Combination Nicotine Replacement for Alcoholic Smokers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Nicotine Replacement for Alcoholic Smokers (NCT00064844), a randomized phase 4 study. The primary outcome is 6 Month Smoking Abstinence.

2. Clinical Question

This is a treatment comparison within a population described as having alcohol dependence and smoking cigarettes. Its primary outcome is smoking abstinence, not an alcohol outcome. The record identifies cognitive behavior therapy for alcohol and smoking cessation among the interventions, but it does not give enough detail to reconstruct the behavioral treatment schedule or establish how it was delivered across the arms.

3. Trial Design

The registry identifies this as a randomized, quadruple-masked, parallel-group phase 4 trial sponsored by Yale University. Its status is completed. The recorded start is 2002-08, and primary completion is recorded as 2006-07. The registry enrollment is 96. Separately, the brief summary describes a planned sample of 175 people; the record does not explain the difference between that planned figure and the enrollment figure.

The two listed arms are nicotine patch plus active gum and nicotine patch plus placebo gum. Both arm descriptions specify a daily 21-mg patch for 8 weeks, followed by a 14-mg patch for 2 weeks and then a 7-mg patch for 2 weeks, for a total of 12 weeks of patch therapy. The active gum is described as 2 mg uncoated mint nicotine gum; the placebo arm is described as receiving placebo gum for ad libitum use. The placebo-gum description is truncated in the registry record, and further administration details are not reported in the registry record.

The brief summary describes a 6-month outpatient alcohol and tobacco treatment program and follow-up assessments for 1-year from the beginning of treatment. The primary endpoint, however, is framed at 6 months after the smoking quit date. The registry does not report how the quit date was established, the exact timing of assessments, or whether all planned assessments were completed. Although quadruple masking is recorded, the identities of the masked groups 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 6 Month Smoking Abstinence, measured over 6 months after smoking quit date.

The primary endpoint is titled 6 Month Smoking Abstinence. It measures the percentage of participants with prolonged smoking abstinence verified by carbon monoxide, assessed at 6 months after the smoking quit date. The posted value is 20.0 for nicotine patch plus active gum and 12.0 for nicotine patch plus placebo gum.

Abstinence is a clinically interpretable outcome because it describes whether participants met a defined smoking-cessation state, rather than reporting a change in a laboratory measure alone. Carbon monoxide verification adds an objective check to the abstinence assessment. The word prolonged indicates that the endpoint concerns sustained abstinence as defined by the study, but the exact operational definition, including any allowed lapses or assessment window, is not reported in the registry record.

The outcome is expressed as a percentage, but the registry record does not provide the event counts underlying those values or an uncertainty interval for either arm. It also does not describe how missing or unverified abstinence assessments were handled. Those details matter when interpreting a percentage: the estimate depends on the outcome definition, the participants included in its denominator, and the approach to missing observations. Without those details, the posted values describe the registry results but do not establish their precision or the robustness of the comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint estimate?

For a binary outcome such as abstinent or not abstinent, a percentage describes the share of participants who meet the outcome definition in an arm. In this trial, the endpoint is prolonged smoking abstinence with carbon monoxide verification at 6 months after the quit date. A percentage is easy to interpret, but interpretation requires knowing which participants form its denominator and how unavailable assessments were treated. The registry does not report those details, nor does it provide the underlying event counts.

The two posted arm values are descriptive estimates. A comparison of arms would usually quantify the contrast between their outcome rates and its uncertainty. The registry record states that values are missing or not estimable for a two-arm comparison of this count outcome. It therefore does not support a recalculated inferential comparison based on the posted summaries. The arm values should not be turned into a claim of statistical significance or a precise treatment effect.

Why does uncertainty matter?

A confidence interval is a range of values compatible with the observed data and a specified statistical procedure. In general, a narrow interval indicates greater precision than a wide interval, while an interval spanning effects in different directions may leave the comparison uncertain. These general principles do not supply an interval for this trial: none is reported in the registry record. The group percentages alone cannot show how much random variation is plausible.

A test of a treatment contrast also depends on more than the arm-level percentages. It requires the outcome counts or suitable model results, the analysis population, and a prespecified statistical approach. The record does not report a test statistic or p-value for the primary two-arm contrast. It is therefore important to distinguish an apparent numerical separation between arm summaries from an inferential result about that separation.

How should the design be read?

In a randomized trial, assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured characteristics. A parallel-group design means the listed arms are separate groups rather than sequential treatment periods for each participant. Masking is intended to limit the influence of treatment knowledge on behavior or assessment, but the record does not state which people were masked, how masking was maintained, or whether it was assessed.

Randomization does not guarantee that every observed characteristic is balanced, and it does not address losses to follow-up or missing outcome data by itself. The registry record does not report allocation concealment, baseline characteristics, adherence, or the flow of participants from randomization to analysis. These omissions limit assessment of how closely the reported outcome estimates reflect the randomized comparison.

What do the planning assumptions mean?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such illustrations answer a hypothetical design question: how many participants per arm might be needed under stated assumptions to detect a specified fraction of an observed effect. They are planning aids, not evidence that the completed trial had a particular probability of detecting an effect. They are not observed power.

The illustrations are not the trial's own design justification. The registry does not report the original sample-size calculation, the target effect used in planning, or a justification for the recorded enrollment. The brief summary's planned sample and the recorded enrollment are not reconciled. Further, planning based on an observed effect can depend on the size of that estimate, which may be imprecise. No interpretation of the planning illustrations can replace a confidence interval or an appropriate analysis of the trial results.

Why can counts require special care?

For count outcomes, statistical methods may need to account for the way events vary across participants. In general, over-dispersion occurs when the observed variability in counts is greater than a model assumes; ignoring it can make uncertainty look too small. That concept is general and is not evidence that over-dispersion occurred in this trial. The primary endpoint is reported as a percentage of participants abstinent, and the registry provides no count model, dispersion estimate, or inferential analysis for the arm comparison.

In short, the posted outcome values describe the two arms, but the record does not provide the elements needed to reconstruct an uncertainty estimate or formal comparison. Interpretation should stay at the descriptive level unless a fuller statistical report supplies the analysis population, outcome counts, handling of missing data, and inferential results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, 1 analysis, and 0 posted secondary outcomes. Those record entries do not establish how many hypotheses were planned, which outcome was designated primary in the original protocol, or whether any adjustment for multiple testing was intended. A multiplicity plan is not reported in the registry record. Without it, the possibility of selective emphasis across outcomes or analyses cannot be assessed from the registry entries alone.

The record does not report the analysis population for the primary endpoint. It does not say whether the outcome analysis followed randomized assignment regardless of treatment adherence, included only participants with observed outcome data, or used another approach. It also does not describe the number or reasons for missing assessments, imputation, sensitivity analyses, or rules for classifying participants without verification. These details are important for an abstinence endpoint because the resulting percentage can depend on how unavailable outcomes are handled.

The brief summary describes follow-up assessments for 1-year from the beginning of treatment, whereas the posted primary endpoint is assessed at 6 months after the smoking quit date. The relationship between the follow-up schedule and the endpoint assessment is not reported in the registry record. A protocol, statistical analysis plan, and details of interim analyses are also not reported in the registry record, so their existence or contents should not be inferred.

The count of analyses in the registry is not enough to establish that the reported analysis was the only analysis conducted. Nor does the absence of posted secondary results establish that no secondary outcomes were collected. The available record supports only the narrow statement that no secondary outcomes are posted there.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record reports serious adverse events affecting 0 participants among 45 at risk in the nicotine patch plus active gum group, and 0 among 51 at risk in the nicotine patch plus placebo gum group. These figures describe the registry's reported serious adverse-event counts for the listed at-risk groups. They do not establish that no other safety concerns occurred, and the record does not provide event descriptions for serious adverse events.

For other adverse events, the record reports 1 affected participant among 45 at risk in the active-gum group and 7 among 51 at risk in the placebo-gum group. The specific event terms are not reported in the registry record. The adverse-event denominators differ from the group sizes listed for the primary endpoint, and the reason for that difference is not reported. These counts should not be treated as rates for the primary outcome groups or compared without accounting for the differing denominators and reporting context.

Deaths are not reported in the registry record. The absence of listed serious adverse-event terms does not mean that all adverse events were absent; the registry reports other adverse-event counts. Safety counts are descriptive and, without fuller definitions, follow-up information, and an analysis plan, do not establish a causal safety difference between the arms.

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

The posted results establish that the registry records arm-specific abstinence values of 20.0 for nicotine patch plus active gum and 12.0 for nicotine patch plus placebo gum for prolonged, carbon monoxide-verified smoking abstinence at 6 months after the quit date. They also establish that the registry marks values as missing or not estimable for a two-arm comparison of this count outcome. This is a descriptive result, not a reported inferential comparison.

The values do not show the precision of either estimate. No confidence intervals, event counts underlying the percentages, or p-value for the arm contrast are reported. The values alone cannot determine whether the observed separation is consistent with chance variation, nor can they establish the size or reliability of an underlying treatment effect.

The registry's design information describes a randomized, quadruple-masked, parallel-group trial. These features are relevant to interpreting evidence, but the record does not provide enough detail to evaluate implementation, masking roles, participant flow, treatment adherence, or missing outcome handling. The mismatch between the planned sample described in the brief summary and the recorded enrollment is not explained. No sample-size justification is reported in the registry record.

The results also do not answer questions about smoking outcomes beyond the stated endpoint, alcohol outcomes, long-term abstinence beyond the assessment described, or the comparative safety profile. Although the brief summary mentions follow-up assessments for 1-year from treatment start, the registry excerpt does not give further outcome results or clarify their relation to the primary endpoint. These limits mean the posted entries should be read narrowly: they describe the recorded outcome values and safety counts, while leaving important questions about uncertainty and analysis unresolved.

Nothing in these registry entries alone establishes that one regimen is superior, equivalent, or ineffective. A fuller trial report could provide prespecified methods, participant-flow information, outcome definitions, missing-data handling, and inferential results that allow a more complete assessment.

13. Why This Trial Matters Statistically

This trial raises several statistical issues that recur in clinical research. First, a percentage is an accessible way to present a binary outcome, but it is incomplete without a clear denominator and an account of missing assessments. The record lists group sizes for the primary outcome, but does not explain the analysis population or provide the underlying abstinence counts. That makes it difficult to reconstruct uncertainty independently.

Second, a randomized design and a descriptive difference are not the same as an inferential conclusion. Randomization supports a fair comparison when implemented and analyzed appropriately, but the registry does not report an estimable two-arm analysis for the primary count outcome. Reporting group values without an uncertainty estimate can invite overinterpretation. The distinction between descriptive results and a formal treatment contrast is central to sound statistical reading.

Third, the record illustrates why consistency across planning, enrollment, outcome reporting, and safety reporting matters. The brief summary describes a planned sample of 175, while the registry lists enrollment of 96. The primary outcome group sizes and safety denominators also differ. These entries may reflect different reporting populations or record history, but the reasons are not reported. Readers cannot resolve those differences from the registry information alone.

Finally, planning illustrations based on an observed effect should not be mistaken for observed power or for the trial's original sample-size justification. A planning calculation is conditional on assumptions; an observed result remains subject to uncertainty. Keeping these concepts distinct helps prevent a descriptive result from being presented as more conclusive than the record supports.

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.

Several trial-specific limitations of the registry record constrain interpretation. The planned sample described in the brief summary is 175, while recorded enrollment is 96, and no explanation is given. The group sizes listed with the primary endpoint are 39 and 40, whereas the safety groups list 45 and 51 at risk. The record does not explain how these populations relate or why the denominators differ.

The primary outcome is clearly named and timed, but its full operational definition is not reported. The record does not state how prolonged abstinence was defined in detail, how carbon monoxide verification was applied, or how missing or unverified assessments were classified. The posted percentages are not accompanied by their underlying outcome counts or uncertainty intervals, and a two-arm comparison is marked missing or not estimable.

The record also lacks participant-flow details, adherence information, baseline characteristics, an original sample-size justification, and an analysis-population definition. Masking is described as quadruple, but the masked roles and the practical implementation are not reported. Although a behavioral intervention is listed, details of its delivery and consistency between groups are not reported in the registry record. The placebo-gum arm description is incomplete. Finally, the record provides no posted secondary outcome results and does not explain how the stated follow-up period relates to the primary endpoint timing.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combination Nicotine Replacement for Alcoholic Smokers — NCT00064844.
• Registry record last updated 2021-08-13; status last verified 2021-08.
• Results first posted 2013-04-16.
• 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

This completed phase 4 trial is recorded as randomized, quadruple-masked, and parallel-group, with Yale University as sponsor. It compares nicotine patch plus active gum with nicotine patch plus placebo gum among smokers described as having alcohol dependence. The primary outcome is prolonged, carbon monoxide-verified smoking abstinence at 6 months after the smoking quit date.

The registry lists abstinence values of 20.0 for the active-gum arm and 12.0 for the placebo-gum arm, but states that values are missing or not estimable for a two-arm comparison. The record lists enrollment of 96, while the brief summary describes a planned sample of 175. Serious adverse events affected 0 participants in each reported safety group; other adverse-event counts are 1 and 7. The record does not report deaths, a formal comparison estimate, or secondary outcome results.