Transcranial Magnetic Stimulation (TMS) in Obsessive Compulsive Disorder (OCD): Mechanisms and Biomarkers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transcranial Magnetic Stimulation (TMS) in Obsessive Compulsive Disorder (OCD): Mechanisms and Biomarkers (NCT02355002), a randomized na study. The primary outcome is Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

2. Clinical Question

The study also aimed to investigate possible mechanisms of action, biomarkers, and predictors of response. Those aims are broader than the primary symptom comparison: the primary endpoint concerns a clinical rating scale, while mechanism and biomarker questions would require measures and analyses not detailed in the posted results.

The record describes assessment from baseline at week 0 to post-treatment at week 6, with assessments every 2 weeks. It also describes follow-up data at week 18 and a comparison during follow-up from week 6 to week 18. The registry record does not report numerical Y-BOCS results, an estimated difference between randomized groups, or uncertainty intervals. Therefore, the clinical question is identifiable from the design, but its answer cannot be determined from the posted results.

3. Trial Design

This was a randomized, triple-masked, parallel-group study of TMS in obsessive compulsive disorder. The registry lists the phase as NA and an enrollment of 26. Massachusetts General Hospital is listed as the sponsor. The record gives a study start of 2015-05, primary completion on 2021-10-29, and status COMPLETED.

The randomized comparison included active TMS and sham-TMS treatment. The active arm description specifies real TMS delivered with a standard, water-cooled, figure-8 shaped coil. In the sham arm, a shield in the coil blocked the magnetic field while producing a sensory experience intended to be similar to active stimulation. The study summary describes 1-Hz repetitive TMS over the pre-supplementary motor area. The registry record does not report the randomization ratio, allocation concealment procedure, detailed stimulation schedule, or the roles masked under triple masking.

The primary outcome was Y-BOCS symptom score change from baseline to post-treatment at week 6. Assessment was scheduled every 2 weeks, and the record also describes follow-up at week 18. The study description refers to efficacy comparisons over the treatment period and during follow-up. A separate open-label active TMS treatment phase is also listed, with adverse-event data reported for that phase. The registry record does not explain how participants entered that phase or how its data were incorporated into the randomized comparison.

The record lists obsessive-compulsive beliefs and total obsessive symptoms measured by the OBQ and OCI-Revised among the secondary outcomes. The analysis plan, outcome-specific analysis populations, and model used for repeated measurements are not reported in the registry record. Consequently, the design identifies the intended comparison and measurement schedule, but does not establish the exact statistical procedure used to produce an efficacy estimate.

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.

Period 1: Phase 1, Randomized-Controlled

Reasons for not completing this period:

Period 2: Phase 2 Open-Label

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Number Analyzed in Row Differs Due to Missing/Incomplete Data

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 Obsessive Compulsive Symptoms as Measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS), measured over Change in YBOCS from baseline (week 0) to post-treatment (week 6), assessed every 2 weeks. Followup phase data was measured at week 18..

The primary endpoint is obsessive compulsive symptom severity measured with the Yale-Brown Obsessive Compulsive Scale. The registry describes the Y-BOCS as a semi-structured assessment administered by a clinician. It has 10 items, each ranging from 0 (no symptoms) to 4 (extreme symptoms), for a total possible score range from 0 to 40. Higher scores indicate more severe symptoms.

The specified primary timeframe is change from baseline at week 0 to post-treatment at week 6, with measurement every 2 weeks. The record also describes follow-up measurement at week 18 and a comparison from week 6 to week 18. Change is useful for assessing whether symptom scores shifted during a defined period, while a comparison between randomized groups can help separate changes associated with assignment to active treatment from changes also seen with sham. That interpretation depends on the analysis actually used and on the amount and pattern of missing data.

The registry identifies the summary measure as a mean with standard deviation, but gives no group means, changes, between-group estimate, or confidence interval. The direction and magnitude of the observed group contrast, and its precision, are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods matter because the study collected repeated symptom scores and included a randomized comparison, follow-up, secondary outcomes, and a note about incomplete data. The registry record describes these features but does not report the analysis plan or efficacy analyses. General explanations below clarify what such methods address; they do not imply which procedures were used in this study.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable at the start of a study, on average. It supports a between-group comparison of outcomes, because differences in outcomes can be assessed in relation to assignment rather than treatment choice. Randomization does not guarantee that the groups will be identical, particularly in a modest-sized study, and it does not remove the need to report baseline characteristics, follow-up, and the analysis population. The registry identifies the study as randomized but does not report the allocation sequence, concealment procedure, or group-specific baseline information.

What does masking address?

In general, masking is intended to reduce the influence of expectations on treatment delivery, participant reports, and outcome assessment. A sham coil designed to mimic the sensory experience of active TMS provides a comparator intended to make treatment assignment less apparent. The record describes triple masking and the sham coil, but does not state which participant, clinical, or analytic roles were masked, or whether masking was assessed. The intended masking strategy should therefore be distinguished from evidence that masking was maintained.

How should repeated measurements be analyzed?

Repeated Y-BOCS assessments can describe symptom trajectories over time, but measurements from the same participant are related rather than independent. In general, an analysis can account for that within-participant correlation and estimate group differences at specified time points or across a period. Alternatively, an analysis might focus on a prespecified change score. The choice affects the estimate and the assumptions required. The record gives the baseline, week 6, and week 18 timing, along with assessments every 2 weeks, but the statistical model, time-point contrast, and handling of repeated observations are not reported in the registry record.

What does a confidence interval communicate?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of the analysis. Its width conveys precision: a wider interval indicates greater uncertainty about the size of the estimated contrast. A point estimate alone does not show that uncertainty, and a significance test alone does not show the range of plausible effect sizes. No treatment contrast or confidence interval for Y-BOCS is reported in the registry record, so neither the magnitude nor precision of the primary comparison can be evaluated.

Why can over-dispersion matter?

General statistical note: over-dispersion arises when observed variability exceeds what a chosen statistical model expects. It is especially relevant for some count-data models, where ignoring excess variability can make uncertainty appear too small. The primary endpoint in this study is a continuous score summarized as a mean and standard deviation, not a count outcome. The registry record does not report a model for the primary outcome or identify over-dispersion as an issue, so it would be inappropriate to claim that it affected this analysis.

What is the role of the planning illustration?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such calculations are hypothetical planning aids: they indicate the participant count that an assumed effect and set of design conditions would imply. They are not observed power, do not measure the probability that the study found an effect, and do not replace a reported estimate with its uncertainty. The numerical observed effect and resulting planning counts are not reported in the registry record.

The registry does not report whether any interim analyses were planned or performed, a sample-size justification for the trial, or the statistical method for the primary endpoint. These details should not be inferred from the planning assumptions, from the enrollment figure, or from the fact that the trial is marked completed.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines several outcomes, time points, or comparisons. In general, making many statistical tests can increase the chance of at least one apparently notable result by chance. A prespecified primary outcome and a clear hierarchy of secondary questions help readers distinguish the principal analysis from exploratory ones. The registry lists the Y-BOCS as primary and includes obsessive-compulsive beliefs measured by the OBQ and total obsessive symptoms measured by the OCI-Revised as secondary outcomes. It also describes repeated Y-BOCS assessments and follow-up. The registry record does not report a multiplicity strategy, a hierarchy among analyses, or which comparisons were prespecified.

The posted record identifies 3 outcome measures and 0 analyses. Thus, it does not provide statistical estimates or tests for the listed outcomes. No adjustment method, such as a procedure controlling the overall error rate across multiple tests, is reported in the registry record. Without the analysis results and a prespecified testing plan, readers cannot determine how multiplicity was handled or distinguish confirmatory findings from exploratory ones.

Missing data are an additional concern. The primary outcome description states that the number analyzed in a row differs due to missing or incomplete data. The record does not give the number analyzed by group and time point, reasons for missingness, or the method used to handle missing values. In general, complete-case analysis, imputation, and models using available repeated observations rely on different assumptions. The results can be sensitive to those assumptions, so reporting them is important.

The analysis population is also not defined beyond the note about differing row counts. The registry record does not report whether the primary comparison followed intention-to-treat principles, included only participants with particular measurements, or used another population. The effect of missingness on the estimated contrast cannot be assessed without these details and the underlying results.

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 non-serious adverse event terms

The registry lists serious adverse events separately from other adverse events. In the active TMS Phase I group, 0 serious adverse events are reported among 15 at risk, alongside 6 other adverse events among 15 at risk. In the sham-TMS Phase I group, 0 serious adverse events are reported among 11 at risk, alongside 1 other adverse event among 11 at risk. For the open-label active TMS Phase II group, the record lists 0 serious adverse events among 16 at risk and 3 other adverse events among 16 at risk. The record lists 0 deaths in each group.

These are counts as recorded, not estimates of comparative risk. They should be read within their distinct groups and phases; the open-label phase is not the randomized sham-controlled comparison. The record does not provide event descriptions, severity or relatedness for the other adverse events, collection methods, or details on whether participants could contribute to more than one phase. No serious adverse-event terms are listed. A zero count in the registry means none are reported for that group in this record; it does not establish that an event is impossible or that all safety outcomes were captured.

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

The record establishes that investigators studied active TMS against a sham control in a randomized, triple-masked, parallel design and identified Y-BOCS change as the primary clinical outcome. It also describes a treatment-period assessment and follow-up, secondary symptom measures, and aims related to mechanisms and biomarkers. These details clarify what the trial was designed to ask.

They do not establish the answer. The registry record does not report the primary outcome estimates, group-specific changes, uncertainty intervals, or statistical tests. Without those results, the magnitude and direction of the active-versus-sham contrast are unknown from the posted results. No conclusion about efficacy, equivalence, or absence of an effect follows from missing analyses. In particular, absence of a reported comparison is not the same as a comparison showing no difference.

The record also does not provide results for the secondary symptom measures, mechanisms, biomarkers, or predictors of response. Although the study aims included these topics, the listed aims alone do not show that a marker was identified or that a mechanism was established. Such claims would require reported measurements and analyses, together with enough detail to evaluate their uncertainty and potential multiplicity.

The adverse-event counts provide a limited descriptive safety record for the listed groups. They do not quantify comparative risk or supply a complete account of the nature and seriousness of non-serious events. The open-label phase should be distinguished from the randomized comparison because it does not provide the same controlled contrast.

Accordingly, the most defensible reading is that the registry records a completed trial and its planned clinical question, but does not report the results required to judge that question statistically. The design and endpoint are informative about intent; they cannot stand in for observed estimates, precision, or a transparent account of missing data and analysis choices.

13. Why This Trial Matters Statistically

This trial is statistically notable for its combination of a randomized sham-controlled comparison and repeated measurement of a clinician-rated symptom scale. The sham coil was described as producing a sensory experience similar to active TMS while blocking the magnetic field. That design addresses a central challenge in evaluating an intervention where participant experience and expectations could influence symptom reporting. Triple masking is also recorded, although the roles masked and success of masking are not reported.

The endpoint schedule raises important analytical questions. Y-BOCS was assessed every 2 weeks during the treatment period, and the record includes follow-up at week 18. Repeated measurements can show the course of symptoms, but they also require a clear definition of the primary contrast and a method that accounts for related observations within participants. The registry record does not specify that method, making it impossible to reconstruct the intended estimand from the posted information alone.

The record is also a useful illustration of the difference between a trial design and a report of trial results. It gives enrollment, endpoint definitions, timeframes, and adverse-event counts, but lists no analyses. A completed status does not supply an effect estimate, confidence interval, or missing-data explanation. Planning illustrations based on an observed effect likewise cannot replace those results or be interpreted as observed power.

For biostatistical interpretation, these omissions matter because they prevent evaluation of both the primary contrast and the credibility of any potential finding. The record shows which questions were intended to be addressed, while leaving the estimates and inferential details unavailable.

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 central limitation for interpreting this trial is that the registry record does not report an analysis of the primary Y-BOCS outcome. No group-level means, change estimates, between-group contrast, confidence interval, or test result is listed. As a result, the symptom outcome cannot be interpreted quantitatively from the posted results.

The record notes that the number analyzed differs because of missing or incomplete data, but does not report counts by arm and assessment, reasons for missingness, or a method for handling missing outcomes. It also does not define the primary analysis population. These omissions make it impossible to assess attrition, the amount of information contributing to the comparison, or sensitivity to assumptions about missingness.

The analysis plan is not reported in the registry record. The exact model, primary contrast, treatment of repeated assessments, multiplicity strategy, and any interim analyses are not described. The sample-size illustration assumptions are not a substitute for a trial-specific sample-size justification, which is not reported in the registry record. The allocation ratio and details of triple masking are also not reported.

The aims concerning mechanisms, biomarkers, and predictors are not accompanied by reported results or analytic detail. The listed adverse-event counts lack event descriptions and additional context, and data from the open-label phase should not be treated as a randomized comparison. Finally, enrollment alone does not establish the number contributing to a particular outcome analysis. Together, these gaps limit assessment of effect size, precision, robustness, and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Transcranial Magnetic Stimulation (TMS) in Obsessive Compulsive Disorder (OCD): Mechanisms and Biomarkers — NCT02355002.
• Registry record last updated 2026-02-13; status last verified 2023-05.
• Results first posted 2023-06-08.
• 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

The registry describes a completed, randomized, triple-masked, parallel study of active versus sham TMS for obsessive compulsive disorder. Enrollment was 26, and the listed phase is NA. The study summary specifies 1-Hz repetitive TMS over the pre-supplementary motor area. The primary endpoint was Y-BOCS symptom change from baseline at week 0 to post-treatment at week 6, with assessments every 2 weeks and follow-up data at week 18.

Secondary outcomes included obsessive-compulsive beliefs measured by the OBQ and total obsessive symptoms measured by the OCI-Revised. The study also aimed to investigate mechanisms, biomarkers, and predictors. The record lists adverse-event counts for active and sham Phase I groups and an open-label active Phase II group.

The posted record does not report efficacy analyses or numerical results for the primary or secondary outcomes. It notes differing analysis counts due to missing or incomplete data, but does not describe the analysis population or missing-data methods. Thus, the design and outcome definitions are available, while the treatment-effect estimates and their precision are not reported in the registry record.