Targeted Pharmacological and Behavioral Treatments for Smoking in Schizophrenia Study 1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeted Pharmacological and Behavioral Treatments for Smoking in Schizophrenia Study 1 (NCT03507127), a randomized phase 2 study. The primary outcome is Questionnaire on Smoking Urges - Brief Form.

2. Clinical Question

3. Trial Design

The registry describes a phase 2, randomized, double-masked, parallel study comparing varenicline with placebo. It records enrollment of 5 and a terminated status. The study start date is 2018-05-01, and the primary completion date is 2019-06-30. The reason for termination and any effect it had on recruitment or follow-up are not reported in the registry record.

The study description outlines a sequence of study activities. Participants first completed a baseline session and were then randomized to varenicline or placebo. After 1 week on medication, they completed a cigarette-rating task. Next came a 72-hour abstinence period, with laboratory visits twice per day. The description says participants could receive high-value cash reinforcement contingent on meeting a strict breath carbon-monoxide abstinence criterion. At visits, they rated withdrawal symptoms, mood, and craving. They repeated the cigarette-rating task at the end of abstinence, returned to provide a carbon-monoxide sample 24 hours later, and then texted the laboratory videos of samples for one week. Smoking-relapse timing was to be measured from those samples.

The posted primary-outcome summaries include 3 participants in the varenicline arm and 2 in the placebo arm. The registry lists the primary outcome as the mean Questionnaire on Smoking Urges - Brief Form score during 72 hrs abstinence. Three secondary outcomes are named: satisfaction and reward scales from the Modified Cigarette Evaluation Questionnaire, and latency to smoking relapse. The registry record does not explain why the study was terminated, whether all planned procedures were completed, or how much outcome data were available for each measure.

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

Reasons for not completing this period:

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 - Brief Form, measured over 72 hrs abstinence.

The primary endpoint is the Questionnaire on Smoking Urges - Brief Form score during 72 hrs abstinence. The registry says the score is the average of all items, each rated from 1 (strongly disagree) to 7 (strongly agree). Higher scores indicate higher levels of smoking urge or craving. The posted measure is continuous, and the registry reports a mean and standard deviation for each arm.

As a general measurement concept, a questionnaire score turns reported experiences into a standardized summary that can be described across participants and compared between groups. A craving measure is relevant to this study because the study description includes a monitored abstinence period and repeated assessments of craving, withdrawal symptoms, and mood. The stated endpoint therefore captures a participant-reported experience during the specified abstinence timeframe; it is not itself a direct measure of smoking abstinence or relapse.

The registry reports a mean score of 3.12 with a standard deviation of 2.11 for varenicline, based on 3 participants, and a mean of 4.41 with a standard deviation of 2.72 for placebo, based on 2 participants. Confidence intervals and an inferential comparison for this endpoint are not reported in the registry record. These summaries alone do not establish how precisely the underlying group means or a between-group effect have been estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-masked, parallel study. Randomization is a design method intended to allocate participants to study arms by chance, reducing systematic differences between groups at assignment. Masking is intended to limit the influence of knowledge about assignment on participant experience, study conduct, or outcome assessment. These are general purposes of the design features; the registry record does not report the allocation procedure, concealment details, or how masking was implemented. It also does not report whether any assessment of masking was conducted.

What do the reported means and standard deviations describe?

The primary measure is continuous, and the registry reports a mean and standard deviation in each arm. In general, a mean is the arithmetic average of observed measurements in a group. It summarizes the center of those observations, while the standard deviation describes how dispersed the observations are around their mean. A standard deviation is not a confidence interval and does not show the precision of an estimated treatment effect. Here, the mean and standard deviation are reported for the Questionnaire on Smoking Urges - Brief Form during 72 hrs abstinence: 3.12 and 2.11 for varenicline, and 4.41 and 2.72 for placebo. The corresponding reported group sizes are 3 and 2.

With very small groups, a few observed scores can strongly influence the mean and the estimate of spread. Individual observations are not reported, so the reader cannot assess their distribution, identify influential values, or determine whether a particular distributional assumption is plausible. The registry does not report a confidence interval for either arm mean or for a between-arm contrast. A confidence interval is, in general, a range of estimates produced by a statistical procedure to express uncertainty; its width depends on the data and the method used. No such interval is available in this registry record.

What would an arm comparison add?

A between-arm analysis would estimate the contrast in outcome between participants assigned to varenicline and those assigned to placebo, and could quantify uncertainty in that contrast. The record does not report an estimated contrast or an inferential analysis. It also marks values as missing or not estimable for a two-arm comparison of this continuous endpoint. Consequently, the arm means should be read as separate descriptive summaries, not as a formal estimate of the comparative effect. No recalculated comparison is reported.

In general, a test of a null hypothesis and a confidence interval answer related but different questions. A p-value, when reported, describes how compatible the observed data are with a specified statistical model under a null hypothesis; it does not measure the probability that a treatment works or the size or clinical importance of an effect. A confidence interval communicates an estimated range and its uncertainty under the selected method. Neither a p-value nor an interval is reported for this primary outcome in the registry record. No conclusion about statistical significance can be drawn from the two means and standard deviations alone.

How should the design and outcome timing be understood?

The parallel design means participants were assigned to one study arm, rather than the registry describing each participant receiving both study drugs in sequence. The planned outcome timeframe is 72 hrs abstinence. The study description gives further context about repeated laboratory visits and breath carbon-monoxide assessments, but the posted primary endpoint is the questionnaire score, not a carbon-monoxide measure. General statistical interpretation should keep the outcome definition and timeframe distinct from other measurements collected during the study.

The registry lists smoking-relapse latency as a secondary outcome. Time-to-event methods are used generally when the outcome is the time until an event, while accounting for participants whose event time is not observed during follow-up. The registry record does not report an analysis of relapse latency, the number of events, censoring information, or a statistical model for that outcome. Thus, no time-to-event estimate or conclusion can be described from the posted results.

What role do planning illustrations play?

Planning illustrations based on an observed effect are not the same as observed trial results or observed power. The record describes planning assumptions that include a two-sided significance level of 0.05, equal allocation, and a normal approximation; it also says the effect to detect is a stated fraction of the observed effect. These are assumptions for planning illustrations, not a report of the study's own design justification. The registry does not report the trial's sample-size justification. The planning illustrations should not be read as evidence that the study had adequate power, nor as a substitute for an uncertainty estimate from the observed results.

As a general concept, power is the probability that a specified statistical procedure will detect an effect of a specified size under stated assumptions. It depends on the assumed effect, variability, sample size, significance level, and analysis method. It is not a property that can be inferred from whether a result is statistically significant, and retrospective calculations do not show the probability that a particular observed result is true. The available record does not provide an inferential result for the primary endpoint.

For continuous measurements, another general issue is whether a model's assumptions fit the observed data. For count outcomes, over-dispersion—greater variability than a simple count model assumes—can make standard errors too small if it is ignored. That concept does not establish a problem in this trial, and the registry record does not report a count-outcome model or a dispersion assessment. The principal posted endpoint is continuous, and its analysis method is not reported. It would therefore be speculative to attribute any particular modeling assumption, diagnostic, or correction to the investigators.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Varenicline", "Placebo")
n   <- c(3, 2)
m   <- c(3.12, 4.41)
sp  <- c(2.11, 2.72)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Varenicline  3  3.120  2.110  -2.122  8.362
CARM  Placebo  2  4.410  2.720  -20.028  28.848

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and names three secondary outcomes: the Modified Cigarette Evaluation Questionnaire - Satisfaction Scale, the Modified Cigarette Evaluation Questionnaire - Reward Scale, and latency to smoking relapse. A primary questionnaire outcome is also listed. The registry record does not report which outcomes were tested, whether all planned analyses were conducted, or how multiple outcome comparisons were handled. A multiplicity adjustment or a hierarchy for interpreting outcomes is not reported. In general, testing several outcomes can increase the chance of at least one chance finding if results are interpreted without accounting for the number of comparisons; the record does not establish what approach, if any, was used.

The posted results give arm summaries for the primary endpoint, but do not report an inferential comparison for it. Values are marked as missing or not estimable for a two-arm comparison of this continuous endpoint. The reasons outcome values or a comparison may be unavailable are not reported in the registry record. It does not describe the amount or pattern of missing data, how missing values were handled, or whether any sensitivity analyses were performed. No imputation method is reported.

The analysis population is also not described. The registry does not state whether analyses followed intention-to-treat principles, included only participants who completed study procedures, or used another population definition. It does not report exclusions from the outcome summaries or the reasons for any exclusions. The arm sizes attached to the posted endpoint summaries are 3 for varenicline and 2 for placebo, but these figures alone do not define the analysis population or explain whether all enrolled participants were assessed. The registry record does not report an interim analysis or a statistical analysis plan.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: voluntary psychiatric hospitalization (50.0%).

The registry reports serious adverse events for participants at risk in each arm. In the varenicline arm, 3 participants were listed as at risk and 0 as affected by serious adverse events. In the placebo arm, 2 were listed as at risk and 1 as affected. The registry lists no deaths in either arm. For other, non-serious adverse events, it reports 1 affected participant among 3 at risk in the varenicline arm and 0 affected among 2 at risk in the placebo arm.

The registry lists “voluntary psychiatric hospitalization” as the leading serious adverse event term, with 50.0%. The event-term denominator, the group attribution of that term, and further case details are not reported in the registry record. The figures describe recorded events in a very small study; they are not a reliable basis for estimating how frequently such events would occur in a larger population or for comparing safety between treatments. The registry record does not provide enough detail to assess event timing, severity beyond the serious classification, relatedness to study drug, or the process for determining attribution. These counts describe the posted safety record and do not establish a causal relationship between an intervention and an event.

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

The posted primary-outcome data show mean Questionnaire on Smoking Urges - Brief Form scores of 3.12 for varenicline and 4.41 for placebo during 72 hrs abstinence. The registry also reports standard deviations of 2.11 and 2.72, respectively, with arm sizes of 3 and 2. These values describe the participants represented by the posted summaries. They do not, on their own, establish a treatment effect or the precision of a comparative estimate.

The study's randomized, double-masked design is relevant to how a comparison might be interpreted, but design labels do not replace outcome analysis. The registry record does not report an inferential comparison, a confidence interval, or a p-value for the primary endpoint. It does not report an analysis of the named secondary outcomes. The reason for the terminated status and the degree of completion of planned assessments are also not reported. Those omissions limit what can be concluded from the registry results.

In general, an observed difference between group summaries can arise from a treatment effect, chance variation, or other features of the data and study conduct. With the small reported arm sizes, the summaries are especially limited as estimates of the groups' underlying outcome distributions. A formal uncertainty estimate would help show the range of effects compatible with the observed data under an analysis method, but none is reported for this endpoint.

The questionnaire measures reported smoking urge or craving; it is not a direct measure of abstinence or relapse. The study description includes a monitored abstinence period and follow-up carbon-monoxide sampling, while latency to smoking relapse is listed as a secondary outcome. Results for relapse timing are not reported in the registry record. The primary score therefore cannot be used as a substitute for an unreported relapse analysis.

Overall, the record documents a small terminated study and descriptive primary-outcome and safety summaries. It does not establish whether varenicline or placebo produced a particular effect, nor does it provide a precise comparative estimate. Conclusions should remain limited to the measures and counts that are actually posted.

14. Why This Trial Matters Statistically

This study is statistically informative in part because it illustrates the difference between recording outcomes and estimating a comparative effect. The registry reports arm means and standard deviations for a continuous questionnaire endpoint, but does not report an inferential comparison or uncertainty interval. Readers can see the observed summaries, yet cannot tell from the registry record how precisely a between-arm effect is estimated.

The small reported arm sizes make that distinction especially important. In a small study, a mean can be sensitive to individual observations, and a standard deviation can itself be uncertain. A numerical ordering of group means is not sufficient to establish a stable difference. The study's terminated status and the absence of an explanation for termination add context that cannot be resolved using the available results.

The record also separates outcomes that may sound related but represent different quantities. The primary endpoint measures reported urge or craving during 72 hrs abstinence. The study description also discusses smoking behavior and carbon-monoxide assessments, and the registry names latency to smoking relapse as a secondary outcome. The registry does not report analyses of those secondary measures, so the primary questionnaire summaries should not be interpreted as direct evidence about relapse.

For clinical researchers, the record highlights why outcome definitions, analysis populations, missing-data methods, and multiplicity plans matter alongside arm summaries. Those details are not reported in the registry record. Without them and without an inferential comparison, the available numbers can support a careful description but not a precise statement about comparative effects. The safety counts likewise require cautious reading because the groups are small and event-level context is limited.

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.

The most direct limitation is the small amount of posted primary-outcome data: the registry reports 3 participants in the varenicline summary and 2 in the placebo summary. This makes descriptive estimates vulnerable to the influence of individual observations and limits the precision that can be inferred from the reported means and standard deviations. No confidence intervals are reported.

The study is listed as terminated, but the reason for termination is not reported in the registry record. It is therefore not possible to determine whether termination affected recruitment, follow-up, outcome collection, or the planned analyses. The record does not state whether all participants completed the abstinence procedures or when their primary outcomes were assessed relative to discontinuation.

Although the registry identifies a primary endpoint and three secondary outcomes, it does not report analysis populations, missing-data handling, a statistical analysis plan, or multiplicity procedures. The record does not explain why a two-arm comparison for the continuous endpoint is marked as not estimable. It also does not post an inferential comparison for the primary measure or analyses for the named secondary outcomes.

Further details that would aid interpretation are not reported in the registry record, including participant-level scores, eligibility criteria beyond the described population, allocation procedures, medication regimen details, and the reasons for any unavailable assessments. The safety summary provides limited counts but not detailed event narratives, timing, relatedness, or group attribution for the leading serious event term. These limitations constrain both statistical and clinical interpretation of this record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Targeted Pharmacological and Behavioral Treatments for Smoking in Schizophrenia Study 1 — NCT03507127.
• Registry record last updated 2022-05-17; status last verified 2022-04.
• Results first posted 2022-05-17.
• 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, double-masked, parallel phase 2 study of varenicline versus placebo among smokers with schizophrenia and tobacco dependence. Enrollment is recorded as 5, and study status is terminated. The primary outcome is the mean Questionnaire on Smoking Urges - Brief Form score during 72 hrs abstinence.

The posted primary summaries are a mean of 3.12 and standard deviation of 2.11 for varenicline, based on 3 participants, and a mean of 4.41 and standard deviation of 2.72 for placebo, based on 2 participants. An inferential comparison is not reported in the registry record. Three secondary outcomes are named, but their analyses are not reported. Safety counts include 1 participant affected by a serious adverse event in the placebo arm and none in the varenicline arm; no deaths are listed. The reason for termination, missing-data methods, analysis population, and statistical analysis plan are not reported.