Investigating Two rTMS Strategies to Treat Cannabis Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigating Two rTMS Strategies to Treat Cannabis Use Disorder (NCT05720312), a randomized na study. The primary outcome is Number (%) of Participants Who Started and Completed Treatment.

2. Clinical Question

3. Trial Design

NCT05720312, titled “Investigating Two rTMS Strategies to Treat Cannabis Use Disorder,” is a randomized, unmasked, parallel-group study sponsored by Stanford University. Its official title describes it as a preliminary investigation of two repetitive transcranial magnetic stimulation strategies. The phase is listed as NA, and the registry status is completed. The recorded start date is 2023-07-01, and the primary completion date is 2024-05-14.

The intervention is rTMS, a device intervention. The DLPFC group is described as receiving 36 sessions of high frequency (10Hz) stimulation; the vmPFC group is described as receiving 36 sessions of low frequency (1Hz) stimulation. The brief study summary also says participants receive a brief three-session counseling therapy alongside rTMS. The primary outcome timeframe is 6 to 9 weeks.

The registry reports enrollment of 22, while the primary outcome results list 10.0 participants in each arm. These figures describe different record entries; the registry does not explain their relationship. Allocation concealment, masking beyond the stated absence of masking, the randomization procedure, and the handling of departures from the assigned treatment are not reported in the registry record.

The primary outcome counts participants who started and completed treatment. It is therefore an indicator of treatment participation and completion, rather than a clinical-use endpoint. The record also lists several secondary outcomes, including measures of days of use, use sessions, quality of life, and a period of abstinence during follow-up. Numerical results are available for the abstinence outcome; numerical findings for the other named measures are not reported in the registry record.

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: 22 participants signed informed consent, and 20 were randomized to treatment.

Treatment Period (6 to 9 Weeks)

Follow-up Period (6 Weeks)

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 Number (%) of Participants Who Started and Completed Treatment, measured over 6 to 9 weeks.

The primary endpoint is the number and percentage of participants who started and completed treatment. The registry gives a timeframe of 6 to 9 weeks. The posted result is 8.0 of 10.0 participants in the DLPFC group and 8.0 of 10.0 in the vmPFC group.

Treatment completion is useful in a preliminary comparison because it describes whether participants reached the end of the assigned treatment course. It can provide information about the feasibility of delivering the study regimen and participants’ ability to remain engaged through treatment. It does not, by itself, establish whether marijuana use changed, whether abstinence occurred, or whether either rTMS target had a specific effect on those outcomes.

The endpoint also reflects only one aspect of participation. The record does not give the criteria for “started” or “completed,” or state how partial treatment attendance was classified. Those operational definitions are not reported in the registry record. Nor is a separate result presented for starting treatment apart from the combined started-and-completed endpoint.

For this comparison, the observed group counts are the same. The risk difference is 0.0, with a confidence interval from -0.351 to 0.351. Thus, the point estimate does not indicate a difference in completion, but the interval includes differences in either direction. The endpoint should be interpreted as a descriptive measure of treatment completion, with substantial uncertainty about the underlying contrast.

7. Results Posted in the Registry

• Ventromedial Prefrontal Cortex (vmPFC): 80.0% (8/10) versus 80.0% (8/10) on control; risk difference 0.0 percentage points (95% CI -35.1 to 35.1), risk ratio 1.00 (0.65–1.55); unadjusted two-proportion z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants Who Had a Period of 4-consecutive Weeks of Abstinence During the Follow-up Period

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ventromedial Prefrontal Cortex (vmPFC): 40.0% (4/10) versus 0.0% (0/10) on control; risk difference 40.0 percentage points (95% CI 9.6 to 70.4); unadjusted two-proportion z-test p = 0.025.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Ventromedial Prefrontal Cortex (vmPFC) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering days of use per week, average use sessions per week, quality of life, and a period of abstinence during follow-up. The numerical result available for the abstinence measure is distinct from the primary treatment-completion result: one measures a period of use behavior, while the other records whether treatment was started and completed. The registry does not report numerical findings for the other named secondary measures.

This pattern means the available secondary evidence cannot be treated as a complete account of all outcomes the registry names. In particular, the missing numerical results for use frequency and quality of life prevent a broad assessment of whether the abstinence finding coincided with changes in those measures. Their results are not reported in the registry record.

The reported abstinence comparison is potentially informative, but it carries less weight than a single prespecified primary result when its place in the analysis plan is unknown. Testing multiple outcomes creates more opportunities for an apparently notable result to arise by chance. Statistical procedures can address that issue, but the registry does not report a multiplicity strategy, a testing hierarchy, or whether the secondary outcome was designated for confirmatory inference.

The secondary result should therefore be read as an exploratory signal within a preliminary study, not as a standalone confirmation. It does not change the primary completion finding, and the two outcomes should not be combined into a single conclusion. Interpretation would be strengthened by complete reporting of all registered secondary outcomes and by an account of the planned analyses and multiplicity handling. These details are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Days of Use Per Week.
• Average Number of Use Sessions Per Week.
• Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Scale Score
• Number of Participants Who Had a Period of 4-consecutive Weeks of Abstinence During the Follow-up Period

9. Statistical Interpretation

10. Statistical Methods Explained

The registry describes a randomized, unmasked, parallel-group comparison. Random allocation is intended, in general, to make the assigned groups comparable on average, including on factors that were not measured. In a small study, randomization does not guarantee that all prognostic characteristics will be balanced. The registry does not report the allocation sequence method or whether allocation was concealed before assignment.

What does the risk difference represent?

A risk difference subtracts the event proportion in one group from the event proportion in the other, using the order specified for the comparison. For the primary endpoint, the reported risk difference is 0.0 because the posted counts are 8.0 of 10.0 in each group. A value of 0.0 is the point estimate from these data; it is not proof that the underlying groups have identical completion probabilities. The interval around the estimate is important because the observed counts come from a limited set of participants.

The primary endpoint is a binary participant-level outcome: each participant is counted according to whether they started and completed treatment. It is not a count of sessions attended or a measure of treatment response. The registry does not specify how incomplete attendance, treatment interruption, or missing completion status was classified. Those details are not reported in the registry record.

How should the p-value be read?

A p-value describes how unusual data at least as discrepant as the observed data would be under a stated statistical model and a null hypothesis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary comparison’s unadjusted p-value is 1.0. Because the observed completion counts are equal, the point estimate is zero; the p-value does not demonstrate equivalence or rule out differences that the confidence interval still allows.

The secondary abstinence comparison has an unadjusted p-value of 0.025. That value pertains to the stated secondary outcome and its comparison, without accounting for other outcome testing. A p-value is most interpretable when the hypothesis, analysis, and multiplicity approach are prespecified. Those details are not reported in the registry record.

Why does the confidence interval matter?

A confidence interval communicates uncertainty about an estimated effect. In general, a narrower interval indicates greater precision, while a wider interval leaves more plausible values unresolved. The primary risk-difference interval runs from -0.351 to 0.351, spanning both directions around the point estimate. The secondary interval runs from 0.096 to 0.704. Neither interval should be read as a guarantee about the true effect; each relies on the statistical method and assumptions used to construct it.

With binary outcomes, the uncertainty depends in part on how many participants contribute outcome information and how events are distributed across groups. When counts are small, one participant’s classification can have a noticeable influence on an estimated proportion. The primary result has equal observed proportions, but its interval remains wide. Precision, not just the point estimate or p-value, is therefore central to interpretation.

What can be said about the analysis plan?

The registry lists no reported analyses for the primary outcome and no reported analyses for the secondary outcome entries. It nevertheless posts the group counts and comparisons described in the results. The statistical analysis plan, model specification, covariate adjustment, treatment of missing data, and planned handling of multiple outcomes are not reported in the registry record. It is therefore not possible to verify from the record whether the posted comparisons follow a prespecified plan.

Sample-size illustrations, when based on an observed effect, are planning exercises rather than observed power. They describe hypothetical design requirements under stated assumptions; they do not show the probability that this completed study detected an effect. The record’s planning description specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. Such assumptions do not replace a trial-specific sample-size justification, which is not reported in the registry record.

11. Confidence Intervals and Precision

For treatment completion, the observed counts are 8.0 of 10.0 in each group, and the estimated risk difference is 0.0. The confidence interval extends from -0.351 to 0.351. This is a broad range around the point estimate: it includes a lower completion proportion for either group, as well as the possibility of no difference. The result is therefore not precise enough to identify a narrow range of plausible differences.

For the follow-up abstinence outcome, the reported risk difference is 0.4, with a confidence interval from 0.096 to 0.704. This interval is entirely above 0, but it also covers a substantial range of possible magnitudes. Its endpoints describe uncertainty in the estimated contrast, not guaranteed lower and upper limits for every population or setting.

Confidence intervals are useful because a point estimate alone can make a small study appear more conclusive than its data warrant. General statistical interpretation treats an interval as a set of values reasonably compatible with the data under the method’s assumptions. Repeated studies using the same method would not make every interval contain the true value, and the interval does not account for unreported design or analysis choices.

Both comparisons are based on small reported group counts. With binary outcomes, that limits precision, particularly when event counts are sparse. The registry does not report whether any sensitivity analyses were conducted, so the robustness of the intervals to alternative assumptions cannot be assessed from the record. The estimates should be read as uncertain comparisons from this study, rather than precise measures of a stable effect.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and several secondary outcomes. It posts a primary comparison and a numerical comparison for the follow-up abstinence outcome. The analysis strategy for the other listed secondary outcomes is not reported in the registry record. The record also does not state how many hypotheses were planned, whether some outcomes were exploratory, or whether a hierarchy controlled the order of testing.

Multiplicity matters because examining several outcomes can increase the chance of observing a small p-value even when no underlying effect exists. This general concern does not invalidate a secondary finding, but it changes how much evidential weight to place on an unadjusted p-value. The abstinence p-value is explicitly unadjusted; no adjustment for the broader set of outcomes is described. Any conclusion based on it should remain cautious.

Missing-data methods and analysis populations are also not described. The primary results list 10.0 participants in each group, while overall registry enrollment is 22. The relationship between those entries is not explained. The record does not state whether the analysis included all randomized participants, only participants with recorded outcomes, or another defined population. It also does not describe imputation, exclusion rules, or sensitivity analyses for missing outcomes.

These reporting gaps limit assessment of whether the analyses followed a prespecified plan and whether results might change under alternative missing-data assumptions. They do not establish that data were missing or that a particular analytic choice was made. The relevant handling of missing data, analysis populations, multiplicity, and prespecification is not reported in the registry record.

13. 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

For the treatment period, the registry reports zero serious adverse events among 10 participants at risk in each group. It reports 3 other adverse events in the DLPFC group and 4 in the vmPFC group. For the follow-up period, it reports zero serious adverse events and zero other adverse events among 8 participants at risk in each group. Deaths are reported as zero in both groups during treatment and follow-up.

These are event counts, not evidence that no adverse experiences occurred: the registry distinguishes serious events from other adverse events, and the other-event counts during treatment are nonzero. The record does not provide the event terms, severity details for the non-serious events, or whether events were considered related to treatment. It also does not explain the difference between the at-risk counts reported for treatment and follow-up.

Zero recorded serious adverse events in these groups should be interpreted in the context of the limited number of participants and the observation periods. Such counts cannot rule out uncommon events or establish comparative safety. The adverse-event figures describe what was recorded in this study; broader safety conclusions are not supported by these counts alone.

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

The primary result says that the same number of participants in each reported group started and completed treatment: 8.0 of 10.0. The estimated risk difference is 0.0, but its confidence interval, from -0.351 to 0.351, leaves substantial uncertainty about the underlying difference. This result does not demonstrate equivalence between the DLPFC and vmPFC strategies.

The registry also reports a difference in the observed counts for the secondary outcome of a period of 4-consecutive weeks of abstinence during follow-up. That finding is not a substitute for the primary endpoint, and its unadjusted nature and secondary status call for cautious interpretation. The record does not provide numerical results for the other named secondary outcomes, so the posted findings cannot establish a complete picture of changes in use or quality of life.

The comparison concerns two specific rTMS targets and frequencies, delivered in a study whose summary describes brief counseling alongside stimulation. It does not compare rTMS with no rTMS, counseling alone, or another treatment. The findings therefore cannot isolate the contribution of rTMS from the counseling context or support conclusions about unstudied regimens.

Nor do the results establish how the strategies would perform in populations or settings beyond this preliminary study. The registry does not report a detailed analysis plan, missing-data approach, or multiplicity procedure. The posted data support a description of the observed outcomes and their uncertainty, but not a definitive claim about effectiveness, equivalence, or comparative safety.

15. Why This Trial Matters Statistically

This trial is statistically important as a small randomized comparison of two distinct rTMS targets and frequencies, with a clearly identifiable treatment-completion endpoint. Randomization provides a useful framework for comparing groups, while the posted completion result illustrates why estimates need to be read alongside their uncertainty. Equal observed counts do not eliminate uncertainty about the underlying contrast.

The contrast between the primary and secondary outcomes also demonstrates why endpoint roles matter. Treatment completion describes engagement with the intervention; follow-up abstinence describes a use-related outcome over a specified period. They address different questions and can have different observed patterns. Keeping those interpretations separate prevents a secondary finding from being mistaken for the answer to the primary question.

The record is also a useful example of the importance of complete outcome and analysis reporting. Several secondary measures are named, but their numerical results are not reported in the registry record. Details on multiplicity, missing data, analysis populations, and the statistical plan are likewise absent. Without those details, readers cannot fully assess the scope of testing or the sensitivity of findings to analytic decisions.

Finally, preliminary studies can inform the design and interpretation of later research, but estimates from small groups are often imprecise. A planning illustration derived from an observed effect is not observed power and should not be mistaken for evidence that the study was adequately sized to answer every outcome question. The most defensible reading emphasizes the observed results, their intervals, and the limits of what the record reports.

16. 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 primary endpoint is treatment completion rather than a direct measure of cannabis use. It provides information about participation but cannot establish whether participants reduced use or achieved abstinence. The registry does not give separate results for starting treatment and completing it, or operational definitions for either status.

The primary comparison is based on 10.0 participants in each arm, and its confidence interval is broad. The secondary abstinence comparison is also based on small group counts. Consequently, both estimated contrasts remain uncertain, and the results may be sensitive to the classification of individual outcomes. The registry’s overall enrollment entry is 22, but the record does not explain its relationship to the group counts reported for the outcome.

Outcome reporting is incomplete for the measures named in the registry. Numerical findings for days of use, average use sessions, and quality of life are not reported in the registry record. The statistical plan, analysis populations, missing-data handling, and multiplicity strategy are also not reported, limiting assessment of prespecification and robustness.

The record describes an unmasked study. It does not report whether outcome assessment was blinded, how treatment adherence beyond the completion endpoint was measured, or how counseling was delivered across groups. Follow-up is described for the abstinence outcome, but the registry does not provide extended follow-up results. The adverse-event record gives counts but limited detail about event types and treatment relatedness. These constraints limit what can be inferred about outcomes, implementation, and safety beyond the reported counts.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Investigating Two rTMS Strategies to Treat Cannabis Use Disorder — NCT05720312.
• Registry record last updated 2025-05-28; status last verified 2025-05.
• Results first posted 2025-05-28.
• 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.

20. Record Summary

NCT05720312 is a completed, randomized, unmasked, parallel-group preliminary investigation sponsored by Stanford University. It compares 36 sessions of high frequency (10Hz) rTMS targeting the DLPFC with 36 sessions of low frequency (1Hz) rTMS targeting the vmPFC. The study summary describes both strategies in combination with a brief three-session counseling therapy.

The primary endpoint is the number of participants who started and completed treatment during 6 to 9 weeks. The registry reports 8.0 of 10.0 in each group, with a risk difference of 0.0 and a confidence interval from -0.351 to 0.351. A secondary follow-up abstinence result is also posted; other named secondary outcomes do not have numerical results reported in the registry record.

Interpretation is limited by imprecision and by the absence of reported details on multiplicity, missing data, analysis populations, and the statistical plan. The available results describe this study but do not establish equivalence or broad comparative effectiveness.