Effect of Varenicline on Fixed-Dose Alcohol Administration in Participants With Alcohol Use Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Varenicline on Fixed-Dose Alcohol Administration in Participants With Alcohol Use Disorders (NCT01000987), a randomized phase 2 study. The primary outcome is Cognitive Function as Measured by Omissions on the CPT.

2. Clinical Question

The central question is whether cognitive performance, measured by omissions on the Continuous Performance Task (CPT), differs in participants with alcohol use disorders receiving varenicline or placebo during a laboratory alcohol-administration task. The record describes a high alcohol dose of 0.08 g/dL and placebo alcohol, with attention to the ascending and descending limb of the blood alcohol curve.

The CPT task assesses attention and response inhibition. Participants see “go” and “stop” targets and are instructed to respond to go targets while avoiding a response to stop targets. An omission is a target-present trial on which the participant does not respond. The planned clinical question is therefore about performance on a specific cognitive task under experimental conditions, not about alcohol use or broader functioning outside the task. The available registry information does not establish which dose, beverage condition, or time point produced a difference, nor how large any such difference might be.

3. Trial Design

The registry describes a completed, randomized, triple-masked, parallel-model phase 2 study sponsored by Yale University. Enrollment is listed as 44. The study started in 2009-10, and primary completion is listed as 2016-11. The record names varenicline and placebo as drug interventions, with descriptions of varenicline 1 mg/day or 2 mg/day and a placebo group.

The experimental task involved consumption of a high-dose alcohol beverage, described as 0.08 g/dL, or a placebo-alcohol beverage. The stated purpose was to examine cognition across the ascending and descending limb of the blood alcohol curve. The primary outcome timeframe specifies that testing followed 3 weeks of medication and that the CPT was performed at 60 minutes following alcohol or placebo beverage consumption. The record does not provide further detail about the precise sequence of task conditions or how repeated observations, if any, were assigned to analysis.

Randomization indicates that assignment was intended to use a chance-based process, but the allocation procedure and allocation ratio are not reported in the registry record. Triple masking is the recorded masking designation; which participants, investigators, assessors, or other personnel were masked is not reported. The parallel model indicates that the study is classified as a parallel-group design, but the record does not explain the full relationship between medication groups and beverage conditions.

The record lists 44 enrolled participants and describes three medication groups in its safety information. It does not explain the relationship between enrollment and the numbers listed as at risk in those groups. Detailed participant flow, withdrawals, adherence, baseline characteristics, and the number contributing to each cognitive outcome are not reported in the registry record. The status is completed, but completion alone does not establish that the planned outcome was fully analyzed or that numerical results were posted.

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 Cognitive Function as Measured by Omissions on the CPT, measured over Following 3 weeks of medication. The CPT task was performed at 60 minutes following alcohol or placebo beverage consumption..

The primary endpoint is cognitive function measured as the number of omissions on the Continuous Performance Task. An omission occurs when a target is present but the participant does not respond. The task presents “go” and “stop” targets: participants are asked to press the space bar for go targets and to withhold a response for stop targets. The registry describes the CPT as assessing attention and response inhibition.

The measure is a count, summarized in the record as a mean with standard error. Higher omission rates indicate a greater level of inattention. The stated range is 0-324. In this experimental context, the count offers a way to quantify missed target responses during a standardized task after medication and alcohol or placebo-alcohol beverage consumption.

Using this endpoint focuses the question on observable task performance rather than a general impression of cognition. It does not, by itself, measure every aspect of attention, response inhibition, or daily functioning. The recorded timeframe places the task after 3 weeks of medication and at 60 minutes following the beverage. However, no numerical means, standard errors, confidence intervals, or tests for the primary endpoint are reported in the registry record. The registry also notes that the primary outcome has several categories or time points and was not reduced to one comparison, so the precise contrast represented by a single summary estimate is not available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details available for the primary outcome are limited. The registry calls the outcome continuous and specifies a mean as the parameter and standard error as the dispersion measure. It does not report the means, standard errors, comparisons, or model results. The methods below explain how such quantities are generally interpreted; they do not describe an analysis that can be verified from this record.

What does a mean represent?

For a continuous outcome, a mean is the arithmetic average of participant measurements within a defined group or condition. Here the measurement is the number of CPT omissions. A mean can provide a compact description of typical task performance, but it does not show the full distribution. Participants may have similar counts or widely varying counts while sharing the same mean. The registry gives the endpoint’s range as 0-324 and states that higher omission rates indicate greater inattention.

To interpret a mean contrast, readers need to know which groups or conditions are being compared, which participants contributed, and whether measurements were taken at one time or across multiple conditions. The record describes different medication doses, placebo medication, alcohol and placebo-alcohol beverages, and the ascending and descending limb of the blood alcohol curve. It does not report a single reduced comparison or explain the exact structure of the primary analysis. Thus, a mean for one condition cannot be assumed to answer every part of the stated study question.

How should standard error be read?

In general, the standard error characterizes the sampling precision of an estimated mean. It is not the same as the standard deviation, which describes variation among individual observations. A smaller standard error generally corresponds to a more precise estimate under the assumptions of the analysis, while a larger standard error indicates greater uncertainty in the estimated mean. No standard errors are posted for the primary outcome, so the precision of any group mean cannot be evaluated.

A confidence interval combines an estimate with a range of values compatible with the data and the interval’s statistical procedure. In general, a narrow interval indicates greater precision than a wide interval, but interpretation depends on the estimand and analysis assumptions. No confidence intervals for CPT omissions are reported in the registry record. There is therefore no interval-based assessment of the size or precision of a medication or beverage contrast.

What would a comparison require?

A treatment comparison would ordinarily specify the outcome contrast of interest, such as a difference in mean omissions between defined groups or conditions. It would also specify the analysis population, handling of repeated task conditions, covariates if any, and the method for estimating uncertainty. The record identifies randomization and a parallel model but does not provide these analysis details. It reports zero posted analyses, and the primary outcome’s several categories or time points are not reduced to one comparison.

For a continuous measure, methods may rely on assumptions about the outcome distribution or use approaches suited to the observed data structure. General concerns include skewness, bounded counts, and dependence among repeated measurements. These are methodological considerations, not claims about the actual distribution or methods used in this trial; those details are not reported in the registry record. The record does not identify a statistical model, adjustment strategy, hypothesis test, or procedure for repeated observations.

How do the planning illustrations relate to the trial?

The planning assumptions described for illustrative sample-size calculations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the convention is participants per arm; time-to-event calculations use a total number of events. These are planning illustrations based on an observed effect, not the trial’s own design justification, and they are not observed power. No numerical planning quantities or sample-size justification are reported in the registry record.

In general, a planning calculation depends on the assumed effect, variability, significance level, power target, and allocation. Changing those assumptions changes the planning result. Such calculations do not establish what effect the trial actually observed, and an illustration based on an observed effect should not be mistaken for the protocol’s original rationale. The record does not report the original sample-size assumptions, a target enrollment justification, or whether any planned calculation informed the trial.

Overall, the registry provides enough information to identify the endpoint’s basic meaning and the intended experimental setting, but not to reconstruct or evaluate the statistical analysis. Numerical outcome estimates, uncertainty measures, and analysis methods are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described as having several categories or time points, and the registry indicates that it was not reduced to one comparison. The exact set of planned or performed comparisons is not reported in the registry record. This leaves unclear how the study intended to distinguish the primary contrast from other possible contrasts across medication doses, beverage conditions, or task time points.

In general, testing several outcomes or contrasts can increase the chance of observing at least one apparently unusual result when all null hypotheses are true. Statistical plans may address this by defining a primary comparison in advance or by adjusting inference across multiple comparisons. The registry record does not report whether any multiplicity strategy was planned or used. Since no primary-outcome analyses are posted, there are no reported adjusted or unadjusted results to interpret.

Missing-data handling and analysis populations are also not reported in the registry record. The record does not state how missing CPT measurements, withdrawals, or incomplete task sessions were handled, nor does it identify an intention-to-treat, per-protocol, or other analysis population. Participant flow and the number contributing to each outcome are not given.

These omissions matter because the interpretation of a mean depends on who was included and which measurements were available. If observations were missing, the method used to handle them could affect estimates and their uncertainty. Without those details, the completeness and representativeness of any potential endpoint analysis cannot be assessed. The registry’s completed status does not resolve these unanswered questions.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events separately for 1 mg/Day Varenicline, 2 mg/Day Varenicline, and Placebo. Each group is recorded as having 20 participants at risk for serious events, with 0 participants affected by serious adverse events in each group. Deaths are recorded as 0 in each group, and no serious adverse event terms are listed.

These figures describe the serious-event counts entered in the registry. They do not show that no adverse events of any kind occurred: the same safety information lists other, non-serious adverse events affecting 4 participants in the 1 mg/Day Varenicline group, 5 in the 2 mg/Day Varenicline group, and 7 in the Placebo group. These other-event counts are distinct from the serious-event counts.

The record lists enrollment as 44, while the safety information lists 20 at risk in each of three groups. It does not explain the relationship between those figures, so the safety denominators should be read as recorded rather than reconciled with enrollment. Zero serious events in the listed groups is a descriptive finding for the registry entry; it does not by itself establish comparative safety or rule out events not captured in the posted record.

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

The registry record documents a randomized, triple-masked phase 2 study of varenicline and cognitive task performance after alcohol or placebo-alcohol beverage consumption. It defines the primary outcome as the number of omissions on the CPT and explains how the task measures missed responses to targets. It also identifies the medication doses, the testing timeframe, and the laboratory context.

What the record does not establish is the result of the primary cognitive comparison. No means, standard errors, confidence intervals, p-values, or analysis results are posted. The record notes that the outcome has several categories or time points and was not reduced to one comparison. Without results and a clear contrast, the size, direction, and precision of any difference in omissions cannot be determined.

The endpoint should also be understood narrowly. CPT omissions provide a task-based measure associated in the record with inattention. They are not a complete measure of cognition, behavior outside the laboratory, or participants’ broader functioning. The experimental conditions described do not, on their own, establish what would occur in other settings.

The safety figures report no serious adverse events or deaths in the listed groups, while also listing non-serious adverse events. Those counts are descriptive and do not answer the cognitive question. Likewise, planning illustrations, where used, concern assumptions for sample-size planning and are not evidence of an observed treatment effect or of observed power.

The sound conclusion is limited: the study’s objective and endpoint are identifiable, but the posted registry information does not permit a quantitative conclusion about cognitive outcomes. It would be inappropriate to treat completion status, design labels, or safety counts as substitutes for the missing primary-outcome analysis.

13. Why This Trial Matters Statistically

This trial raises a useful statistical problem: the outcome is measured in a controlled task, while the study question involves multiple experimental dimensions. Medication assignment, beverage condition, task timing, and the ascending or descending limb of the blood alcohol curve all shape what a comparison would mean. A clearly defined estimand—the precise contrast the analysis aims to estimate—is essential when several conditions or time points are involved.

The record also illustrates why an endpoint definition and a result are different kinds of information. The CPT omission count is described in enough detail to understand what was measured and how higher counts are interpreted. But without group estimates, uncertainty measures, and the comparison structure, readers cannot evaluate the magnitude or precision of an outcome difference. A well-defined measure alone does not answer the statistical question.

Another important point is the distinction between a planning illustration and a trial’s original design rationale. Sample-size calculations depend on assumptions, and an illustration based on an observed effect is not the same as a prospective design justification or observed power. The registry gives assumptions for planning illustrations but does not report the trial’s own sample-size justification.

Finally, the record separates outcome reporting from safety reporting. Serious adverse event counts are available by listed group, but they cannot substitute for cognitive outcome results. Together, these features make the record a reminder that interpreting a clinical study requires a defined question, a transparent analysis plan, numerical estimates, and information about uncertainty and missing observations—not just a completed status and a named endpoint.

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 limitation for statistical interpretation is that the registry record does not report numerical results or analyses for the primary cognitive endpoint. It names a mean and standard error as the intended summary but provides no estimates or uncertainty intervals. The direction and size of any contrast therefore remain unknown.

The primary outcome is recorded as having several categories or time points, without reduction to one comparison. The registry does not identify which contrast was primary, how the medication and beverage conditions were combined, or how measurements across conditions or time points were analyzed. The statistical model, hypothesis tests, covariate adjustment, and any multiplicity approach are not reported in the registry record.

Participant flow, outcome-specific sample sizes, baseline characteristics, adherence, and missing-data procedures are also not reported. Although enrollment is listed as 44, the record does not explain how that enrollment relates to the safety groups’ at-risk counts. Masking is labeled triple, but the masked roles and allocation procedure are not specified.

The endpoint is a laboratory task measure, and the record describes it as an indicator of attention and response inhibition. Its meaning should not be extended beyond the task without additional evidence. The record’s safety counts are descriptive, and the absence of listed serious events does not establish a complete safety profile. Finally, the record provides no sample-size justification for the trial itself; the stated planning assumptions are illustrative rather than evidence of the original design rationale.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Varenicline on Fixed-Dose Alcohol Administration in Participants With Alcohol Use Disorders — NCT01000987.
• Registry record last updated 2018-02-19; status last verified 2018-01.
• Results first posted 2018-02-19.
• 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

NCT01000987 is a completed, randomized, triple-masked, parallel-model phase 2 study sponsored by Yale University. Enrollment is listed as 44. The study started in 2009-10, with primary completion in 2016-11. It examined varenicline at 1 mg/day or 2 mg/day versus placebo in participants with alcohol use disorders, in the context of alcohol or placebo-alcohol beverage administration.

The primary endpoint was the mean number of omissions on the CPT, following 3 weeks of medication and at 60 minutes after beverage consumption. The registry describes a high alcohol dose of 0.08 g/dL and attention to the ascending and descending limb of the blood alcohol curve. It reports no primary-outcome analyses or numerical results, and notes that the outcome’s categories or time points were not reduced to one comparison.

Safety listings show 0 serious adverse events and 0 deaths in each of the three listed groups. The registry does not report the analysis methods, missing-data procedures, analysis populations, or trial-specific sample-size justification.