Effects of Tolcapone on Decision Making and Alcohol Intake in Alcohol Users: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Tolcapone on Decision Making and Alcohol Intake in Alcohol Users (NCT02740582), a randomized phase 2 study. The primary outcome is Number of Drinks Consumed in a Laboratory Bar Session.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, triple-masked, crossover study. The registry lists enrollment as 62 and status as completed. Its stated purpose was to examine tolcapone’s effects on decision making and alcohol intake using a laboratory bar, described as on-site alcohol self-administration, in alcohol drinkers. The official title specifies moderate to heavy social drinkers.

The two treatment sequences were tolcapone followed by placebo, or placebo followed by tolcapone. The tolcapone period is described as 5 days of 100 mg tolcapone TID; the placebo period is described as 5 days of placebo. A washout period separated the periods in either sequence. The duration and operational details of washout are not reported in the registry record. The registry does not describe the randomization procedure, allocation concealment, masking procedures, or how adherence was assessed.

In a crossover design, participants receive more than one treatment in sequence, allowing outcomes under different treatments to be compared within the same participant. This general design can account for stable differences between participants, but interpretation depends on the conduct and analysis of the treatment periods. The registry does not report how period effects, sequence effects, or possible carryover were handled in the analysis.

The recorded primary outcome was the number of drinks consumed during a 1-hour laboratory bar session following either treatment. The outcome description states that a maximum of 4 drinks was available. The record says completers were analyzed, but does not give the number completing both periods or explain how incomplete treatment sequences were handled. The study dates are recorded as start on 2016-10-01 and primary completion on 2019-09-01.

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.

First Intervention

Washout

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Completers were analyzed

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: Completers of study were used for analysis

6. Primary Endpoint

The registry lists the primary outcome as Number of Drinks Consumed in a Laboratory Bar Session, measured over A laboratory bar session is 1 hour long.

The primary endpoint is the number of drinks consumed in a laboratory bar session lasting 1 hour. The registry describes the session as an on-site alcohol self-administration setting and says that up to 4 drinks were available. The measure is a count of drinks consumed, although the outcome is classified in the registry as continuous and its summary parameter as a mean with standard deviation.

The endpoint was used to assess alcohol intake under the two treatment conditions in a controlled laboratory setting. Such a measure captures consumption during the defined session, rather than alcohol use across everyday settings or over an extended period. The record’s stated primary outcome therefore addresses behavior in that laboratory context. It does not, by itself, describe longer-term drinking patterns.

The registry does not report the mean number of drinks for either treatment, the variability of those results, or a treatment contrast. It also does not report a confidence interval or a test of the difference. The outcome is described as following either placebo or tolcapone administration, and the analysis population is identified as completers. Further details about the outcome’s scoring, distribution, or handling of participants who did not complete a session are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record classifies the primary outcome as continuous, summarizes it by a mean, and identifies standard deviation as the measure of dispersion. No numerical means or standard deviations are reported. The general statistical concepts below explain how these quantities and common comparison methods are interpreted; they do not describe an analysis that can be confirmed from this registry record.

What does a mean describe?

In general, a mean is the arithmetic average of measured values. For this endpoint, the measured quantity is the number of drinks consumed during a laboratory session. A mean can provide a compact description of consumption across participants, but it does not show how individual values are distributed. If many participants have similar values, the mean may be representative of most observations; if values vary substantially, the same mean can conceal a wider range of individual responses. The registry does not report the observed means for either treatment period.

What does the standard deviation describe?

In general, the standard deviation describes the spread of observations around their mean. It is a descriptive measure of participant-to-participant variability, not a measure of uncertainty in the estimated mean. Uncertainty in a treatment comparison is usually conveyed separately, for example with a confidence interval. A confidence interval represents a range of values compatible with the data and the method’s assumptions; it is not a guarantee that the true effect lies in that range. The registry does not report standard deviations or confidence intervals for this outcome.

Why does the crossover design matter?

In general, a crossover trial measures participants under multiple treatment conditions, in a specified sequence. Because measurements from one participant are likely to be related, a method that accounts for within-participant pairing may be appropriate. A comparison that treats all observations as independent may fail to represent that relationship. The record confirms a crossover model and two treatment sequences but does not report the specific statistical model or whether the treatment comparison used paired observations.

Period and sequence can also matter in a crossover study. A period effect is a difference associated with when a measurement occurs, regardless of the assigned treatment. A sequence effect is a difference related to the order in which treatments are received. Carryover refers generally to an influence of an earlier treatment persisting into a later period. A washout is intended to separate treatment periods, but its presence alone does not establish that carryover was assessed or absent. The record states that a washout period occurred, while its duration and the handling of period, sequence, and carryover effects are not reported in the registry record.

How should a treatment comparison be read?

In general, an estimated contrast describes the difference between treatment conditions according to a specified analysis. The estimate’s scale and interpretation depend on the outcome and model. For this trial, the outcome is a number of drinks, but the registry does not report a contrast or analysis result. A p-value, if reported, would address compatibility with a statistical null hypothesis under the analysis assumptions; it would not describe the size or practical importance of a contrast. A confidence interval would add information about precision. Neither a p-value nor a confidence interval is reported for the primary outcome.

Distributional assumptions also matter. In general, count outcomes can have features such as skewness, bounds, or variance that differs from the mean. The endpoint is bounded by the maximum number of drinks available in the session, while the registry classifies it as continuous and specifies a mean and standard deviation. That classification records the planned or reported outcome format, but does not reveal the observed distribution or establish which statistical model was used. The registry does not report distributional checks or a model choice.

What can sample-size planning illustrations establish?

In general, a sample-size calculation describes the number of participants that a hypothetical design would require under stated assumptions. It is not a result from participants in the trial, and it is not observed power. The registry gives planning assumptions based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not report numerical outputs for these planning illustrations. The trial’s own sample-size justification is not reported in the registry record. The planning assumptions therefore cannot be used to infer what the trial was designed to detect or whether its completed sample was adequate for a particular effect.

The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. It reports zero analyses. Consequently, no analysis method, adjustment strategy, or outcome-specific statistical result can be verified from the record. General principles about means, uncertainty, and crossover analysis should not be mistaken for evidence that a particular method was used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, but notes that the primary outcome has several categories or time points and was not reduced to one comparison. It does not identify the category- or time-specific estimates, nor does it report how comparisons across those categories or time points were handled. The analysis count is zero. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or a prespecified approach for choosing among comparisons.

Multiplicity is a general statistical concern when multiple hypotheses or comparisons are evaluated: the chance of at least one apparently notable result can increase as the number of tests grows. Adjustments or prespecified testing strategies can address this concern, but no such approach is described in the registry record. Without the detailed results and analysis plan, the extent of multiplicity and its handling cannot be assessed.

The primary outcome population is described as completers. The number of completers, reasons for noncompletion, missing outcome counts, and methods for handling missing data are not reported in the registry record. It is also not reported whether the analysis included participants with incomplete treatment sequences or used any imputation method.

The study was randomized and crossover, but the record does not state whether analysis followed an intention-to-treat principle, a per-protocol principle, or another defined population. Completers were analyzed is the only reported population description for the primary outcome. It should not be assumed that all 62 enrolled participants contributed data to both treatment conditions. The number contributing to the primary comparison is not reported in the registry record.

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 5% reporting threshold.

The registry reports zero serious adverse events among 60 participants at risk in the tolcapone group and zero among 57 participants at risk in the group labeled “Placebeo.” It also reports zero deaths in each group. The other adverse-event counts are recorded as zero among 60 and 57 participants, respectively. The label “Placebeo” is the spelling used for that group in the registry record.

These figures describe the listed risk sets and recorded events; they do not supply a detailed safety profile. The registry does not list serious adverse-event terms, and it does not report event timing, duration, severity beyond the serious-event category, or reasons for the different risk-set sizes. The counts should not be interpreted as evidence that no adverse events of any kind occurred, because the record’s displayed categories and event definitions are limited. Nor should the risk-set counts be assumed to be the number analyzed for the primary endpoint.

The trial used a crossover design, but the adverse-event listing is organized by treatment group. The registry does not explain how participants who received both treatments were represented in these risk sets or how events were attributed to treatment. The displayed figures can therefore be reported as recorded, without inferring comparative safety or assigning a causal interpretation.

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

The registry record establishes the study question, treatment sequences, and the laboratory measure chosen as the primary outcome. It describes a randomized, triple-masked crossover comparison of tolcapone and placebo in alcohol users, with a laboratory bar session lasting 1 hour and up to 4 drinks available. These design details identify the setting and intended comparison.

The record does not provide the numerical results for drinks consumed, a treatment contrast, a confidence interval, or a p-value. It therefore does not establish from the posted results whether consumption differed between the treatment conditions, how large any difference was, or how precise an estimate might be. A completed status does not fill that gap.

The measured behavior is consumption during a laboratory session. General interpretation should remain specific to that setting and outcome. The registry does not report results for drinking outside the laboratory, longer-term outcomes, or decision-making measures. Although decision making appears in the study title and stated purpose, no numerical decision-making result is included in the record summarized by the primary outcome information.

The design may support within-participant comparisons in principle, but the actual analysis is not reported. The record does not explain how the crossover sequences, repeated measurements, missing data, or multiple categories and time points were handled. Accordingly, the design alone cannot establish the validity or precision of a treatment estimate that is not reported.

The appropriate conclusion from the registry information is limited: the trial was completed and was intended to compare a defined laboratory alcohol-intake outcome after tolcapone and placebo. The registry record does not report the outcome findings needed to characterize the direction, magnitude, or uncertainty of that comparison. No claim about a treatment effect should be inferred from enrollment, completion status, or the adverse-event counts.

13. Why This Trial Matters Statistically

This trial is statistically notable for its crossover structure and a behavioral endpoint measured in a controlled laboratory setting. Each sequence included both tolcapone and placebo periods, separated by washout. In general, crossover designs can use within-participant information, but this structure also makes the timing and analysis of measurements important. The registry describes the sequence arrangement without reporting how the analysis accounted for it.

The outcome is a bounded count of drinks consumed during a 1-hour session, yet the registry classifies it as continuous and specifies a mean and standard deviation. That combination makes the reported outcome definition and the analysis method important to interpretation. The record does not provide the observed distribution or explain the statistical model, so the adequacy of any particular approach cannot be evaluated.

The record also illustrates the difference between recording an endpoint and reporting an analyzable result. It names the primary outcome and says completers were analyzed, but provides no numerical outcome comparison. It notes several categories or time points and no single reduced comparison, and it lists zero analyses. Without estimates and uncertainty, readers cannot judge precision or assess how the results relate to the stated question.

Finally, the presence of planning assumptions does not provide a trial-specific sample-size justification or an outcome conclusion. General planning illustrations are distinct from observed results and do not establish observed power. In this case, the registry does not report numerical illustration outputs or the trial’s own sample-size justification. These distinctions matter when interpreting what a registry entry can—and cannot—support.

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 central limitation of the registry record is the absence of numerical results for the primary endpoint. It does not report treatment-specific means, standard deviations, an estimated contrast, or an uncertainty interval. The note that the outcome has several categories or time points and was not reduced to one comparison further means that no single primary comparison is presented.

Important details for assessing the analysis are also not reported in the registry record. These include the number of participants completing both periods, the handling of missing observations, the statistical model, and the treatment of period, sequence, and possible carryover effects. The record says completers were analyzed, but does not define the completeness requirement or account for participants who did not complete.

Generalizability is limited by the setting and outcome described: a laboratory session measuring drinks consumed over 1 hour. The record does not report longer-term alcohol-use outcomes or results outside this setting. Detailed eligibility criteria and the characteristics of participants are not reported in the registry record, so the sample cannot be further characterized from this information.

The registry’s adverse-event counts are limited to the categories shown and do not include serious adverse-event terms. The reasons for the risk-set sizes and the attribution of events in the crossover design are not described. These omissions limit interpretation of the safety figures as well as the primary outcome information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Tolcapone on Decision Making and Alcohol Intake in Alcohol Users — NCT02740582.
• Registry record last updated 2020-09-21; status last verified 2020-09.
• Results first posted 2020-09-21.
• 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.

18. Record Summary

NCT02740582 is a completed Phase 2 randomized, triple-masked crossover study titled “Effects of Tolcapone on Decision Making and Alcohol Intake in Alcohol Users.” The official title specifies moderate to heavy social drinkers. Enrollment was 62; the recorded start date is 2016-10-01, and primary completion is 2019-09-01.

Participants were assigned to tolcapone followed by placebo, or placebo followed by tolcapone, with a washout period. The tolcapone period is described as 5 days of 100 mg TID. The primary outcome was the number of drinks consumed in a 1-hour laboratory bar session, with up to 4 drinks available; completers were analyzed.

The registry does not report numerical primary-outcome results or an analysis result. It lists zero serious adverse events and zero deaths in the displayed treatment groups. The trial’s sample-size justification, detailed missing-data approach, and specific statistical analysis are not reported in the registry record.