimation procedure used. Interpretation should stay with the reported parameter rather than assuming a particular statistical model from its label.
What does a confidence interval describe?
In general, a confidence interval communicates uncertainty around an estimated quantity under the assumptions of the method used to calculate it. It gives a range of values compatible with the data and method at the stated confidence level. It is not a range containing most individual participants’ scores, and it does not directly give the probability that a fixed parameter lies inside this particular interval.
The intervals reported for the CDRS-R are attached to each arm’s estimate. They do not estimate the difference between arms. A comparative analysis would ordinarily report an effect estimate for the contrast and its uncertainty, or a test of that contrast. Neither is posted for this primary outcome. Consequently, the arm summaries cannot be treated as a formal test of whether the protocols differ.
Why does the type of estimate matter?
A least-squares mean is an estimate produced within a statistical analysis, rather than necessarily being the simple arithmetic average of the observed scores. The registry calls the reported parameter a geometric least-squares mean, but does not provide enough methodological detail to explain how it was derived. No claim about covariate adjustment, back-transformation, or the model’s distributional assumptions can be made from the record alone.
In general, the interpretation of a model-based estimate depends on the model and analysis population. For example, choices about how to handle repeated measurements, missing outcomes, or other covariates may affect an estimate. The registry record does not describe those choices for this outcome. It also does not report a change-from-baseline estimate, so the values should not be described as changes in symptoms.
What can be inferred from the posted arm summaries?
The values support a descriptive account of the CDRS-R score estimates at 6 weeks in each arm, along with their reported precision. They do not identify the treatment effect of one protocol relative to the other. Separate arm estimates can be informative about outcome levels, but an inferential comparison requires an analysis of the contrast. That analysis may account for design and participant-level information unavailable in the arm summaries.
In general, an analysis should follow its prespecified plan, including the outcome definition, time point, analysis population, and approach to missing values. The registry does not report a detailed statistical analysis plan for the primary outcome. It is therefore not possible to determine from the registry whether the posted arm estimates follow a prespecified model or whether other planned analyses were performed.
How should planning calculations be read?
Any sample-size calculations based on the observed effect are planning illustrations, not observed power. The registry’s stated assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations explore the sample size that could be needed under those assumptions; they do not show the probability that this completed trial detected an effect, and they are not evidence that a treatment effect exists.
In general, planning calculations are sensitive to assumptions about the target effect, variability, significance level, allocation, and analysis method. Calculations based on an effect observed in a trial can be especially dependent on that estimate. The registry says the illustration is not the trial’s own design. Its original sample-size justification and design assumptions are not reported in the registry record.
The registry also identifies an additional outcome, change in Intracortical Facilitation (ICF), and indicates 2 outcome measures. It posts no analysis records. No statistical tests, multiplicity adjustments, or model details for the secondary outcome are reported. The general statistical concepts do not establish which methods were actually used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the CDRS-R score as the primary outcome and change in Intracortical Facilitation (ICF) as a secondary outcome. It also records 2 outcome measures, but posts 0 analysis records. The registry record does not report a statistical plan specifying how primary and secondary outcomes, multiple time points, or other possible analyses were prioritized or adjusted for multiplicity. It is therefore not possible to determine how the risk of false-positive findings across analyses was addressed.
For the primary outcome, the registry states that data were not collected or analyzed for 1 subject in the 1 Hz arm and 5 subjects in the 10 Hz arm. The posted CDRS-R summaries list 22 participants in the 1 Hz arm and 19 in the 10 Hz arm. The registry does not report why outcome data were unavailable, whether the missingness was related to participant characteristics or outcomes, or how missing data were handled in the analysis.
In general, missing outcomes can affect the interpretation of a comparison, particularly if the availability of data is related to participants’ outcomes. Methods such as imputation or likelihood-based approaches rely on assumptions that should be described and assessed. The registry does not identify whether any such method was used, whether participants were analyzed according to randomized assignment, or which analysis population was used. The posted summaries should not be taken as evidence of a particular missing-data method or analysis population.
The registry record also does not report an interim analysis plan, stopping rule, or prespecified approach to multiple comparisons. The absence of these details in the record does not establish what was or was not done outside the posted information; it means those methods cannot be evaluated from the registry record.
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 |
|---|---|---|---|
| 1 Hz Left Prefrontal rTMS | 3 | 23 | 13.0% |
| 10 Hz Left Prefrontal rTMS | 3 | 24 | 12.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 1 Hz Left Prefrontal rTMS | 0 of 23 |
| 10 Hz Left Prefrontal rTMS | 0 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 1 Hz Left Prefrontal rTMS | 20 of 23 |
| 10 Hz Left Prefrontal rTMS | 21 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | 1 Hz Left Prefrontal rTMS | 10 Hz Left Prefrontal rTMS |
|---|---|---|---|
| blurred vision | Eye disorders | 1 of 23 | 0 of 24 |
| suicidal ideation | Psychiatric disorders | 0 of 23 | 1 of 24 |
| severe scalp pain | Nervous system disorders | 0 of 23 | 1 of 24 |
| left ear bleeding | Ear and labyrinth disorders | 0 of 23 | 1 of 24 |
| chest pain | Cardiac disorders | 1 of 23 | 0 of 24 |
| groin pain | Reproductive system and breast disorders | 1 of 23 | 0 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 1 Hz Left Prefrontal rTMS | 10 Hz Left Prefrontal rTMS |
|---|---|---|---|
| Pain or Discomfort at Treatment site | General disorders | 12 of 23 | 15 of 24 |
| Headache | Nervous system disorders | 11 of 23 | 12 of 24 |
| Auditory | Ear and labyrinth disorders | 3 of 23 | 4 of 24 |
| Dizziness | Nervous system disorders | 3 of 23 | 4 of 24 |
| Sedation | Nervous system disorders | 2 of 23 | 4 of 24 |
| Twitching during treatment | Nervous system disorders | 1 of 23 | 5 of 24 |
| Insomnia | Psychiatric disorders | 3 of 23 | 2 of 24 |
| Nausea | General disorders | 1 of 23 | 4 of 24 |
| Suicidal Ideation | Psychiatric disorders | 2 of 23 | 2 of 24 |
| Anxiety | Psychiatric disorders | 0 of 23 | 1 of 24 |
Serious events with the highest arm-level rate: blurred vision (4.3%), chest pain (4.3%), groin pain (4.3%), suicidal ideation (4.2%), severe scalp pain (4.2%).
The registry reports serious adverse event counts separately for each arm. In the 1 Hz arm, 3 participants were affected among 23 at risk. In the 10 Hz arm, 3 participants were affected among 24 at risk. It reports 0 deaths in each arm. These are the serious-event figures posted in the registry; they do not by themselves establish whether an event was caused by treatment.
For other adverse events, the registry reports 20 affected among 23 at risk in the 1 Hz arm and 21 affected among 24 at risk in the 10 Hz arm. These counts are distinct from the serious adverse event counts and should be read using the registry’s separate categories. The record does not provide further detail about event duration, severity grading, timing, or whether individual participants had more than one event.
The registry lists the following serious adverse event terms and percentages: blurred vision, 4.3%; chest pain, 4.3%; groin pain, 4.3%; suicidal ideation, 4.2%; severe scalp pain, 4.2%; and left ear bleeding, 4.2%. The record does not specify in this list how terms map to arms, or provide enough detail to infer comparative risk from these percentages. Adverse event counts describe events recorded during the trial; without further context, they should not be interpreted as proof of causation or as a complete safety assessment.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry contains arm-specific CDRS-R estimates at 6 weeks for two active rTMS protocols. The 1 Hz arm estimate is 41.77, with a 95% confidence interval from 40.03 to 43.5. The 10 Hz arm estimate is 44.54, with a 95% confidence interval from 42.63 to 46.45. The summaries provide information about the recorded endpoint and the precision of those estimates.
They do not establish that one protocol is superior, equivalent, or different from the other. No direct between-arm estimate or test is posted for the primary outcome. Nor do the summaries show how much participants’ scores changed, because baseline scores are not reported alongside these endpoint estimates. They also do not show the distribution of individual responses or the number of participants meeting a particular CDRS-R threshold.
The trial’s stated research interest extends beyond symptom scores to measures of cortical excitability and inhibition, including the potential for these measures to identify which patients benefit from different rTMS treatments. The listed secondary outcome is change in ICF. The registry does not post an analysis establishing a relationship between a biomarker and outcome, or whether biomarker measures distinguish participants who benefit from one protocol rather than the other.
In general, a completed randomized trial can provide useful evidence when its outcomes, analysis populations, missing-data methods, and comparative estimates are reported in sufficient detail. The registry record does not provide many of these details for this outcome. The results should therefore be interpreted as posted summaries, not as a complete inferential analysis or a definitive answer to the broader research question.
These statistics are a description of trial data and their reported uncertainty. They are not medical advice and do not determine an appropriate treatment choice for an individual.
13. Why This Trial Matters Statistically
This trial is statistically notable because it compares two active rTMS regimens within a randomized, double-masked, parallel-group design. An active comparator makes the central question a comparison between treatment protocols rather than a comparison with no treatment. For that comparison to be evaluated statistically, arm-level estimates need to be accompanied by a direct contrast and its uncertainty, with methods suited to the design and outcome.
The registry posts geometric least-squares mean CDRS-R scores and 95% confidence intervals for each arm at 6 weeks. These summaries make the endpoint and its reported precision visible, but they are not a direct treatment-effect estimate. The distinction matters: separate estimates answer what was recorded in each arm, while a contrast addresses how the arms compare under the specified analysis.
The registry’s broader question about biomarkers adds another statistical challenge. A biomarker may be associated with outcomes without identifying which treatment is more suitable for a particular participant. Evaluating treatment selection requires analysis of how biomarker measurements relate to outcomes across treatment assignments, and clear reporting of the relevant models and uncertainty. The posted primary outcome summaries alone cannot answer that question.
Missing outcome data also matter to interpretation. The registry notes unavailable or unanalyzed data for some participants in both arms, but does not describe the reasons or handling method. Transparent reporting of missingness and analysis populations is important for judging how well the estimates represent the randomized groups.
More complete reporting of the comparative analysis, statistical plan, and biomarker results would be needed to assess these questions fully. The record’s arm summaries remain useful descriptive information, but they do not resolve the trial’s comparative or biomarker aims on their own.
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 provide a direct statistical comparison of the primary outcome between the two arms. It reports arm-level estimates and confidence intervals only. The model used to produce the geometric least-squares means, any covariates, and the analysis population are not reported in the registry record.
The primary outcome summaries concern scores at 6 weeks. Baseline CDRS-R values and change-from-baseline estimates are not reported with these results, so the endpoint values cannot be interpreted as within-participant change. The registry also does not report counts of participants who met the scale’s stated thresholds or a distribution of individual outcomes.
Data were not collected or analyzed for 1 subject in the 1 Hz arm and 5 subjects in the 10 Hz arm. Reasons for missing outcome data and the handling approach are not reported in the registry record. Without this information, the potential influence of missingness on the estimates cannot be assessed.
The trial’s stated interest includes biomarkers, but no biomarker analysis is posted. The registry lists change in ICF as a secondary outcome, while posting 0 analysis records. The statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. The planning illustration is not the trial’s own design and should not be treated as observed power.
Finally, the registry describes two device interventions but does not map each named device to a specific arm. It also does not provide further detail about eligibility, adherence, masking procedures, or reasons for discontinuation. These limits constrain assessment of implementation and the context of the posted outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Biomarkers in Repetitive Transcranial Magnetic Stimulation (rTMS) for Adolescent Depression — NCT03363919.
- Registry record last updated 2024-02-01; status last verified 2024-01.
- Results first posted 2024-02-01.
- 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
NCT03363919 is a completed randomized, double-masked, parallel-group trial sponsored by Mayo Clinic. It enrolled 47 participants and compared 1 Hz with 10 Hz rTMS applied to the left prefrontal cortex in adolescents with Major Depressive Disorder. The registry records the phase as NA.
The primary outcome was the Total Children’s Depression Rating Scale, Revised (CDRS-R) score at 6 weeks. The registry posts a geometric least-squares mean and 95% confidence interval for each arm, but no direct between-arm test or estimate. It states that data were not collected or analyzed for 1 subject in the 1 Hz arm and 5 subjects in the 10 Hz arm. Change in Intracortical Facilitation is listed as a secondary outcome, and no analysis records are posted.
The registry lists serious and other adverse event counts, with 0 deaths in each arm. The trial start date is 2018-09-24 and the primary completion date is 2023-03-03. Details of the statistical model, missing-data handling, and analysis populations are not reported in the registry record.