Deep rTMS and Varenicline for Smoking Cessation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Deep rTMS and Varenicline for Smoking Cessation (NCT04083144), a randomized na study. The primary outcome is Point Prevalence Abstinence at the End of 12 Weeks.

2. Clinical Question

The central contrast is the added contribution of active rather than sham stimulation when both groups receive varenicline. This framing matters: the trial does not compare varenicline with no varenicline, and its primary question is not whether smoking cessation treatment in general is effective. It asks whether the active stimulation assignment is associated with a different abstinence outcome under the treatment conditions described in the registry record.

The record describes the study as a pilot exploring a combined treatment approach and states a hypothesis that active deep rTMS would improve abstinence and affect craving, cigarette consumption, and dependence severity. That statement describes the study hypothesis, not an observed result. Numerical primary-outcome results by group, and an estimate of the contrast between groups, are not reported in the registry record. The available description therefore establishes the question and outcome definition, but does not establish whether the observed data favored either assignment.

3. Trial Design

The registry record describes a randomized, quadruple-masked, parallel-group study with enrollment of 50. Its status is completed. The listed start date is 2019-08-22, and the primary completion date is 2022-09-13. The phase is recorded as NA. The sponsor is the Centre for Addiction and Mental Health.

Participants were assigned to active deep rTMS plus varenicline or sham deep rTMS plus varenicline. Both stimulation regimens are described as lasting 4 weeks, with 5 sessions/week; both varenicline regimens are described as lasting 12 weeks. The record identifies the device interventions as active and sham deep repetitive transcranial magnetic stimulation and identifies varenicline as the drug intervention. Details beyond these descriptions, including dose, adherence, treatment changes, and the masking procedures, are not reported in the registry record.

Random allocation is intended to support a fair comparison by distributing participant characteristics between assigned groups without relying on researchers to choose who receives each treatment. In a parallel design, each participant is assigned to a treatment group rather than crossing between assignments. Masking is intended to limit the influence of treatment knowledge on participants or study personnel; the registry record labels masking quadruple but does not identify which roles were masked or how masking success was assessed.

The pilot designation signals that the study investigates a combined approach, but the registry record does not report a sample-size justification or explain whether enrollment was selected for feasibility, estimation, or hypothesis testing. It also does not report recruitment details or the number of participants analyzed for the primary outcome. Enrollment alone does not tell how many participants contributed to each analysis.

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: 50 participants were enrolled, however, 8 of them were lost to follow up before randomization and therefore were not assigned to any group.

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 Point Prevalence Abstinence at the End of 12 Weeks, measured over 12 weeks.

The primary endpoint is point prevalence abstinence at the end of 12 weeks. It is measured as a count of participants meeting the endpoint. The definition combines self-report of smoking abstinence during the past 7 days with confirmation using plasma cotinine. The registry record does not report primary outcome counts by group, so the endpoint definition is available but its observed values are not.

Point prevalence abstinence captures smoking status over a specified recent period rather than establishing continuous abstinence throughout treatment. Its defined time window makes the outcome interpretable at a particular assessment, while the biochemical confirmation is intended to corroborate the self-report. Neither component alone gives a complete account of smoking behavior over the entire study period. The meaning of a point-prevalence result therefore depends on the stated assessment window and confirmation procedure.

Binary outcomes such as abstinent or not abstinent are often summarized by the number meeting the definition in each group and by a comparison between groups. A group count alone does not quantify the precision of that comparison; interpretation also requires the relevant denominators and an uncertainty estimate. Those primary-outcome results are not reported in the registry record. Secondary outcomes include dependence, expired carbon monoxide, cigarettes per day, withdrawal, urges, and abstinence measures at other specified times, but their presence does not replace the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the design of a study from the evidence produced by its results. In this trial, random allocation and masking describe how treatment assignments were organized. They do not, on their own, reveal whether active and sham stimulation produced different abstinence outcomes. The registry record describes a randomized, quadruple-masked, parallel design, but the detailed statistical analysis plan is not reported in the registry record.

What does randomization contribute?

General explanation: randomization assigns treatment without using participant characteristics or a researcher's preference to determine the assignment. It is used to reduce systematic differences between groups at the start of a study, although chance imbalances can still occur. Randomization supports a causal comparison when the analysis preserves the assignment-based comparison and when outcome measurement and follow-up are handled appropriately. The registry record does not report enough analysis detail to determine how the primary results were analyzed.

Masking has a related but distinct role. General explanation: when participants or study personnel do not know the assigned treatment, expectations or knowledge of assignment may be less likely to influence behavior, assessment, or reporting. The record labels the study quadruple-masked. Which people were masked, whether masking was maintained, and how that was evaluated are not reported in the registry record. The label therefore describes the registered design but cannot independently demonstrate that masking was successful.

How should a binary endpoint be compared?

General explanation: for a binary outcome, each participant either meets the endpoint definition or does not. A group count describes how many meet it, while the group denominator describes how many were assessed or included in that analysis. An effect estimate summarizes the contrast between groups; a confidence interval communicates the uncertainty around that estimate. A narrower interval indicates greater precision, while a wider interval indicates less precision. These are general interpretations and do not imply any particular result for this study.

The primary endpoint is a count of participants meeting the point-prevalence abstinence definition. The registry record does not report the group-specific endpoint counts or denominators, an effect estimate, or a confidence interval. It is therefore not possible to explain the observed size or precision of the primary comparison. A count of enrolled participants is not a substitute for the endpoint analysis denominator, because not all enrolled participants necessarily contribute an outcome to every analysis; the number analyzed is not reported in the registry record.

What does a p-value answer?

General explanation: a p-value evaluates how compatible observed data are with a specified null model, under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A p-value is most interpretable alongside an effect estimate, an uncertainty interval, and a clear description of the analysis. No primary-outcome p-value or test procedure is reported in the registry record.

The sample-size assumptions describe a planning illustration computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration is described as detecting a stated fraction of the observed effect. It is a planning exercise, not observed power. The effect values and resulting planning estimates are not reported in the registry record, so no sample-size figure can be stated. Such an illustration is not the same as a justification for the original enrollment; the trial’s own sample-size rationale is not reported in the registry record.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a model treats observations as less variable or more independent than they are, uncertainty estimates can be too small and statistical tests can be misleading. The relevance of over-dispersion depends on the outcome and model. The primary endpoint is described as a count of participants meeting a binary definition, but the registry record does not report the model used, any assessment of dispersion, or whether over-dispersion was considered. No claim can therefore be made that a particular model or adjustment was applied.

How should repeated outcomes be handled?

General explanation: when outcomes are measured at multiple times, measurements from the same participant are related. A suitable analysis may account for that dependence and define in advance which time point or summary is the primary target. Selecting among many times or outcomes after looking at results can increase the chance of emphasizing a chance finding. The registry record lists outcomes at several time points, but does not report the statistical approach for repeated measurements, the handling of within-participant dependence, or a complete prespecified testing strategy.

These general concepts describe what an analysis could address; they are not claims about the methods used in this study. The registry record does not report the primary comparison method, covariate adjustment, model diagnostics, missing-data method, analysis population, or multiplicity procedure. Without those details and the numerical primary results, the design and endpoint can be described, but a full statistical appraisal of the primary treatment contrast is not possible.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and 5 analyses. It includes a primary abstinence endpoint and secondary measures covering nicotine dependence, expired CO, cigarettes per day, withdrawal, urges, and abstinence at other time points. The primary outcome is described as having several categories or time points and is not reduced in the record to a single comparison. The specific primary contrast used for statistical testing is therefore not reported in the registry record.

General explanation: examining several outcomes or time points creates multiple opportunities to observe a result that appears noteworthy by chance. A statistical analysis plan may define a testing hierarchy, adjust significance thresholds, or emphasize estimation rather than repeated hypothesis tests. The registry record does not report a multiplicity adjustment or a plan for prioritizing secondary outcomes. It would be inappropriate to assume either that an adjustment was used or that none was used in analyses outside the record.

Missing-data methods and analysis populations are also important to interpretation. General explanation: if outcome status is unavailable for some participants, an analysis must specify how those missing observations are treated. Different approaches can rely on different assumptions and can affect both the estimate and its uncertainty. The registry record does not report the amount of missing primary-outcome data, the method for handling missingness, or whether the analysis followed randomized assignment or another population definition. It also does not report outcome denominators for the primary comparison.

As a result, the record supports describing the planned outcome domains and registered design, but not reconstructing the full inferential procedure. The analysis population, missing-data assumptions, and multiplicity handling are not reported in the registry record.

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 record lists serious adverse events for the active and sham groups separately. For Deep rTMS Active + Varenicline, it reports 0 serious events among 24 at risk. For Deep rTMS Sham + Varenicline, it reports 0 serious events among 18 at risk. It lists 0 deaths in each group. No serious adverse-event terms are listed.

For other adverse events, the record reports 15 affected participants among 24 at risk in the active group and 11 among 18 at risk in the sham group. These are counts, not an adjusted comparison. No percentages or comparative estimate are reported in the registry record, and none should be inferred from the counts alone. The record does not describe the event-collection window, event definitions, severity grading beyond the serious-event category, or statistical comparison.

Zero recorded serious events does not demonstrate that serious events cannot occur, nor does it establish equivalence between assignments. The group denominators and event counts describe what the registry record reports; they do not by themselves quantify the precision of a safety comparison. The number of participants contributing to safety follow-up beyond the at-risk counts, and the duration of that follow-up, are not reported in the registry record.

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

The study addresses a focused question: whether active rather than sham deep rTMS, when combined with varenicline, is associated with a difference in point prevalence abstinence at 12 weeks. It uses a defined outcome based on self-report of abstinence during the past 7 days and plasma cotinine confirmation. This design and endpoint make the intended comparison understandable.

What the available registry record does not establish is the result of that comparison. The primary outcome counts, group denominators for the endpoint analysis, effect estimate, uncertainty interval, and test result are not reported in the registry record. The study hypothesis cannot stand in for these findings. Neither the study’s completed status nor its randomized design indicates which assignment had a higher abstinence count or how precise any difference was.

The record’s adverse-event counts are descriptive. They report 0 serious events and 0 deaths in both groups, alongside the listed counts for other adverse events. These observations should not be expanded into claims that the treatments are equally safe or that serious harm is absent. The event definitions, follow-up period, and statistical safety comparison are not reported in the registry record.

The study is described as a pilot, and its enrollment is 50. That context is relevant when considering the scope and precision of the evidence, but the registry record does not report a sample-size justification or the numerical primary results. A planning illustration based on an observed effect is not observed power and does not replace the actual outcome estimate. Any planning values are useful for exploring future study designs, not for claiming that an effect was demonstrated.

Accordingly, the defensible conclusion is limited: the registry record describes a randomized masked comparison and its intended abstinence endpoint, but does not report enough primary outcome information to estimate or interpret the treatment contrast. No statement about treatment benefit or lack of benefit follows in the registry record recorded.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a clearly framed study question and a fully interpretable result. The registry record identifies randomized active and sham stimulation assignments, a common varenicline regimen, and a specific abstinence endpoint. Those features define a comparison that can be understood without conflating the effect of stimulation with a comparison of varenicline against no varenicline.

The endpoint also illustrates why measurement definitions matter. Point prevalence abstinence is tied to the past 7 days at the 12-week assessment, with self-report confirmed using plasma cotinine. It does not by itself summarize abstinence throughout treatment or follow-up. Other abstinence outcomes are listed for additional time points, making it important to identify which time point and analysis constitute the primary comparison. The registry record does not reduce the primary outcome to a single comparison.

The absence of numerical primary results is itself consequential for statistical interpretation. Design labels, hypotheses, and endpoint definitions do not show the observed treatment contrast. Without group counts and an uncertainty estimate, readers cannot assess either the direction or precision of the primary result. This is especially important when a study is described as a pilot: planning and estimation can inform later research, but a planning illustration is not evidence of observed power or a substitute for the result.

The adverse-event reporting offers a separate lesson. Counts are useful descriptions, but safety interpretation needs clear event definitions, follow-up context, denominators, and uncertainty. The record lists group-specific counts, while key details of collection and analysis are not reported. Reading the counts cautiously prevents descriptive registry entries from being mistaken for proof of equal risks or absence of risk.

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 principal limitation for interpretation is that the registry record does not report numerical results for the primary abstinence endpoint. It gives the endpoint definition and time point but not group-specific counts, endpoint denominators, an effect estimate, an uncertainty interval, or a test result. The primary treatment contrast therefore cannot be quantified from this record.

The record indicates that the primary outcome has several categories or time points and is not reduced to one comparison. The analysis plan explaining how those categories or times were handled is not reported in the registry record. A statistical plan, including the primary testing procedure, covariate adjustment, and any multiplicity strategy, is also not reported. The record lists 10 outcome measures and 5 analyses, but does not explain how results were prioritized across those outcomes and analyses.

Information needed to assess the analyzed population is not reported in the registry record. This includes the number contributing primary-outcome data, missing outcome status, the method used for missing data, and whether the analysis followed randomized assignment. The record’s enrollment of 50 does not establish the denominator for a particular endpoint analysis.

The registry record describes the study as a pilot but does not report its sample-size justification. It describes a planning illustration based on the observed effect, but its effect inputs and resulting estimates are not reported in the registry record. The details of eligibility, participant characteristics, treatment adherence, and the masking procedure are also not reported in the registry record, limiting assessment of how the enrolled group and treatment delivery relate to the intended question.

For safety, the record lists serious and other adverse-event counts, but the collection window, event definitions, and comparative analysis are not reported in the registry record. These limitations constrain interpretation of both the efficacy question and the safety description.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Deep rTMS and Varenicline for Smoking Cessation — NCT04083144.
• Registry record last updated 2024-11-04; status last verified 2024-08.
• Results first posted 2024-11-04.
• 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

NCT04083144 is a completed randomized, quadruple-masked, parallel pilot study sponsored by the Centre for Addiction and Mental Health. Enrollment is listed as 50. The study compares active deep rTMS plus varenicline with sham deep rTMS plus varenicline. Both stimulation courses are described as 4 weeks with 5 sessions/week, and both varenicline courses as 12 weeks.

The primary endpoint is point prevalence abstinence at 12 weeks, defined by self-report of abstinence in the past 7 days and plasma cotinine confirmation. The registry record does not report the numerical primary outcome results or the statistical analysis details needed to interpret a treatment contrast. It lists serious adverse-event counts of 0 in both groups and other adverse-event counts of 15 among 24 at risk in the active group and 11 among 18 at risk in the sham group. These safety counts are descriptive, and key details of their collection and analysis are not reported in the registry record.