Accelerated rTMS for the Reduction of Nicotine Craving: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Accelerated rTMS for the Reduction of Nicotine Craving (NCT03352609), a randomized na study. The primary outcome is Tolerability Measured by Percent of Participants Completing the rTMS Course.

2. Clinical Question

The clinical question is therefore about whether participants can complete the course, rather than a direct estimate of change in craving. The study’s stated purpose was to determine whether five rTMS treatments could reduce cigarette craving. However, the posted primary outcome is tolerability, defined by completion of the course. A secondary outcome is listed as reduction in self-reported smoking; the record does not report a result for that outcome.

The record identifies a randomized, quadruple-masked, parallel-group comparison of active and sham rTMS. It lists nicotine use disorder and nicotine dependence as conditions. The active and sham groups have posted participant counts of 2 and 3, respectively. Those small counts make the information in the record highly limited: the outcome counts alone do not establish a precise comparison, and no statistical analysis is posted.

3. Trial Design

This is a randomized, quadruple-masked, parallel-group trial comparing active rTMS with sham rTMS. The phase is recorded as NA. The sponsor is the Medical University of South Carolina. The registry lists an enrollment of 5 and marks the study as terminated.

The active intervention is described as 5 rTMS sessions delivered with a MagVenture MagPro double-blind system. Each session used 3000 pulses of 10hz stimulation, delivered at 110% of resting motor threshold with 5s on and 10s off. The sham intervention used the MagPro system to mimic active rTMS and is described as 5 sessions. The record does not provide more detail about how the sham condition mimicked stimulation or how masking was assessed.

The primary endpoint is titled “Tolerability Measured by Percent of Participants Completing the rTMS Course.” Its description says the endpoint concerns completion of the 5-session course and states a hypothesis that >75% of participants would complete the 5 treatments. The posted unit and parameter describe participant counts, while the endpoint description refers to a percent. The listed arm values are counts, not percentages.

The record gives a primary-completion date of 2018-12-12 and a study start date of 2018-01-01. Its primary-endpoint timeframe is listed as “1 day (single visit),” although the intervention description concerns a multi-session course. The registry record does not explain this timeframe entry or report further design details such as eligibility criteria, recruitment procedures, or a rationale for the enrollment target.

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

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 Tolerability Measured by Percent of Participants Completing the rTMS Course, measured over 1 day (single visit).

The primary endpoint concerns tolerability, operationalized as completion of the rTMS course. Completion can serve as a practical indicator of whether participants remain in a study through the intervention, and it is distinct from a measure of craving reduction or smoking behavior. A participant who completes treatment is counted for this endpoint; the endpoint description does not explain whether completion required any additional adherence criteria.

The record’s title describes the measure as a percent, and its description says it is the percent completing the 5-session course. Yet the posted unit and parameter identify participant counts, and the active and sham arm values are reported as 2 and 3 participants. They should therefore be read as counts rather than as percentages. The record does not post a percentage value or a statistical comparison for this endpoint.

The stated hypothesis was that >75% of participants would complete the 5 treatments. This is a stated hypothesis, not evidence that the target was met. The record does not clarify the analysis population or how incomplete, missing, or partially completed courses were handled. It also labels the timeframe as “1 day (single visit),” which is not reconciled with the described course of 5 sessions. These points limit how precisely the endpoint can be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Random allocation is intended to make treatment groups comparable on average by assigning participants using a chance-based process. That purpose does not guarantee balance in a particular trial, especially when the recorded enrollment is small. The registry identifies allocation as randomized but does not report the sequence-generation method, concealment procedures, or any stratification factors.

What does masking mean in this record?

The study is labeled quadruple-masked. Masking is intended to limit the influence of treatment knowledge on participants, clinicians, outcome assessment, or other study roles, depending on the protocol. The registry does not specify which roles were masked, how masking was maintained, or whether participants or staff were asked to guess assignment. The sham condition is described as mimicking the active intervention, but the record does not provide enough detail to evaluate the success of masking.

What kind of outcome is being reported?

The primary endpoint is binary at the participant level: a participant either completes the rTMS course or does not. A count reports how many participants in a group had the event of interest. A percentage expresses that count relative to a specified denominator. Here, the endpoint description refers to a percentage, but the posted arm values are participant counts. The registry does not report a percentage or explain the denominator used for any percentage-based analysis.

For a binary endpoint, a comparative analysis could estimate the difference or ratio between groups, with an uncertainty interval, using a method suited to the data and design. The choice of method matters because different approaches can behave differently when counts are sparse. No comparative estimate, interval, or test is posted, and the registry says the values were missing or not estimable for a two-arm comparison. No particular alternative method can be attributed to the investigators from this record.

Why does uncertainty matter?

A point estimate alone would not show how much uncertainty surrounds a treatment comparison. A confidence interval, in general, describes the range of effect estimates consistent with the observed data under the method’s assumptions. With limited observations, intervals for binary outcomes can be wide, and standard approximations may be unreliable. The registry reports no interval, so readers cannot assess precision from an inferential summary. The participant counts should not be treated as evidence of a precise or stable group difference.

A p-value, in general, measures how unusual the observed data would be under a specified null hypothesis and analysis model. It does not measure the probability that a treatment effect is real, nor does it describe effect size or precision. No p-value or specified null hypothesis is reported for the primary outcome. The absence of a reported test should not be interpreted as a finding of no difference.

What is the role of the stated threshold?

The endpoint description states a hypothesis that >75% of participants would complete the treatments. This is a benchmark stated in the registry, not a result. To evaluate it statistically would require a reported numerator, denominator, analysis population, and an approach to uncertainty. The record does not post an analysis against the threshold. A raw count cannot establish whether a percentage-based hypothesis was supported without knowing how the percentage was calculated and how missing outcomes were handled.

How should the course-completion outcome be understood?

Completion is a tolerability-related measure of whether participants finish the intervention course, but it is not itself a direct measure of craving, smoking reduction, or a specific adverse event. The secondary outcome is reduction in self-reported smoking, but no result for it is posted. The record lists 3 outcome measures and zero analyses; it identifies 1 secondary outcome as posted. It does not specify the other outcome measures in the registry record in the registry record.

The listed timeframe, “1 day (single visit),” does not obviously align with the described 5-session course. The registry record does not explain whether the timeframe refers to assessment timing, an administrative entry, or another feature of outcome collection. Readers should not infer a schedule beyond what is stated.

What cannot be inferred from planning illustrations?

Planning sample sizes, when available, describe hypothetical requirements under stated assumptions; they are not observed outcomes and are not a measure of the study’s observed power. The registry record does not report the sample-size justification, assumptions used in the original design, or whether any planned calculations were revised. The treatment effect used for any planning illustration and its relationship to this small trial’s observed counts should not be interpreted as confirming an effect. A post hoc calculation cannot substitute for a prespecified analysis or an uncertainty estimate.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Active rTMS", "Sham")
n      <- c(2, 3)
events <- c(2, 3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Active rTMS  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Sham  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, identifies 1 secondary outcome as posted, and reports zero analyses. The listed secondary outcome is reduction in self-reported smoking. No result for that secondary outcome appears in the record details, and the other outcome measures are not described. The registry record does not report a statistical plan for handling multiple outcomes or multiple comparisons. Without such a plan and without analysis results, it is not possible to assess how outcome selection or multiplicity was addressed.

Missing-data handling is also not reported in the registry record. There is no description of whether every participant had an observed primary outcome, how incomplete courses were classified, whether follow-up data were available, or whether any imputation or sensitivity analysis was used. The fact that the primary outcome is described as course completion does not, by itself, establish how missing status was treated.

The record does not specify the analysis population: for example, whether the posted values include everyone randomized, only participants who began treatment, or another group. It also does not report exclusions, withdrawals, or a participant-flow account. The listed arm counts and outcome counts are therefore descriptive entries whose relationship to the intended analysis population is not explained.

No interim analyses, prespecified statistical methods, multiplicity adjustment, or sensitivity analyses are reported in the registry record. These omissions prevent evaluation of how the investigators intended to control false-positive findings, handle incomplete observations, or assess robustness. They should be treated as unreported information, not evidence that a particular procedure was or was not used.

12. 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 adverse-event record lists serious adverse events affecting 0 participants in active rTMS and 0 in sham. It lists other adverse events affecting 1 participant in active rTMS and 1 in sham. Deaths are recorded as 0 in both groups. These are counts, not rates, and the record does not provide a statistical comparison or uncertainty interval for safety outcomes.

The numbers at risk for serious adverse events are listed as 2 for active rTMS and 3 for sham. The numbers at risk for other adverse events are also listed as 2 and 3, respectively. The registry does not define the collection period or provide further detail about event ascertainment. It lists no top serious adverse-event terms.

Zero recorded serious events means that no serious events are listed for these groups in this record; it does not establish that the risk is absent. Small participant counts make safety estimates imprecise, and the registry does not provide a method for quantifying that uncertainty. “Other” adverse events should not be interpreted as a specific event type because no terms are listed for them. These counts describe what is posted, not a complete assessment of safety or a basis for clinical advice.

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

The posted results document participant counts for the primary completion outcome and adverse-event counts in each treatment group. They also document that the trial was terminated and that its registry record contains no reported statistical analyses. Taken together, these entries describe what was recorded, but they do not provide a precise estimate of the comparative effect of active versus sham rTMS on course completion.

The study’s stated purpose concerned reduction in cigarette craving, while its primary endpoint concerns completion of the rTMS course. Those are different questions. Course completion may inform tolerability, but it does not establish whether craving changed. The record lists reduction in self-reported smoking as a secondary outcome without a posted result. No conclusion about craving or smoking reduction can be drawn from the primary counts alone.

The record’s completion hypothesis uses a threshold of >75%, but the posted arm entries are counts and no analysis against that threshold is reported. The registry also does not explain missing outcome handling, the analysis population, or whether all participants contributed to the primary endpoint. These gaps mean that even a descriptive comparison must be read cautiously, and a formal claim of a difference, similarity, or equivalence is unsupported by the posted statistical results.

The absence of an inferential analysis is not evidence that the groups are the same, nor is it evidence that one intervention is better. No medical conclusion follows from the counts. The study offers a small, terminated record with limited outcome reporting; interpretation should remain confined to the values and limitations documented in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why a clear link between the research question, endpoint definition, and analysis matters. The stated study purpose concerns cigarette craving, while the primary endpoint is course completion as a tolerability measure. Completion is a relevant study outcome, but it does not answer the same question as a direct measure of craving or smoking behavior. The record lists a self-reported smoking outcome as secondary but does not post its result.

The endpoint description calls completion a percentage, while the posted arm values and units are counts of participants. This distinction is important: a count does not communicate a percentage unless its denominator and calculation are stated. The registry does not post percentages or a comparison, and it identifies the two-arm binary analysis as missing or not estimable. Clear reporting of the endpoint scale, denominator, and analysis would make the result easier to interpret.

The trial also demonstrates why uncertainty is central to reading a group comparison. Participant counts can describe the observed data, but without an effect estimate and uncertainty interval, they do not show how precisely an active-versus-sham difference has been estimated. The record’s small enrollment and lack of inferential results make strong comparative interpretation inappropriate.

Finally, the status is terminated, but the record does not state why. That information could be important for understanding the completeness of recruitment, outcome collection, and analysis, yet it is not reported in the registry record. The statistical lesson is not about the success or failure of rTMS; it is about the limits of interpreting a trial when the endpoint, denominators, analysis population, missing-data handling, and uncertainty are incompletely documented.

15. 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.

Several limitations specific to this trial restrict interpretation. The registry lists an enrollment of 5 and arm counts of 2 for active rTMS and 3 for sham. These limited counts cannot support precise conclusions about comparative completion or uncommon adverse events. The registry does not provide confidence intervals, a p-value, or another inferential result for the primary endpoint.

The primary outcome is described as a percentage, but the posted values are participant counts. The record does not explain a percentage calculation or provide a denominator beyond the arm counts. The stated hypothesis of >75% completion is not accompanied by a posted test or estimate. The primary timeframe is “1 day (single visit),” while treatment is described as a 5-session course; the record does not reconcile this difference.

The registry does not report why the study was terminated, whether outcome collection was complete, or how missing data and withdrawals were handled. It does not define the analysis population or provide a participant-flow account. Its skip note says the two-arm binary comparison was missing or not estimable, and it lists zero analyses. These omissions leave the basis for the posted counts and any intended comparison unclear.

The trial’s stated purpose involves craving reduction, yet the primary endpoint measures course completion. The secondary outcome concerning self-reported smoking has no reported result. Further design information—including eligibility details, randomization procedures, masking roles, and a statistical analysis plan—is not reported in the registry record. These limitations mean the posted data can be described but cannot establish a treatment effect on craving, smoking, or comparative tolerability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Accelerated rTMS for the Reduction of Nicotine Craving — NCT03352609.
• Registry record last updated 2019-10-15; status last verified 2019-10.
• Results first posted 2019-10-08.
• 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.

19. Record Summary

The registry record describes a randomized, quadruple-masked, parallel-group trial of active versus sham rTMS for nicotine dependence and nicotine use disorder. It lists an enrollment of 5, a start date of 2018-01-01, a primary-completion date of 2018-12-12, and a terminated status. The primary outcome concerns completion of the 5-session course.

Posted primary-outcome values are 2 participants for active rTMS and 3 for sham. The record does not report a statistical comparison, and it identifies the two-arm binary comparison as missing or not estimable. The secondary outcome is reduction in self-reported smoking, with no result reported. Serious adverse events and deaths are recorded as 0 in each group; other adverse events are recorded for 1 participant in each group.

The registry does not report why the study was terminated, how missing data were handled, or the analysis population. The posted results are descriptive and do not establish a comparative effect.