This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effects of Aripiprazole on Cocaine Craving and Self-Administration (NCT00373880), a randomized phase 2 study. The primary outcome is Cocaine Self-administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00373880 |
| Phase | Phase 2 |
| Condition | Cocaine Abuse |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 26 |
| Arms in the primary outcome | 8 |
| Lead sponsor | New York State Psychiatric Institute |
| Results posted | Yes |
2. Clinical Question
The study asked whether aripiprazole changes cocaine self-administration, subjective effects, or craving compared with placebo. The primary outcome was the number of cocaine choices during a five-day measurement period. Participants sampled the cocaine dose available for a session and then chose between responding for money or cocaine using a modified progressive-ratio schedule.
Population
The condition listed was cocaine abuse. The trial enrolled 26 participants, while eight participants were included in the reported within-subjects analysis of cocaine choices. Further characteristics of the analyzed participants are not reported in the registry record.
Intervention
Aripiprazole at 15 mg/day was given in conjunction with a smoked cocaine dose-response curve. The tested cocaine doses were 0, 12, 25, and 50 mg.
Comparator
The comparator was placebo at 0 mg/day, also in conjunction with a smoked cocaine dose-response curve at 0, 12, 25, and 50 mg.
Primary question
Did the mean number of cocaine choices vary with cocaine dose and aripiprazole dose? The registry lists the outcome values but does not report an inferential test of the treatment comparison.
The study was randomized, double-masked, and used a crossover model. These features describe the intended design, but the registry record does not report treatment order, sequence allocation details, or the timing and length of treatment periods. The clinical question is therefore represented by the posted descriptive results, rather than by a reported estimate with a confidence interval or a test of the treatment effect.
3. Trial Design
This was a phase 2 randomized, double-masked crossover trial sponsored by New York State Psychiatric Institute. The listed condition was cocaine abuse. The record gives an enrollment of 26 and marks the study completed. The recorded start was 2005-04, and primary completion was 2008-08.
The intervention conditions paired aripiprazole or placebo with smoked cocaine doses of 0, 12, 25, and 50 mg. The aripiprazole dose is described as 15 mg/day, and placebo is described as 0 mg/day. The trial's brief summary says it was intended to investigate cocaine self-administration, subjective effects, and craving relative to placebo. The primary outcome reported in the results is cocaine self-administration, expressed as number of choices.
In a crossover design, participants generally receive more than one study condition, allowing comparisons within the same participant. This can reduce the influence of stable differences between participants. That general feature does not establish how this trial handled treatment sequence, period effects, or possible carryover; those details are not reported in the registry record. The registry identifies eight participants in the within-subjects analysis, but does not explain why the analyzed group was smaller than the enrollment figure or describe participant flow.
The primary outcome description says participants sampled the cocaine dose available for a session and then had five choices between money and cocaine under a modified progressive-ratio schedule. The outcome timeframe is listed as five days. The record does not provide further details about session scheduling, the exact analysis model, or how measurements across sessions were combined. Two secondary outcomes are listed: subjective effects of cocaine and plasma cocaine. Results for those outcomes 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
| Stage | Aripiprazole/Placebo, Cocaine |
|---|---|
| STARTED | 26 |
| COMPLETED | 8 |
| NOT COMPLETED | 18 |
Reasons for not completing this period:
| Reason | Aripiprazole/Placebo, Cocaine |
|---|---|
| Physician Decision | 3 |
| Arrested | 1 |
| Protocol Violation | 14 |
Analysis population for the primary outcome, as defined in the registry: Eight participants were included in this within-subjects analysis.
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.
| Characteristic | Unit | Aripiprazole vs. Placebo |
|---|---|---|
| Participants analysed | 8 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 41.8 (SD 3.9) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 8 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Cocaine Self-administration, measured over 5 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | Number of Choices |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean number of cocaine choices, measured as a function of cocaine dose and aripiprazole dose. It is a continuous outcome reported in units of number of choices. The registry describes the summary measure as a mean and its dispersion as a standard error. Eight participants were included in this within-subjects analysis, and the timeframe is five days.
Participants sampled the dose available for the session and then had five opportunities to respond for either money ($5.00) or cocaine. A modified progressive-ratio schedule governed those responses. The endpoint therefore records choices under the study's controlled choice task; it is not a direct count of cocaine use outside the study setting. The posted results should be interpreted in relation to this specific experimental measure.
Choice behavior is used in this study to operationalize self-administration: participants' responses indicate which option they selected within the task. Reporting the mean describes the average choice count at each listed dose condition. The standard error conveys uncertainty around an estimated mean, not the spread of individual participant values. The registry does not report individual data, a confidence interval for a treatment contrast, or a statistical test comparing aripiprazole with placebo. Thus, the endpoint values describe the observed group summaries but do not, by themselves, establish the precision or statistical significance of a treatment difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results are descriptive means for the number of cocaine choices, with standard errors. In the placebo condition, the reported means at 0, 12, 25, and 50 mg cocaine were 0, 1.5, 3, and 4 choices, respectively. In the aripiprazole condition, the corresponding means were 0.2, 2.8, 3.9, and 3.7 choices. Each listed condition has n=8. These summaries show how the reported mean choice count varied across the dose conditions; they do not constitute a reported statistical test.
At the nonzero cocaine doses of 12 mg and 25 mg, the reported means are higher in the aripiprazole condition than in the placebo condition. At 50 mg, the aripiprazole-condition mean is lower than the placebo-condition mean. At 0 mg, the means are 0 and 0.2, respectively. These are descriptive comparisons of the posted means, not adjusted or inferential estimates. No treatment contrast, confidence interval, or p value is reported in the registry record.
The standard errors are 0.5 for each placebo mean at 12, 25, and 50 mg, and 0.1 at 0 mg in the aripiprazole condition; the aripiprazole means at 12, 25, and 50 mg each have a standard error of 0.5. The placebo mean at 0 mg has a reported standard error of 0. These values summarize uncertainty around the means, but they do not directly describe the variability of individual choices. A standard error of 0 for a reported mean does not establish that there was no variation in every relevant aspect of the study data.
Because this was a crossover analysis, a treatment comparison would ordinarily need to account for the paired measurements and the design structure. The registry record does not give such an analysis. The record also indicates that values were missing or not estimable for a two-arm continuous-outcome comparison. Accordingly, no recalculated two-arm treatment estimate is presented. The posted means are the available basis for interpretation, and their pattern should not be treated as proof that aripiprazole increased or decreased cocaine choices.
The registry lists two secondary outcomes, subjective effects of cocaine and plasma cocaine, but does not report their results. It lists zero analysis records. That absence means the registry does not provide posted analysis details; it does not establish that no analyses were conducted outside the registry. Overall, the available results describe mean choice counts in eight participants across the listed conditions, without a reported inferential comparison or enough information to determine the uncertainty in a treatment effect.
9. Statistical Methods Explained
The posted primary outcome is a continuous measure: a mean number of choices. A mean gives a summary of the observed values by combining them into an average. It is useful for describing the typical level of a measure in a group or condition, but it can conceal differences among participants. The registry does not provide participant-level choice data, so the distribution of individual responses cannot be examined from the reported summaries alone.
What does the standard error describe?
The spread accompanying the reported means is identified as a standard error. In general, a standard error describes the precision of an estimated summary, such as a sample mean, under a statistical model. It is not the same as a standard deviation, which describes variability among observations. A smaller standard error generally indicates a more precise estimate, but its interpretation depends on the analysis and the data structure. The registry does not report a confidence interval for any mean or treatment contrast.
For a treatment comparison, an estimate is normally paired with an uncertainty measure and, where appropriate, a statistical test. A confidence interval gives a range of values compatible with the data and analysis under its assumptions; it helps readers assess both the direction and precision of an estimate. A p value addresses compatibility with a specified null hypothesis under a statistical model, but does not measure the size or clinical importance of an effect. Neither a treatment-comparison confidence interval nor a p value is reported in the registry record.
Why does the crossover design matter?
In general, crossover trials compare outcomes under multiple conditions within the same participant. This creates paired observations: a participant's response under one condition is related to that participant's response under another condition. A suitable analysis should reflect that pairing rather than treat all condition means as independent. The crossover structure can help separate treatment contrasts from stable differences between people, but it also makes period, sequence, and carryover considerations relevant. The record identifies a crossover model and eight participants in the within-subjects analysis, but does not report the statistical model, period handling, sequence details, or carryover assessment.
The repeated cocaine dose conditions also matter. The means are reported at four cocaine doses under each medication condition. A formal analysis could assess dose-related patterns and medication effects, but the record does not say whether such a model was fitted or what contrasts were planned. Describing changes across the displayed means is not a substitute for a test that accounts for repeated measurements and the study design.
What can be concluded from the posted summaries?
The summaries allow a descriptive reading of mean choice counts by condition. They do not provide the within-participant covariance, raw observations, or a treatment-effect estimate. Without those pieces, a paired uncertainty calculation cannot be recovered from the means and standard errors alone. The registry marks the continuous two-arm comparison as having values missing or not estimable, so no recalculated comparison is available. Since the discrepancy indicator is false, there is no recorded discrepancy between a sponsor analysis and a recalculation; in any case, the registry does not post a sponsor treatment analysis for this endpoint.
General statistical practice distinguishes descriptive summaries from inferential analyses. The means describe the observed outcome summaries. Inference would require an analysis plan and a model suited to the crossover and dose structure, along with information about missing observations and the analysis population. Those details are not reported in the registry record. The listed sample-size planning assumptions are an illustration based on an observed effect, not an observed-power calculation or evidence about the probability that this trial detected an effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect specified as a fraction of the observed effect. The registry does not report the trial's own sample-size justification or statistical plan.
Over-dispersion is a general concern when the variability of data exceeds what a chosen model assumes. If present, it can make standard errors from an overly restrictive model too small and make statistical evidence appear more precise than it is. The registry does not provide sufficient information to assess over-dispersion or to identify the model used for the endpoint. This is another reason to avoid interpreting the descriptive standard errors as if they were uncertainty estimates for a treatment contrast.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome, cocaine self-administration, and two secondary outcomes: subjective effects of cocaine and plasma cocaine. It also reports three outcome measures overall. Results are posted for the primary choice-count outcome, while results for the secondary outcomes are not reported in the registry record. The registry contains zero analysis records. This describes what is posted, not necessarily every analysis that may have been conducted.
When a study examines multiple outcomes, doses, or contrasts, the chance of obtaining at least one apparently notable result can increase if each is tested separately without accounting for the multiplicity. General methods for handling multiplicity include defining a primary comparison in advance, adjusting inference across a family of tests, or explicitly treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy of contrasts, or which dose-specific comparisons were planned. No claim about adjustment can therefore be made.
The reported primary analysis includes eight participants in a within-subjects analysis. The registry does not explain how this analysis population relates to the enrollment of 26, give participant flow, or report whether any endpoint observations were missing. It does not describe imputation, exclusion rules, or a sensitivity analysis. These matters are not reported in the registry record.
Missing outcome data can affect both the estimated mean and the precision of an analysis, depending on why data are absent and how missingness is handled. In a crossover study, missing measurements in one condition can also affect the paired comparison. Here, the registry notes that values were missing or not estimable for a two-arm continuous-outcome comparison, but it does not identify a treatment contrast that could be interpreted or explain the underlying reason. The posted descriptive values should therefore be read without assuming complete follow-up, a particular missing-data method, or an intention-to-treat analysis population.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Aripiprazole vs. Placebo | 0 | 8 | 0.0% |
| Placebo | 0 | 8 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Aripiprazole vs. Placebo | 0 of 8 |
| Placebo | 0 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Aripiprazole vs. Placebo | 0 of 8 |
| Placebo | 0 of 8 |
The registry lists two safety groups: “Aripiprazole vs. Placebo” and “Placebo.” For the first group, 8 participants were at risk for serious adverse events and 0 were reported as affected; 8 were at risk for other adverse events and 0 were reported as affected. For the placebo group, 8 participants were at risk for serious adverse events and 0 were reported as affected; 8 were at risk for other adverse events and 0 were reported as affected. Deaths are reported as 0 in both groups, and no top serious-event terms are listed.
These are counts in the registry record, not estimates of the probability of an event outside this study. A zero count means no events were recorded in the listed group and category; it does not show that the underlying risk is zero. The small analyzed groups and the registry's limited safety detail constrain what can be inferred. The record does not report event narratives, follow-up duration for safety, or a fuller account of event collection and attribution. The group label should be read as recorded, without assuming further details about exposure periods or how the crossover safety data were assigned.
12. What the Result Does, and Does Not, Mean
The results describe mean cocaine-choice counts across cocaine doses during aripiprazole and placebo conditions. They show different descriptive patterns across the dose conditions: the aripiprazole means are higher at 12 mg and 25 mg, lower at 50 mg, and close to the placebo mean at 0 mg. The reported means and standard errors characterize the summaries for the eight participants included in the within-subjects analysis.
These findings do not establish whether the treatment conditions differ statistically. The registry does not report a treatment-effect estimate, confidence interval, p value, or inferential analysis for the primary outcome. The pattern across means alone cannot determine whether apparent differences are consistent within participants, sufficiently precise, or attributable to the medication condition rather than other design or measurement factors. A crossover analysis would need to use the paired structure and relevant design details, which are not posted.
The endpoint is a choice task conducted under specified study conditions. It does not, by itself, measure behavior outside the study setting or establish effects on every aspect of cocaine use. The stated study purpose also included subjective effects and craving, but the posted secondary outcomes are subjective effects of cocaine and plasma cocaine, and their results are not reported in the registry record. No conclusions about those outcomes can be drawn from the primary choice-count summaries.
The safety record reports zero serious adverse events, zero other adverse events, and zero deaths in each listed group. Such counts should not be interpreted as proof that events cannot occur. The registry's counts provide a limited description of the recorded safety results for the listed groups, not a complete characterization of possible harms.
In short, the posted record offers descriptive primary-outcome data and limited safety counts, but no reported inferential treatment comparison. It supports careful description of the observed summaries, not a definitive claim about the effect of aripiprazole on cocaine self-administration, subjective effects, or craving.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its primary question is studied with a crossover design and a repeated dose-response task. The same participant can contribute measurements under different study conditions, which creates a natural paired structure. Properly representing that structure can be important for precision, but the registry record does not provide the treatment sequence, the period-level data, or the model used. Readers can see the condition-specific means without being able to reconstruct the intended inferential comparison.
The reported values also make clear why a single summary across conditions would be inadequate. Mean choice counts differ across the four cocaine doses, and the descriptive pattern is not uniform between medication conditions. A statistical analysis would need to specify which medication and dose questions are of interest and how repeated observations are handled. The registry does not report planned contrasts or multiplicity procedures, so the means should not be treated as a complete account of the analysis.
Another important distinction is between sample size and analysis population. The record gives enrollment of 26 but identifies eight participants in the within-subjects primary analysis. Without participant flow or an explanation of the analytic population, readers cannot determine how that relationship arose. This illustrates why a trial record is most informative when it reports both enrollment and outcome-specific denominators, along with exclusions and missing-data handling.
Finally, a mean and its standard error are not a substitute for a treatment-effect estimate and confidence interval. The posted summaries offer a useful descriptive view, yet do not quantify the uncertainty in the within-person treatment contrast. The registry's missing or non-estimable two-arm comparison further limits recalculation. The result is a record that supports examination of design and reporting questions while leaving the main inferential question unresolved in the posted data.
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 primary limitation for interpreting the treatment question is the absence of a reported inferential comparison. The registry gives condition-specific means and standard errors but no estimate of the within-subject treatment effect, confidence interval, or p value. It also notes that values were missing or not estimable for a two-arm continuous-outcome comparison. Consequently, the descriptive pattern cannot establish the size or precision of a treatment difference.
The outcome analysis includes eight participants, whereas enrollment is reported as 26. The registry does not explain the difference, provide participant flow, or describe exclusions and missing observations. It is therefore not possible to determine from the record how the analysis population was selected or how representative it was of those enrolled. The record also does not report an analysis population definition or missing-data procedure.
Important crossover details are not reported, including treatment order and the handling of period or carryover effects. The model used for repeated dose conditions is also not described. These omissions matter because a treatment comparison should reflect paired measurements and the structure of the repeated observations. The registry does not provide participant-level data or the covariance information needed to independently reconstruct that analysis.
The study's listed secondary outcomes do not have posted results, and the registry does not describe multiplicity handling or the planned contrasts. Safety reporting is limited to the event counts shown in the record, with no top serious-event terms listed. Finally, the trial's own sample-size justification and statistical plan are not reported in the registry record. These limitations concern the information available in the registry and do not establish what may have been reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effects of Aripiprazole on Cocaine Craving and Self-Administration — NCT00373880.
- Registry record last updated 2017-09-11; status last verified 2017-09.
- Results first posted 2017-09-11.
- 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.
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18. Record Summary
This completed phase 2 study was randomized, double-masked, and used a crossover model. It enrolled 26 participants and examined aripiprazole at 15 mg/day versus placebo during smoked cocaine dose-response sessions at 0, 12, 25, and 50 mg. The primary outcome was mean number of cocaine choices over five days; eight participants were included in the within-subjects analysis.
The registry reports condition-specific means and standard errors but no inferential treatment comparison. It lists subjective effects of cocaine and plasma cocaine as secondary outcomes without reporting their results. The safety record reports zero serious adverse events, zero other adverse events, and zero deaths in each listed group. Treatment sequence, analysis details, missing-data handling, and the trial's statistical plan are not reported in the registry record.