QuitFast: Evaluating Transcranial Magnetic Stimulation as a Tool to Reduce Smoking Directly Following a Quit Attempt: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for QuitFast: Evaluating Transcranial Magnetic Stimulation as a Tool to Reduce Smoking Directly Following a Quit Attempt (NCT04159571), a randomized na study. The primary outcome is Questionnaire on Smoking Urges Administered Daily Pre TMS to Measure Craving.

2. Clinical Question

The clinical rationale in the registry emphasizes the early period after a quit attempt. It describes the first 7 days after the quit date as a critical period for longer-term cessation and cites craving and reduced executive control as possible contributors to relapse. Those statements are background rationale, not findings from this trial. The posted comparison concerns group-average craving scores over the study period; it does not, by itself, establish whether an individual stopped smoking or remained abstinent.

3. Trial Design

QuitFast, registered as NCT04159571, was a randomized, double-masked, parallel-group study sponsored by Wake Forest University Health Sciences. The registry lists the trial as completed, with a start date of 2020-08-20 and a primary completion date of 2022-11-23. Enrollment is recorded as 40. The phase is listed as NA.

Participants were assigned to real TBS or sham TBS. The intervention descriptions specify ten sessions in each group. The arm labels name the ventromedial prefrontal cortex, while the descriptions refer to the medial prefrontal cortex; the record does not clarify this difference in terminology. It also does not identify who was masked, explain how allocation was concealed, or describe whether masking was assessed.

The primary outcome was a continuous questionnaire score, reported as a mean and standard deviation. The registry says the Questionnaire on Smoking Urges was administered daily before TMS, with results collected through study completion over an average of 8 weeks. It states that individual scores were averaged per person per time point and that scores across time points and participants were averaged for each arm. The posted arm summaries include 26 participants in the real-stimulation group and 14 in the sham group for this outcome.

The registry lists a secondary biochemical outcome, urine cotinine, and posts group summaries for it. Its arm counts differ from those for the primary outcome. The record does not explain the differences in available counts or describe participant flow, exclusions, adherence, or missing observations. Detailed eligibility criteria, setting, recruitment methods, and the trial's own sample-size justification 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.

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 Questionnaire on Smoking Urges Administered Daily Pre TMS to Measure Craving, measured over Through study completion, an average of 8 weeks.

The primary endpoint is the Questionnaire on Smoking Urges (QSU), a measure of cigarette craving. The registry describes it as a 10-item questionnaire asking participants to rate agreement with statements such as wanting a cigarette at that moment. Response options range from 1 (strongly disagree) to 7 (strongly agree), and individual scores can range from 7 to 49. Higher scores represent more craving.

The QSU was administered daily before TMS. The registry says each participant's scores were averaged per time point, then scores across time points and participants were averaged within each arm. The reported outcome is therefore an arm-level mean across the recorded study period, not a count of quit attempts, a measure of abstinence, or a time-to-relapse outcome. The stated timeframe is through study completion, an average of 8 weeks.

Repeated craving assessments can describe how participants report urges during the period under study. They may be relevant to the registry's rationale about the early phase of a quit attempt, but the posted arm averages do not show each participant's trajectory or establish how craving changed over time. The record does not report a threshold for a clinically important QSU difference, nor does it explain why this endpoint was selected over other possible measures. The registry also does not report whether the primary analysis used all repeated measurements jointly or relied on the stated averaging procedure.

7. Results Posted in the Registry

• Real TBS to the vmPFC: mean 16.00 versus 12.00 on control; difference 4.00 (95% CI 0.55 to 7.45), standardized effect d = 0.60; z-test p = 0.023.

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.

Biochemical Assessment of Tobacco Use Via Quantitative Urine Screens to Detect Cotinine Level

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Real TBS to the vmPFC: mean 1,872 versus 1,374 on control; difference 498.00 (95% CI -391.22 to 1,387), standardized effect d = 0.33; z-test p = 0.272.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Real TBS to the vmPFC and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists one secondary endpoint: biochemical assessment of tobacco use using quantitative urine screens to detect cotinine. The posted outcome is a continuous mean, measured in ng/ml, with group standard deviations. This provides a biochemical measure that complements the primary self-reported craving questionnaire, but it is not the same construct. Craving scores reflect reported urges; cotinine is used as an indicator of tobacco exposure.

The secondary comparison is less conclusive statistically than the primary craving comparison: its confidence interval crosses zero and its unadjusted p-value is 0.272. This pattern does not establish that the groups are equivalent, and it does not by itself explain the primary result. The two endpoints address related but distinct questions, so consistency between them should not be assumed or required without a prespecified rationale.

Secondary outcomes generally carry less weight for a main trial conclusion when they are not the designated primary endpoint. They may be exploratory, and testing multiple outcomes can increase the chance of observing a seemingly notable result by chance. The registry does not report a multiplicity adjustment or a hierarchy for interpreting outcomes. No sponsor-reported analyses are listed, so the secondary comparison should be treated as a summary-based, unadjusted finding rather than as a confirmed adjusted analysis.

The cotinine group summaries include fewer observations than the primary outcome summaries. The registry does not explain why the available counts differ, whether samples were unavailable, or whether the reasons for missingness differed by arm. This prevents a fuller assessment of how the secondary endpoint's observed results relate to the randomized groups. No additional posted secondary endpoints or analysis results are described in the registry record.

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

• Biochemical Assessment of Tobacco Use Via Quantitative Urine Screens to Detect Cotinine Level

9. Statistical Interpretation

10. Statistical Methods Explained

The reported endpoints are continuous measures. For a continuous outcome, a group mean describes the average observed score, while a standard deviation describes how dispersed individual observations are around that average. A mean difference compares the two group averages in the units of the outcome. These summaries are informative about location and variability, but they do not show the complete distribution or the pattern of individual responses.

What does the mean difference represent?

For the primary QSU outcome, the real-TBS group mean is 16.0 and the sham-group mean is 12.0. The posted unadjusted comparison gives a mean difference of 4.0, using the sham arm as the reference and real TBS as the comparison. In this direction, a positive difference means the reported mean score is higher in the real-TBS arm. Because higher QSU scores represent more craving, the direction of the estimate is important for interpretation. The comparison is an arm-average contrast; it does not mean that each participant's score differed by the same amount.

The corresponding standard deviations are 8.0 and 3.0. A larger standard deviation indicates more observed spread in scores within that group. Standard deviations are not standard errors: the former describes variability among observations, while the latter describes uncertainty in an estimated mean. The registry does not provide individual-level data or the within-person correlation structure for repeated measurements, so those features cannot be assessed from the posted summaries.

How should the p-value be understood?

The primary unadjusted p-value is 0.023. In general, a p-value describes how compatible data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The value should be read alongside the estimated difference and its confidence interval. The registry does not report a formal analysis plan, so the precise test and its assumptions are not described in the record.

The reported comparison is an unadjusted calculation from the posted summary statistics. It is not identified as a sponsor-reported model estimate, and no reported analyses are listed. For a repeated daily outcome, a model could account for correlations among observations from the same person and for the timing of measurements. The registry does not say whether such a model was used for the posted result. The arm-level averaging described for the QSU is the available account of how scores were summarized, but it is not a complete statistical analysis specification.

Why does variability matter?

Greater spread in scores can make an estimated group difference less precise, especially when the number of observations is limited. In general, statistical uncertainty depends on both variability and the amount of information available. Repeated observations from one person are generally correlated rather than independent; treating them as independent would overstate the information if that correlation were ignored. The registry record does not state how repeated observations were handled in inferential testing, so the posted summary-based comparison should not be assumed to incorporate a repeated-measures model.

For the secondary cotinine measure, the posted means are 1872.0 ng/ml in the real-TBS arm and 1374.0 ng/ml in the sham arm. The unadjusted difference is 498.0 ng/ml, but its confidence interval includes zero and the unadjusted p-value is 0.272. A confidence interval that includes zero indicates that the data, under the calculation's assumptions, are compatible with no mean difference as well as with differences in either direction. It is not proof that the groups are identical.

What do the planning calculations mean?

The sample-size illustrations use fractions of the observed effect as planning targets. In general, detecting a smaller effect with a given power and significance level requires more participants than detecting a larger effect, because the smaller contrast is harder to distinguish from random variation. The listed values are planning illustrations under stated assumptions, not the trial's original design calculation. The trial's own sample-size justification and original design assumptions are not reported in the registry record.

Power is the probability, under a specified alternative effect and analysis model, of rejecting the null hypothesis at the chosen significance level. It is a property of a proposed design under assumptions, not a measure of whether the completed trial's observed result is true. The sample-size figures are not observed power. The posted illustrations assume two-sided testing, a significance level of 0.05, equal allocation, and a normal approximation. Their applicability depends on those assumptions and on the effect used for planning.

Finally, the randomized, double-masked designation describes intended design features, not a guarantee against bias. The registry does not provide details on allocation concealment, masking success, adherence, missingness, or deviations from assigned stimulation. Those omissions prevent a full assessment of whether the assumptions behind an unadjusted summary comparison align with the conduct and analysis of the trial.

11. Confidence Intervals and Precision

A confidence interval expresses uncertainty around an estimated group difference under the assumptions of the calculation. For the primary QSU comparison, the interval is entirely above zero. That is consistent with the positive mean difference and indicates that the estimate is not especially close to zero under this unadjusted calculation. The interval nevertheless covers a range of possible differences, rather than identifying one exact effect.

The primary interval is relatively broad in relation to the point estimate. This reflects limited precision: the observed estimate is compatible with effects of differing sizes, even though the interval does not include zero. The registry does not provide a threshold for a clinically important QSU difference, so statistical separation from zero cannot be translated into a judgment about clinical importance.

For the cotinine comparison, the confidence interval crosses zero. It therefore includes no mean difference as one value compatible with the data and calculation, while also allowing differences in either direction. This uncertainty should not be described as proof of no effect, and the result does not establish equivalence. A formal equivalence conclusion would require a prespecified equivalence margin and an analysis designed for that purpose; these are not reported in the registry record.

Confidence intervals describe uncertainty under a statistical method and its assumptions; they do not account automatically for unreported features such as missing observations, outcome selection, or multiplicity. Here, the comparisons are unadjusted calculations from posted summaries, and a detailed analysis plan is not reported. The interval estimates therefore help convey sampling uncertainty, but they cannot resolve all uncertainty about study conduct or analysis.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. The posted illustration uses two-sided testing, a significance level of 0.05, equal allocation between the two arms, and a normal approximation. It bases the target effect on a stated fraction of the observed effect. These are planning assumptions for the illustration; the trial's own original design assumptions and sample-size justification are not reported in the registry record.

For the primary craving outcome, planning for 100% of the observed effect gives 45 participants per arm for 80% power and 60 participants per arm for 90% power. Planning for 75% of the observed effect gives 79 participants per arm for 80% power and 106 participants per arm for 90% power. Planning for 50% of the observed effect gives 178 participants per arm for 80% power and 238 participants per arm for 90% power.

The corresponding illustrations for the cotinine outcome are 148 and 198 participants per arm when planning for 100% of its observed effect; 262 and 351 when planning for 75%; and 589 and 789 when planning for 50%. In each pair, the first number is for 80% power and the second is for 90% power.

In plain terms, a design with 80% power has an 80% chance of detecting the chosen effect under the stated assumptions if that effect is real; 90% power represents a higher chance under the same type of assumptions. The calculations require more participants per arm for a smaller target effect. These figures are prospective planning illustrations, not observed power for the completed trial. They should not be read as a reconstruction of the trial's original planning process.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 4.000; pooled standard deviation σ = 6.722.
2. n = 2 × (1.96 + 0.842)² × 6.722² / 4.000² = 44.3, rounded up to 45 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 4                      # observed difference in means
sigma <- 6.72192015173609                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4159571)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 45 (80% power), 60 (90% power)
 75% of observed effect: n per arm = 79 (80% power), 106 (90% power)
 50% of observed effect: n per arm = 178 (80% power), 238 (90% power)
power.t.test: 45.3 
Simulated power at n = 45 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary craving outcome and one secondary cotinine outcome, and it reports three outcome measures overall. However, it does not report a statistical analysis plan, a hierarchy among outcomes, or a procedure for controlling multiplicity. When several outcomes or analyses are examined, the chance of at least one apparently notable result can increase. Without the planned testing strategy, the role of the unadjusted p-values in the study's confirmatory interpretation is unclear.

The registry record lists no reported analyses. The available comparisons are unadjusted calculations based on the posted arm summaries. It is not reported whether the investigators planned adjustment for baseline measures, demographic or clinical covariates, repeated measurements, or any other factors. Nor is it reported whether an intention-to-treat population, a per-protocol population, or another analysis population was prespecified. Randomization is stated, but the analysis population and handling of participants after randomization are not described.

Missing-data handling is also not reported in the registry record. The primary outcome counts are 26 in the real-TBS arm and 14 in the sham arm; cotinine counts are 25 and 13. Safety denominators are different again. These varying counts indicate that the posted outcome summaries are not based on identical numbers of records across outcomes, but they do not reveal why. The record does not describe missingness patterns, imputation, sensitivity analyses, exclusions, or whether participants with incomplete daily assessments contributed to the QSU average.

Because the primary outcome involves repeated daily assessments, the analysis could depend on how incomplete measurement sequences were handled and whether within-participant correlation was accounted for. Those details are not reported. Without them, the posted summaries permit a descriptive comparison but not a full audit of the inferential procedure or its robustness to missing data and analytic choices.

15. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The safety record reports no serious adverse events in either group. The serious-event risk set is 25 for real TBS and 13 for sham TBS, with zero serious events recorded in each. Deaths are also recorded as zero in both groups. The registry lists one other adverse event in the real-TBS group and two in the sham group, with risk sets of 25 and 13 respectively.

These figures describe the events recorded in the registry and the denominators specified for safety. They should not be interpreted as proof that serious harms cannot occur, particularly because the trial's enrollment was limited and the record does not provide detailed event descriptions. The serious adverse event terms are not listed. The record also does not report severity, timing, relatedness to stimulation, or the method used to collect adverse events. The available safety summary is therefore descriptive and does not support a detailed comparison of event types or causes.

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

The posted data describe a randomized comparison of real and sham theta burst stimulation during a smoking-cessation study. The primary result is an unadjusted comparison of average craving scores: the real-TBS group had a higher mean QSU score than the sham group, and the confidence interval was above zero. The outcome's scoring direction means that higher values represent more reported craving. The secondary cotinine comparison is uncertain, with an interval that crosses zero.

These findings do not establish that stimulation changed smoking cessation success. The primary outcome measures craving, not abstinence or long-term quitting. The listed biochemical outcome is cotinine, not a posted cessation rate. The registry's background discussion of relapse and longer-term cessation is rationale for the research, not evidence that the trial measured or demonstrated those outcomes. No long-term abstinence result is reported in the registry record.

The estimates also do not show that all participants responded in the same way. Group means can conceal substantial variation, and the primary outcome's standard deviations indicate variation within both arms. The record does not provide individual trajectories, responder proportions, or a clinically meaningful threshold for interpreting the QSU difference. Statistical evidence that an average difference is above zero is not the same as evidence that its size is important to participants.

The trial is recorded as randomized and double masked, but information needed to evaluate those protections in practice is limited. The registry does not report masking details, allocation concealment, adherence, missing-data methods, or the formal analysis plan. The summary-based comparisons are unadjusted, and no reported analyses are listed. These limitations qualify the strength of conclusions that can be drawn from the posted results.

Accordingly, the most defensible reading is narrow: the observed average craving scores differed in the stated direction in the posted summaries, with uncertainty captured by the reported interval, while the cotinine comparison remains inconclusive. The registry does not establish a clinical benefit or harm, and it does not answer whether the intervention affects sustained abstinence.

17. Why This Trial Matters Statistically

This trial illustrates why the endpoint matters as much as the intervention label. Smoking cessation is a broad clinical aim, but the primary measure is a repeated questionnaire about craving. A difference in craving is not interchangeable with a difference in abstinence, relapse, or tobacco exposure. Statistical interpretation must stay aligned with what was actually measured.

It also shows how an apparently clear direction in an estimate can coexist with important uncertainty. The primary confidence interval lies above zero, but the study's posted sample is limited and the registry omits key details about analysis and missingness. The secondary cotinine comparison has a different uncertainty pattern. Neither endpoint alone resolves the broader question of long-term cessation.

For biostatisticians and clinical researchers, the record highlights the value of an explicit analysis plan for outcomes collected repeatedly over time. Clarifying the estimand, the handling of within-person correlation, missing daily assessments, outcome multiplicity, and analysis populations would make the reported estimates easier to evaluate. Reporting participant flow and reasons for changing outcome denominators would also improve transparency.

The sample-size illustrations underscore that planning depends on the effect size chosen and the design assumptions. Smaller target effects require more participants per arm under the stated framework. Because the registry does not report the trial's original sample-size rationale, the posted planning figures cannot explain why the completed study enrolled as it did. They are useful for prospective planning context, not as evidence about the completed study's power.

18. 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 are specific to this registry record. The primary outcome is summarized across daily assessments, but the record does not give the statistical model, describe how within-participant correlation was handled, or say how participants with incomplete diaries contributed. The arm counts differ across the primary and biochemical outcomes, yet the reasons are not reported. This leaves uncertainty about outcome availability and potential selection effects.

The trial is identified as double masked, but the record does not state who was masked, whether masking was successful, or how the sham procedure was designed. The intervention labels refer to the vmPFC, while the arm descriptions identify the mPFC; the record does not clarify whether these terms refer to the same intended target in this protocol. Details of stimulation parameters other than ten sessions are not reported.

The registry does not report detailed participant characteristics, inclusion and exclusion criteria, recruitment setting, adherence, allocation concealment, or participant flow. It also does not report the trial's own sample-size justification, prespecified analysis plan, multiplicity handling, or missing-data strategy. The posted comparisons are unadjusted summary-based calculations, with no sponsor-reported analyses listed.

Finally, the posted outcomes do not include a reported long-term abstinence result. Craving and urine cotinine provide information about different aspects of smoking-related behavior, but neither should be treated as a substitute for a cessation endpoint that is not reported. These gaps limit both assessment of internal validity and the scope of conclusions about smoking cessation.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: QuitFast: Evaluating Transcranial Magnetic Stimulation as a Tool to Reduce Smoking Directly Following a Quit Attempt — NCT04159571.
• Registry record last updated 2024-05-21; status last verified 2024-04.
• Results first posted 2024-05-21.
• 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.

22. Record Summary

QuitFast (NCT04159571) is recorded as a completed, randomized, double-masked, parallel-group trial sponsored by Wake Forest University Health Sciences. It compared real TBS with sham TBS. The primary endpoint was average Questionnaire on Smoking Urges score through study completion, over an average of 8 weeks. The real-TBS group had a higher posted mean score than the sham group; the unadjusted mean difference was 4.0, with an interval above zero and an unadjusted p-value of 0.023.

The registry also posts a urine cotinine outcome. Its unadjusted comparison is uncertain, with a confidence interval crossing zero. Safety summaries report no serious adverse events or deaths in either arm. The record does not report a formal analysis plan, missing-data methods, multiplicity handling, or long-term abstinence results. Interpretation is therefore limited to the posted craving and cotinine summaries and their associated uncertainty.