Smoking-Cessation and Stimulant Treatment (S-CAST): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Smoking-Cessation and Stimulant Treatment (S-CAST) (NCT01077024), a randomized phase 3 study. The primary outcome is Stimulant-free Weeks Assessed by Self-report and Twice-weekly Urine Drug Screens.

2. Clinical Question

3. Trial Design

S-CAST was a Phase 3, randomized, parallel-group trial with no masking reported. The registry record lists enrollment of 538 and describes two treatment strategies: smoking-cessation treatment added to substance-treatment as usual, and substance-treatment as usual alone. The study was sponsored by the University of Cincinnati and is listed as completed. Its start is recorded as 2010-02, with primary completion in 2012-08.

The target clinical setting was outpatient treatment for stimulant dependence among smokers. The listed conditions were cocaine dependence, methamphetamine dependence, and nicotine dependence. The intervention description names smoking-cessation treatment, while the comparator description characterizes usual care as outpatient stimulant-dependence treatment as typically provided by the participating site. Specific intervention components and details of the usual-care programs are not reported in the registry record.

Randomization supports a planned comparison between the assigned strategies, but the record does not report the sequence-generation method, allocation concealment, stratification factors, or whether assignment was implemented as planned. No masking was used, so participants and treatment providers were not blinded according to the registry entry. Whether outcome assessors were masked is not reported in the registry record.

The primary outcome combined urine drug screen results and self-reported Timeline Follow-Back information to classify weeks without cocaine, methamphetamine, or amphetamine use. Secondary outcomes covered smoking abstinence and stimulant-free results at follow-up visits. The record does not report the sample-size justification, a prespecified statistical analysis plan, or a primary analysis population. Those omissions limit how fully the design and inferential approach can be evaluated from the registry record alone.

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.

Population: The baseline analysis was performed on the Intent-to-Treat population, which was the population of randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Stimulant-free Weeks Assessed by Self-report and Twice-weekly Urine Drug Screens, measured over Week 16.

The primary endpoint was the percentage of weeks that were stimulant-free at Week 16. A stimulant-free week meant no cocaine, methamphetamine, or amphetamine use, based on a combination of urine drug screens and self-reported Timeline Follow-Back information. The endpoint therefore brings together a biological measure and participant-reported information rather than relying on either source alone.

The registry describes the endpoint as a group-level percentage of weeks in each study arm. It is not a percentage of participants who were abstinent throughout the whole study, nor does it represent a single urine test result. It summarizes how often weeks met the stimulant-free definition within each group over the assessed period. Such a measure can capture patterns of use over time, while still depending on the completeness and classification of both assessment sources.

The posted group values are 77.7% for smoking-cessation treatment plus usual care and 78.0% for usual care alone. The registry record does not report a formal two-arm comparison for this primary endpoint. It also displays bounds of 0.694 to 1.32 for both arm rows, but does not explain their interpretation; they cannot be read as percentage-point uncertainty bounds without clarification. Consequently, the group percentages can be described, but the primary result’s inferential precision and statistical significance are not established by the posted primary results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation depends on distinguishing endpoint summaries from treatment comparisons. An arm-level percentage describes the outcome within that group. A between-arm effect estimate instead describes a contrast, with a stated direction and uncertainty. The registry record reports the primary group percentages but does not report a primary contrast or an analysis for that endpoint. That means the primary group values can be described directly, but they do not by themselves quantify the uncertainty around the treatment difference.

What does a confidence interval express?

As a general statistical concept, a confidence interval gives a range of values compatible with the observed data under the assumptions of the method. It is not a range containing a specified probability that the true effect lies inside it. For a risk difference, zero represents no difference between groups. An interval that crosses zero therefore includes values corresponding to no difference as well as values in both directions. Intervals should be interpreted alongside the effect estimate, endpoint definition, and analysis method.

For the posted secondary comparisons, the risk difference is oriented as the usual-care group minus the combined-treatment group. A negative estimate therefore corresponds to a lower observed proportion in the usual-care group for that outcome. This direction matters: a negative sign does not, by itself, indicate whether an outcome is desirable or undesirable. The estimate and interval describe the contrast as coded, while clinical interpretation depends on what the endpoint measures.

What does an unadjusted p-value tell the reader?

As a general concept, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model. It is not the probability that the observed difference arose by chance, and it is not a measure of effect size. The unadjusted p-values associated with the secondary comparisons do not account for the fact that several outcomes are listed. The registry record does not state whether those comparisons were prespecified, how multiplicity was handled, or which outcome was intended to carry confirmatory weight beyond the designated primary endpoint.

The values for the secondary comparisons are simple unadjusted calculations from the posted summaries, rather than sponsor-reported analyses. The registry record lists no reported analyses for those outcomes. They should therefore be treated as descriptive analytical aids, not as a replacement for a trial analysis that specifies covariates, population, missing-data methods, and multiplicity procedures. The discrepancy flag is false, so no disagreement with a sponsor analysis is identified; nevertheless, the absence of a sponsor-reported analysis remains important.

Why are planning illustrations not observed power?

Planning illustrations use an assumed effect and statistical assumptions to show what participant counts might be needed in a future study. The record states that these illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and a stated fraction of the observed effect. For the secondary outcomes with planning rows, the displayed scenarios range from using 100% of the observed effect to using 50% of it, with 75% also shown. They are not the enrollment target reported for S-CAST, and they do not show the probability that this completed trial detected an effect. The record explicitly says the planning calculations are not the trial’s own design.

Planning values can be sensitive to the observed effect used as their starting point. As a general statistical matter, an effect estimated in a study can be imprecise, and planning for a smaller assumed effect requires a larger study under otherwise fixed assumptions. The posted planning rows illustrate that sensitivity; they do not establish that the original trial was adequately or inadequately powered. The sample-size justification for S-CAST is not reported in the registry record.

How should the primary endpoint bounds be handled?

The primary group summaries are reported as percentages, while the same bounds, 0.694 to 1.32, appear for both arm rows. The record does not identify what those bounds represent or how they relate to the endpoint’s percentage unit. It would not be appropriate to relabel them as confidence intervals for the group percentages or for a treatment contrast. The endpoint description also says the outcome is a group-level percentage of weeks, while the posted analysis metadata identifies a count-type outcome and notes that a two-arm comparison is not estimable. Without a stated method or comparison, no inferential meaning should be attached to the bounds.

Combining urine drug screens and self-reported Timeline Follow-Back information is part of the endpoint definition, not itself a statistical adjustment. The registry does not say how conflicting results were resolved, how missing assessments were classified, or how repeated observations contributed to the group-level summary. Those details can affect interpretation and reproducibility. As a general matter, repeated measures across time may require methods that account for their dependence; the registry record does not report whether or how that dependence was addressed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and six secondary outcomes. It does not report how the family of outcomes was handled statistically, whether any secondary outcomes were designated as confirmatory, or whether a multiplicity adjustment was planned. Without that information, the unadjusted p-values for secondary comparisons should not be treated as if each were the sole prespecified test. As a general statistical issue, evaluating several outcomes can increase the chance of at least one apparently notable result even when there is no underlying effect.

Missing-data methods are not reported in the registry record. The record gives arm-specific counts for some outcomes that are lower than the enrollment figures, but does not explain the reasons for those differences, whether follow-up data were missing, or how missing outcomes were handled. It does not state whether analyses used complete cases, imputation, a particular assumption about missingness, or another approach. No such method should be inferred from the posted counts alone.

The primary endpoint combines urine drug screens with self-reported Timeline Follow-Back information, but the registry record does not describe how unavailable tests or reports were classified, how conflicting sources were resolved, or how the weekly data were aggregated when information was incomplete. These details matter because different rules can change the percentage of weeks counted as stimulant-free.

The analysis populations are also not reported in the registry record. It is not stated whether results were analyzed according to randomized assignment, treatment received, or another population definition. The record does not describe participant flow after randomization or provide reasons for any exclusions. As a result, the relationship between allocation, follow-up, and the posted outcome denominators cannot be fully assessed.

These omissions do not establish that the analyses were inappropriate; they limit what can be concluded from the registry record. A complete assessment would need the prespecified analysis plan, missing-data procedures, analysis-population definitions, and documentation of how all listed outcomes were handled.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (0.7%), suicidal ideation (0.7%), angina pectoris (0.7%), vision blurred (0.4%), chest pain (0.4%).

The registry lists serious adverse event counts of 14 in the smoking-cessation-plus-usual-care group and 9 in the usual-care group. It also lists other adverse event counts of 181 and 89, respectively. These are posted counts, not rates adjusted for exposure time, and the registry record does not define the event categories or explain how events were collected and attributed. The counts alone cannot establish whether the groups differed in safety.

The listed serious adverse event terms include Depression, Suicidal ideation, and Angina Pectoris at 0.7% each, and Vision blurred, Chest pain, and Death at 0.4% each. These percentages are presented as top serious terms, but the registry record does not specify the denominator or provide a group-specific breakdown for those terms. The death count is listed as null for both arms, so the 0.4% term should not be interpreted as a reported arm-specific death count.

Comparisons of adverse event counts require context about definitions, exposure, follow-up, severity, and completeness of reporting. Those details are not reported in the registry record. These figures should therefore be read as the adverse-event entries recorded, not as a complete comparative safety analysis.

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

The posted primary result describes the proportion of weeks classified as stimulant-free in each group at Week 16. The two reported values are 77.7% for the combined-treatment group and 78.0% for usual care alone. They are group summaries, not estimates of the effect of adding smoking-cessation treatment. The registry record does not report a formal primary comparison, so it does not establish the size or precision of a primary treatment effect.

The secondary results provide additional descriptive information about smoking abstinence and stimulant-free outcomes at follow-up. Some unadjusted comparisons show clear separation in the posted smoking outcomes, while the later stimulant-free comparison has an interval that includes zero and an unadjusted p-value of 0.182. Because these are secondary, unadjusted calculations and the multiplicity approach is not reported, they should not be interpreted as a complete confirmatory analysis.

The findings do not establish that smoking-cessation treatment caused a change in stimulant use, nor do the primary summaries establish equivalence between the treatment strategies. A lack of a reported primary test is not evidence that the strategies are identical. Likewise, a secondary p-value does not state the probability that an effect is real, and a statistically notable result does not, on its own, establish clinical importance.

The results are specific to the outpatient context described in the record and the enrolled population of smokers receiving treatment for cocaine or methamphetamine dependence. The registry record does not provide enough detail about eligibility, treatment delivery, missing data, or analysis populations to judge how readily the results apply to other settings. These qualifications concern the scope and interpretation of the evidence, not an individual treatment decision.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is a group-level summary of repeated weeks, assembled from both urine drug screens and self-reported information. That definition raises questions about how repeated measurements, missing assessments, and disagreements between data sources were handled. The registry record gives the endpoint concept but does not report those operational or analytical details, making it difficult to reproduce or fully evaluate the primary result.

The record also illustrates why a close pair of group percentages is not, by itself, a complete comparison. The primary values are 77.7% and 78.0%, but no formal contrast or interpretable uncertainty interval is reported. A statistical assessment needs both an effect estimate and a description of its uncertainty, supported by a clear analysis method. Without those elements, readers should not infer either a meaningful difference or equivalence from the group values alone.

Several secondary endpoints create a separate issue: the posted unadjusted comparisons do not come with a reported multiplicity strategy or analysis plan. As a general statistical principle, the more outcomes examined, the more important it is to distinguish confirmatory findings from exploratory patterns. The record’s planning illustrations also show why sample-size calculations based on observed effects are scenario tools rather than evidence of observed power or proof that the trial’s design was adequate.

Finally, randomized allocation and an open-label parallel design are not enough to characterize the full analysis. Allocation procedures, outcome-assessment masking, analysis populations, missing-data handling, and sponsor-reported statistical analyses are not reported. These reporting gaps matter because they govern how confidently the descriptive results can be connected to the intended treatment comparison.

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 main trial-specific limitation in the posted results is the absence of a formal comparison for the primary endpoint. The registry gives arm-level percentages for stimulant-free weeks at Week 16, but does not report a primary effect estimate, confidence interval with an interpretable definition, or p-value. The identical bounds attached to both arm rows are not explained, so they cannot be used to quantify uncertainty for the primary comparison.

The endpoint relies on both urine drug screens and self-reported Timeline Follow-Back information. The record does not report how those sources were reconciled, how missing weeks were handled, or whether a positive result from either source was sufficient to classify a week as not stimulant-free. The group-level aggregation method is also not described. These omissions limit reproducibility and assessment of potential measurement effects.

The randomized, unmasked, parallel design is identified, but important implementation details are absent. Sequence generation, allocation concealment, treatment adherence, intervention duration and delivery, site variation, and masking of outcome assessors are not reported in the registry record. The record also does not define the analysis population or explain the difference between enrollment and outcome-specific denominators.

Several secondary outcomes are listed, but the record does not state a multiplicity plan or provide sponsor-reported analyses. The unadjusted comparisons cannot answer every question about confounding, missingness, or longitudinal patterns. The sample-size justification and original analysis plan are not reported. Finally, the serious and other adverse event counts lack details on definitions, exposure, attribution, and group-specific term frequencies. These limits concern what can be evaluated from the registry record; they do not, by themselves, show that trial conduct or analysis was deficient.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Smoking-Cessation and Stimulant Treatment (S-CAST) — NCT01077024.
• Registry record last updated 2021-09-29; status last verified 2021-09.
• Results first posted 2014-08-20.
• 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

S-CAST was a completed, Phase 3, randomized, open-label, parallel-group trial sponsored by the University of Cincinnati. Enrollment was 538. It compared smoking-cessation treatment added to outpatient substance-treatment as usual with substance-treatment as usual alone among smokers receiving treatment for cocaine or methamphetamine dependence. The registry lists nicotine dependence as a condition and records the study start as 2010-02 and primary completion as 2012-08.

The primary endpoint was the percentage of weeks without cocaine, methamphetamine, or amphetamine use at Week 16, based on urine drug screens and self-reported Timeline Follow-Back information. The posted group values were 77.7% and 78.0%, respectively, but a formal primary between-arm analysis is not reported in the registry record. Secondary outcomes addressed smoking abstinence and stimulant-free results at follow-up. The record does not report the statistical analysis plan, multiplicity handling, missing-data methods, or analysis populations, limiting the inferential conclusions that can be drawn from the posted results.