D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement (NCT02203786), a randomized phase 2 study. The primary outcome is Subjective Reinforcement Self-report Scales.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, triple-masked, parallel phase 2 trial, with an enrollment of 60. Its listed condition is pathological gambling, and the study title and summary describe both pathological gamblers and healthy controls. The trial status is completed. The recorded start is 2009-09 and primary completion is 2015-06.

The listed drug interventions are haloperidol, fluphenazine, Dexedrine, and placebo. The behavioral intervention is a slot-machine task. The partial arm descriptions state that participants were randomized to sequences involving haloperidol or fluphenazine on day 1 or day 2 of each phase. Because those descriptions are cut off, they do not establish the complete treatment schedule, all dose details, or how every intervention was assigned. The record calls the model parallel, so the sequence wording should not be used to infer a different design.

Triple masking indicates that masking was part of the registered design, but the identities of the groups kept masked and the procedures used to maintain masking are not reported in the registry record. The record also does not report the randomization method, allocation concealment procedure, site count, eligibility criteria, or a full account of participant flow. These omissions limit how far the design can be reconstructed from the registry information alone.

The study’s stated aims were to examine whether gambling and stimulant reinforcement have parallel dopamine-receptor roles, and whether those roles are associated specifically with gambling pathology or appear in both gamblers and controls. The registry lists secondary outcomes involving blood pressure, cognitive-task performance, slot-machine betting behavior, speed of play, and winnings. It does not report a complete analysis plan linking each outcome and time point to a specific treatment contrast.

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.

Before assignment: Pathological Gamblers and healthy Controls were each randomized to receive Haloperidol or Fluphenazine. In each group, treatment sequence (antagonist first, placebo second; or vice versa) was counterbalanced across participants, to control for order effects only (sequence was not a test factor). Two Haloperidol-Controls dropped out after session 1.

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.

Population: All participants were above 18 years of age.

6. Primary Endpoint

The registry lists the primary outcome as Subjective Reinforcement Self-report Scales, measured over At key points in testing: immediately after the slot machine game, and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)..

The primary outcome is a set of single-item visual analogue ratings of self-reported confidence to refrain from gambling. Ratings range from 0 to 10 units on a scale. A score of 10 denotes complete confidence to refrain, described as no urge or compulsion to gamble; a score of 0 denotes complete lack of confidence, described as an overwhelming urge. Intermediate values represent intermediate confidence, with lower scores indicating less confidence and greater urge or compulsive motivation to gamble.

The record describes measurements at baseline, before and after the slot-machine game in Phase 1, and before amphetamine and at peak amphetamine in Phase 2. Its outcome timeframe also identifies assessment immediately after the slot-machine game and at expected peak subjective-behavioral effects for amphetamine, 90-minutes post-capsule administration. The reported summary measure is the mean and standard deviation of the individual ratings for each subgroup.

As a self-report measure, this endpoint captures participants’ stated confidence or urge at specified testing points. It is not itself a direct measure of gambling behavior, winnings, or a clinical diagnosis. The registry does not report numerical values for the ratings, their variability, or comparisons between groups and conditions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered outcome is continuous: each participant supplies a numerical rating on a 0-to-10 scale, and the registry describes subgroup means and standard deviations. The record does not report the values of those means or standard deviations, nor any estimated treatment contrasts. Consequently, the statistical methods can be discussed only as general concepts and as questions that would matter for interpreting this design, not as a description of analyses known to have been conducted.

What does a mean and standard deviation convey?

General statistical explanation: the mean gives the arithmetic center of a set of ratings. The standard deviation describes how dispersed the ratings are around that center. Together they can help readers understand both the typical reported rating and the variation among participants. They do not show the full distribution, and the same mean and standard deviation can arise from different patterns of individual responses. The record specifies these summary measures but does not provide their numerical results.

Why do the testing points matter?

The endpoint is assessed at multiple points related to the slot-machine game and amphetamine testing. A comparison of subgroup means at one point answers a different question from a comparison of changes across points. Repeated observations from the same participant are generally statistically dependent: an individual’s ratings may be related across assessments. General statistical explanation: analyses of repeated measurements need to account for that dependence when estimating uncertainty. The registry record does not report whether a repeated-measures model, a change-score approach, or another method was used.

The timing descriptions also make the target of each contrast important. A rating after the slot-machine task concerns a different testing context from a rating at expected peak amphetamine effects. Combining those assessments into one summary without a clear rationale could obscure context-specific patterns. The registry record does not report a single primary contrast or explain how the multiple time points are intended to be synthesized.

How should treatment contrasts be defined?

General statistical explanation: a treatment contrast is the specific comparison an analysis estimates, such as a difference between two defined conditions in a defined population and at a defined time. Clear contrasts are needed to distinguish the effect of a drug from differences associated with participant group, testing context, or sequence. The record lists haloperidol, fluphenazine, Dexedrine, placebo, and the slot-machine task, and it describes day-based drug sequences in partial arm descriptions. It does not report the complete allocation structure or a full list of planned contrasts. No particular pairwise comparison should therefore be assumed.

The trial is registered as randomized, triple-masked, and parallel. General statistical explanation: random allocation can support fair comparisons when implemented and preserved, while masking can reduce some forms of expectation or assessment bias. Those design labels do not by themselves establish how randomization and masking were carried out or whether they remained intact. The procedures are not reported in the registry record.

What do confidence intervals and tests contribute?

General statistical explanation: a confidence interval communicates the range of effect estimates compatible with the data under a statistical model and its assumptions. It can show whether the estimate is precise or uncertain and whether a range of magnitudes remains plausible. A significance test addresses a narrower question about data compatibility with a null hypothesis. Neither a p-value nor an interval should be interpreted without the estimate, the comparison being made, and the analysis assumptions. The record reports no primary-outcome estimates, confidence intervals, or hypothesis tests.

Over-dispersion is a general concern when observed variability exceeds what a chosen statistical model assumes. If a model understates variability, standard errors may be too small and uncertainty may appear lower than it is. This concept is relevant to statistical modeling generally, but the registry record does not report a model for these ratings or evidence of over-dispersion. It would be inappropriate to claim that over-dispersion occurred in this trial.

What can planning calculations tell readers?

General statistical explanation: sample-size planning estimates how many participants may be needed to detect a chosen effect under stated assumptions. Such calculations depend on the target effect, variability, significance level, allocation, and model assumptions. They are planning illustrations, not observed power and not evidence that an effect occurred. The registered enrollment is 60. The record does not report the trial’s own sample-size justification. Any planning illustration based on an observed effect should be read as a hypothetical planning exercise, not as a design rationale or a measure of the trial’s success.

The listed planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of an observed effect. The registry record does not report the trial’s own design justification or a statistical plan that validates those assumptions for its multiple groups and assessment times. No planning result should be treated as observed evidence.

What information is needed to assess an analysis?

General statistical explanation: readers need the analysis population, participant counts for each comparison, treatment contrast, handling of repeated observations, missing-data approach, and uncertainty estimates to judge an analysis. They also need to know whether reported analyses follow prespecified methods or are exploratory. The registry indicates zero reported analyses. It does not report those details for the primary outcome. Thus, statistical properties such as adjustment, model fit, robustness, and the handling of withdrawals cannot be evaluated from the record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome has several assessment points across the slot-machine and amphetamine testing phases. The registry identifies the outcome as a set of ratings rather than a single comparison, and explicitly indicates that it was not reduced to one comparison. Multiple outcomes are also listed: the primary subjective rating and secondary measures covering blood pressure, cognitive-task performance, betting behavior, speed of play, and winnings. The registry lists six outcome measures and zero analyses.

General statistical explanation: when many outcomes, time points, groups, or contrasts are examined, the chance of at least one apparently notable result can increase. A statistical plan may address this through a prespecified primary contrast, adjustment procedures, or a clear distinction between confirmatory and exploratory analyses. The multiplicity strategy and prespecified contrast are not reported in the registry record, so the degree to which multiple testing was addressed cannot be assessed.

The registry record does not report missing-data counts, reasons for missingness, or methods used to handle missing observations. General statistical explanation: missingness can affect estimates if participants with observed data differ systematically from those without data. The consequences depend on the pattern of missingness and the analysis assumptions. Without participant flow and a stated missing-data method, the potential impact on the outcome estimates cannot be evaluated.

The record does not define the analysis populations, such as whether analyses were intended to include all randomized participants or a restricted subset. It also does not report how exclusions, protocol deviations, or incomplete assessments were handled. These details are important for interpreting randomized comparisons, and are not reported in the registry record.

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 registry lists serious adverse events for four groups: haloperidol in pathological gamblers, fluphenazine in pathological gamblers, haloperidol in controls, and fluphenazine in controls. Each group has 15 participants at risk. No serious adverse events are reported as affecting participants in any of these groups. The deaths fields are null, so deaths are not reported in the registry record.

For other adverse events, the registry reports zero affected participants in the haloperidol and fluphenazine pathological-gambler groups, two affected participants in the haloperidol control group, and zero in the fluphenazine control group. Each group lists 15 participants at risk. The record does not identify the terms for these other events, so their nature and severity cannot be assessed from this information.

These are counts recorded for the listed groups, not proof that an intervention caused or did not cause an event. The registry record does not report event-level details, timing, duration, relatedness assessments, or exposure-adjusted analyses. The absence of a reported serious event in these groups should be interpreted as a description of the posted safety data, not as evidence that risk is absent.

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

The registry record establishes that a completed randomized, triple-masked, parallel phase 2 trial addressed dopamine antagonists, gambling-related ratings, and stimulant reinforcement in pathological gamblers and healthy controls. It also defines the primary rating and lists additional behavioral, cognitive, and blood-pressure outcomes. These details explain the intended research question and how one aspect of it was measured.

They do not establish the direction or magnitude of any outcome. Numerical primary-outcome results, treatment-effect estimates, uncertainty intervals, and statistical tests are not reported in the registry record. The reported endpoint description therefore cannot show whether ratings differed across conditions or participant groups. It also cannot establish whether any observed pattern would be precise, robust, or clinically meaningful.

The endpoint is self-reported confidence to refrain from gambling at specified testing points. It should not be treated as interchangeable with actual betting behavior, speed of play, winnings, or a broader assessment of gambling pathology. Those are distinct constructs, even though the registry lists some of them as secondary outcomes. Their results are not reported in the registry record.

General statistical explanation: an association between a rating and a testing condition would not by itself prove a mechanism involving a dopamine receptor. Mechanistic interpretation requires a well-defined comparison and evidence that competing explanations are addressed. Likewise, differences between pathological gamblers and controls would need estimates and uncertainty for the relevant contrasts. The registry record does not report analyses that support either conclusion.

The safety counts describe reported affected participants in the listed groups but do not establish causation or rule out unreported events. Overall, the record supports a cautious account of the trial’s aims, design labels, measurement schedule, and posted adverse-event counts. It does not support a conclusion that a treatment did or did not work.

13. Why This Trial Matters Statistically

Statistically, this trial raises questions that are more complex than a single comparison of two group means. The stated aims involve two participant groups, drug interventions, a placebo, gambling and amphetamine testing contexts, and repeated ratings. Its secondary outcomes include both self-report and behavioral measures. These features make clear definitions of the target comparison and outcome timing important for interpreting any analysis.

The primary endpoint is meaningful as a direct report of confidence to refrain from gambling, but its interpretation depends on direction and context. Higher ratings indicate greater confidence, while lower ratings indicate less confidence and greater reported urge. The registry describes measurements around the slot-machine task and amphetamine testing, making it important to distinguish those settings rather than assume that one rating captures all aspects of reinforcement.

General statistical explanation: when a study has several groups, outcomes, and assessment times, a prespecified analysis plan helps readers distinguish the main hypothesis from exploratory comparisons. It also helps explain how uncertainty and multiplicity are handled. In this record, the outcome structure is described but a statistical analysis plan and numerical analyses are not reported. That absence illustrates why a trial’s registered question and completed status cannot substitute for results.

The record also illustrates the importance of complete reporting. The enrollment and design labels are available, but the full treatment schedule, analysis population, missing-data handling, and treatment contrasts are not. Such details affect how readers assess the credibility and scope of estimates when results are available. In their absence, the appropriate statistical contribution is to clarify what was intended to be measured and what remains unanswered by the registry record.

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 principal limitation for interpreting this specific trial from the registry record is the absence of numerical primary-outcome results and inferential analyses. Although the primary rating is defined in detail, the record does not report subgroup means, standard deviations, contrasts, confidence intervals, or p-values. The stated aims therefore cannot be evaluated from the posted outcome information.

The design description is incomplete in important respects. The registry identifies a randomized, triple-masked, parallel model and gives partial descriptions of randomized drug sequences, but the arm descriptions are truncated. Full dosing, schedule, intervention allocation, and masking procedures are not reported in the registry record. This prevents a complete reconstruction of the participant experience and intended comparisons.

Several assessment points and outcomes are listed, but the specific primary contrast and multiplicity strategy are not reported. The analysis population, participant flow, missing-data approach, and handling of repeated observations are also not reported in the registry record. Without these details, the impact of incomplete assessments and the appropriateness of any model cannot be assessed.

The listed adverse-event counts lack event terms and detailed context for the two other adverse events in the haloperidol control group. Serious events are reported as zero affected participants in the listed groups, while deaths are not reported in the registry record. These limited summaries do not provide a full safety profile or establish causality.

Finally, the record’s outcome definitions alone cannot establish receptor mechanisms or generalize beyond the studied populations and testing contexts. The registry does not report eligibility details or a complete account of recruitment and participant flow. Conclusions should therefore remain limited to the design and measurements documented, rather than claims about treatment effects or broader clinical meaning.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement — NCT02203786.
• Registry record last updated 2016-04-25; status last verified 2016-04.
• Results first posted 2016-04-25.
• 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

NCT02203786 is a completed randomized, triple-masked, parallel phase 2 trial with an enrollment of 60. It concerns pathological gamblers and healthy controls and examines D2 and mixed D1-D2 dopamine antagonists in relation to gambling and amphetamine reinforcement. Listed interventions include haloperidol, fluphenazine, Dexedrine, placebo, and a slot-machine task.

The primary outcome is self-reported confidence to refrain from gambling, summarized as subgroup means and standard deviations at testing points around the slot-machine game and amphetamine administration. The record lists secondary measures involving blood pressure, cognition, and slot-machine behavior. It does not report primary-outcome estimates, statistical analyses, the full analysis plan, or a complete treatment schedule. Serious adverse events are reported as affecting no participants in the four listed groups; deaths are not reported in the registry record.