Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence (NCT00376558), a non-randomized na study. The primary outcome is Change From Baseline in the Binding Potential of [11C]Raclopride.

2. Clinical Question

In general, a study question can concern either a treatment effect or a relationship between a biological measure and an outcome. Those are different aims. A treatment-effect question asks what would happen under one treatment compared with another, whereas an association question asks whether measured characteristics and outcomes vary together. The registry describes both imaging over time and relationships with treatment response, but it does not report numerical estimates for those relationships or for change in the primary measure.

The record identifies cocaine dependence as the condition and describes an intervention combining Contingency Management with the Community Reinforcement Approach. It does not describe random assignment: allocation is listed as non-randomized. Healthy controls were included as matched comparison subjects, but they are not described as receiving the behavioral treatment. Consequently, differences between the cocaine-user and healthy-control groups cannot by themselves isolate a treatment effect. The questions that can be addressed depend on the particular analysis, its participant population, and the results reported; those numerical results are not reported in the registry record.

3. Trial Design

This was a completed, parallel, non-randomized study with no masking. The registry lists an enrollment of 50 and identifies New York State Psychiatric Institute as the sponsor. The listed study dates are 2006-07 for start and 2010-07 for primary completion. The phase is listed as NA. The study is titled “Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence.”

The record describes cocaine users receiving Contingency Management with the Community Reinforcement Approach and a group of healthy matched comparison subjects. The healthy subjects were matched for cigarette smoking, gender, and ethnicity, and the arm description states that they had no DSM-IV axis I disorder. The intervention type is behavioral. A non-randomized allocation means the record does not describe participants being assigned by chance to treatment groups. No masking means the design is not listed as blinded. The registry does not report further procedures for allocating participants or maintaining masking.

The primary outcome concerns change in the binding potential of [11C]Raclopride, with measurements at baseline and 3 months. The description links methylphenidate-induced dopamine release in the striatum, measured by displacement of [11C]-Raclopride following oral methylphenidate, with treatment response measured using the behavioral approach and contingency management. The record also lists cocaine craving, withdrawal symptoms, and pattern of cocaine use as secondary outcomes. It lists two outcome measures and two analyses, but does not describe the full analysis plan or provide numerical results for the primary measure.

Enrollment and analysis populations should not be treated as interchangeable. The primary outcome description says 24 cocaine users were included in the change analysis because one participant had baseline scanning only, while treatment data for all 25 cocaine users were used. The safety record lists 24 cocaine users and 25 control subjects at risk for the event categories recorded there. The record does not explain how those safety populations relate to the total enrollment of 50. These distinctions matter because a participant can contribute to one analysis but not another.

In general, a parallel design collects information from distinct groups over the same study period. Without randomization, baseline characteristics or other factors may differ between groups, even when matching is used. Matching can make selected characteristics more comparable, but it does not establish that all relevant characteristics are balanced. The record does not report a randomized treatment comparison or enough details to infer one.

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

Analysis population for the primary outcome, as defined in the registry: Analysis for change in binding potential (binding potential difference; at baseline versus stimulant induced binding potential) was done with 24 cocaine users since one of the subjects only underwent baseline scanning. However, treatment data for all 25 cocaine users was used.

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 Change From Baseline in the Binding Potential of [11C]Raclopride, measured over baseline and 3 months.

The primary endpoint is the change from baseline in the binding potential of [11C]Raclopride, expressed as a ratio, with the timeframe listed as baseline and 3 months. The record describes a comparison involving binding potential under baseline and stimulant-induced conditions. It relates this measure to methylphenidate-induced dopamine release in the striatum, assessed through displacement of [11C]-Raclopride after oral methylphenidate.

The registry explains the biological interpretation of the direction of change: endogenous dopamine release is inversely related to the change in binding potential, described as delta BPND. A negative delta BPND, or increased displacement of [11C]Raclopride, reflects an increase in endogenous dopamine release over the course of treatment. This is the stated interpretation of the measurement, not a reported finding about the participants’ actual change.

In general, a repeated measurement can describe whether a biomarker differs between two time points. A binding-potential measure is used as an imaging indicator related to dopamine release; it is not itself a direct measure of treatment response. The study also examined the relationship between imaging and response to the behavioral treatment. That relationship is a distinct question from whether the mean imaging measure changed over time.

The record gives the endpoint definition and the analysis population but does not report the observed mean change, standard deviation, confidence interval, or test result. It therefore does not establish the size or precision of any change in the primary endpoint. The one participant with baseline scanning only was not included in the stated change analysis, while treatment data for all 25 cocaine users were used.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are easiest to interpret when the question, measurement, population, and analysis are kept distinct. The record describes a continuous primary measure summarized as a mean, with standard deviation as its dispersion measure. It identifies the measure as change in [11C]Raclopride binding potential and gives baseline and 3 months as the timeframe. However, the registry record does not report the numerical mean, standard deviation, or inferential statistics for that endpoint. The methods below explain general concepts relevant to this design; they are not a claim that any unreported method was used.

What does a mean change represent?

In general, a mean change describes the average difference between repeated measurements for participants who contribute the relevant observations. It summarizes the center of the observed changes, but it does not show how changes varied among individuals. The standard deviation describes the spread of observations around the mean. It is not the same as the uncertainty in the estimated mean: uncertainty also depends on how many observations contribute and on the analysis design. The registry’s endpoint description says the change analysis included 24 cocaine users, while treatment data for all 25 cocaine users were used. It does not report the actual mean or standard deviation.

For a repeated-measure endpoint, an analysis may use participant-level changes or a model that accounts for repeated observations. These approaches can address within-person measurements in different ways. The registry record does not identify the specific statistical model, covariates, or variance assumptions used. It would therefore be inappropriate to attribute a particular repeated-measures method to the investigators.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while the interval’s position relative to a relevant reference value helps readers assess which effect sizes remain compatible with the data. It does not mean that the true value has a specified probability of lying in one particular calculated interval. The registry record does not report a confidence interval for the primary endpoint.

A p-value is also an inferential summary, but it does not indicate the size of an effect or the probability that a hypothesis is true. A small p-value can accompany an effect of limited magnitude, and a large p-value can arise when an estimate is imprecise. Effect estimates and uncertainty intervals are therefore important alongside any test result. The registry record does not report a primary endpoint p-value.

Why does the design affect interpretation?

In general, random allocation helps make treatment groups comparable, on average, with respect to both measured and unmeasured baseline factors. This study is listed as non-randomized. Its healthy comparison group was matched for cigarette smoking, gender, and ethnicity, but those characteristics alone do not establish comparability on all other factors. Moreover, healthy controls are not described as a group receiving an alternative treatment. Group differences may therefore reflect differences beyond treatment exposure. A treatment effect cannot be inferred solely from a comparison between these groups.

The study is listed as parallel and unmasked. In general, a parallel design observes distinct groups rather than assigning each participant to multiple treatment conditions. Lack of masking may affect measurement or reporting in some settings, but the registry does not describe whether or how that occurred in this study. No additional procedures for allocation, masking, or outcome assessment are reported in the registry record.

How should the biological measure be read?

The record describes methylphenidate-induced dopamine release in the striatum as measured by displacement of [11C]-Raclopride following oral methylphenidate. It states that endogenous dopamine release is inversely related to the change in binding potential. In practical terms, the registry’s stated direction is that a negative delta BPND, or greater displacement, reflects an increase in endogenous dopamine release over treatment. This biological interpretation specifies what a direction of change would mean; it does not reveal whether the participants showed that direction, since the observed estimate is not reported.

In general, an imaging biomarker is a measured indicator tied to a biological process, not automatically a direct measure of a clinical outcome. A relationship between such a biomarker and treatment response would need an estimate and uncertainty assessment to show how strong and precise the observed association was. The registry states that this relationship was studied but does not report its numerical result or the statistical method used to evaluate it.

What do the planning assumptions describe?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect is described as a stated share of the observed effect. These are planning assumptions, not evidence about the probability that the completed study detected an effect. In general, planning calculations ask what sample size would be needed under specified assumptions; they do not measure observed power after data collection. The registry does not report that these assumptions were the study’s original design justification. The actual sample-size justification is not reported in the registry record.

In general, a planning estimate depends on the outcome variability, target effect, significance level, allocation, and statistical model. If the assumptions do not match the study’s design or data, the resulting illustration may not describe the study’s actual operating characteristics. The record does not report the full inputs or original protocol rationale needed to assess that correspondence. No sample-size illustration should be read as an observed treatment effect or as a substitute for the missing endpoint results.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Cocaine Users", "Control Subjects")
n   <- c(24, 25)
m   <- c(-13.7, -5.8)
sp  <- c(8.7, 8.6)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Cocaine Users  24  -13.700  8.700  -17.374  -10.026
CARM  Control Subjects  25  -5.800  8.600  -9.350  -2.250

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses. It also identifies the primary endpoint and lists secondary outcomes involving cocaine craving, withdrawal symptoms, and pattern of cocaine use. The record does not describe whether the analyses were prespecified in a protocol, whether any multiplicity adjustment was planned, or how findings across outcomes were to be interpreted. A statistical analysis plan is not reported in the registry record.

In general, testing multiple outcomes or multiple relationships can increase the chance of obtaining at least one apparently unusual result by chance. Methods for addressing this include adjusting the testing procedure or defining a hierarchy of primary and secondary questions. Whether such methods are appropriate depends on the study aims and analysis plan. The registry record does not report whether they were used, so no adjustment method should be assumed.

The primary change analysis included 24 cocaine users because one participant underwent baseline scanning only; the record says treatment data for all 25 cocaine users were used. This indicates that the analysis populations differed by outcome or measurement availability. The registry does not report why the follow-up scan was unavailable, whether other data were missing, whether missingness was assessed, or whether imputation or sensitivity analyses were performed. In general, missing repeated measurements can affect both the number of observations and the interpretation of an estimated change. The approach used for missing data is not reported in the registry record.

The record does not describe the full analysis populations for every outcome, any exclusions beyond the stated scan limitation, or whether analyses were adjusted for baseline characteristics. It also does not report interim analyses or a complete statistical plan. These omissions limit assessment of how the posted analyses were selected and how robust they may be to alternative assumptions. The completed status and the listed number of analyses do not resolve those reporting gaps.

12. 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.

The safety record lists 24 cocaine users at risk for serious adverse events and 24 at risk for other adverse events. It records zero affected participants in each of those event categories for that group. For control subjects, it lists 25 at risk for serious adverse events and 25 at risk for other adverse events, with zero affected participants in each category. No serious adverse-event terms are listed.

These figures describe the registry’s recorded counts in the stated groups; they do not establish that no adverse experiences occurred outside the recorded categories or reporting period. The registry lists deaths as null for both groups, so death counts are not reported in the registry record. A null entry should not be interpreted as a recorded count of zero.

In general, safety counts should be read with their denominators and the definition of the event category in view. The counts at risk in the safety record are not identical to the stated total enrollment of 50, and the registry does not explain that difference. The safety figures also do not establish a causal comparison between the groups. The design is non-randomized, and the record does not describe the healthy controls as a treatment control group. These event counts are descriptive registry entries, not evidence by themselves about treatment safety or comparative risk.

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

The record describes a study of imaging measures associated with dopamine release during a behavioral treatment for cocaine dependence. It identifies the primary endpoint, its measurement timeframe, the participant population used for the change analysis, and the intended relationship between imaging and treatment response. It also records a completed study status and lists secondary outcomes. These details clarify what the investigators set out to examine, but they do not supply the numerical outcome estimates needed to determine what the study observed.

The registry states how the direction of the primary measurement relates to endogenous dopamine release: a negative change in binding potential, or increased displacement of [11C]Raclopride, reflects increased dopamine release over the course of treatment. That is an interpretation rule for the endpoint. It does not mean that the participants’ dopamine function recovered, that it changed in a particular direction, or that treatment response was associated with the imaging measure. Those findings are not reported in the registry record.

The record’s design also sets limits on what comparisons can establish. Allocation is non-randomized, and the healthy matched subjects are not described as receiving an alternative treatment. Matching on smoking, gender, and ethnicity does not rule out differences in other characteristics. Therefore, a contrast between cocaine users and healthy controls would not by itself identify the causal effect of the behavioral intervention. The study’s stated interest in response and dopamine function is a research question, not a result.

The primary change analysis used data from 24 cocaine users, while treatment data for all 25 were used. This distinction means that the analysis population depends on the outcome being examined. The registry does not report the observed mean, standard deviation, confidence interval, or p-value for the primary endpoint, nor numerical results for the described relationship with treatment response. Precision and statistical significance therefore cannot be evaluated from the posted record.

In general, a completed study can still have incomplete public reporting of numerical findings. The record supports a description of the design and planned scientific question, but not a conclusion about the size, direction, or certainty of the primary result. It also does not support medical advice or a claim that the treatment does or does not work.

14. Why This Trial Matters Statistically

This study illustrates why an imaging endpoint and a clinical response outcome should be distinguished. The primary measure is a change in [11C]Raclopride binding potential, interpreted in relation to endogenous dopamine release. Treatment response is a separate outcome, assessed using the Community Reinforcement Approach and Contingency Management. A biomarker can be scientifically informative while still requiring a separate analysis to show whether it is associated with a clinical or behavioral response.

The design also demonstrates the importance of identifying the comparator’s role. Healthy matched subjects can offer a point of comparison for selected characteristics or measurements, but they are not automatically a control group for estimating a treatment effect. In this record, allocation is non-randomized, and the healthy comparison subjects are not described as receiving an alternative intervention. Statistical interpretation must follow that design rather than treating all listed groups as interchangeable.

Analysis-population details matter as well. The primary change analysis included 24 cocaine users, while treatment data were used for all 25. Reporting those populations makes clear that the imaging change and treatment analyses do not necessarily use identical data. In general, clear participant accounting helps readers understand what each estimate represents and where missing measurements may affect interpretation.

The registry explains the endpoint’s biological direction but does not report the numerical estimates needed to evaluate the result. This makes the distinction between an outcome definition and an outcome finding especially important. Without an estimate and an uncertainty measure, readers cannot judge the magnitude or precision of the observed change. The record therefore highlights a central statistical principle: study design and endpoint descriptions are necessary for interpretation, but they do not substitute for reported results.

15. 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 interpreting the findings is that numerical primary outcome results are not reported in the registry record. The record does not give the mean change, standard deviation, confidence interval, or p-value, and it does not provide a numerical estimate of the relationship between imaging and treatment response. Consequently, the magnitude, direction, and precision of the primary finding cannot be assessed from the posted information.

The non-randomized design limits causal interpretation. The healthy matched comparison subjects were not described as receiving an alternative treatment, and matching was reported for cigarette smoking, gender, and ethnicity. The record does not state that other factors were balanced or adjusted for. The study therefore cannot be read as a randomized comparison of the behavioral intervention against another treatment.

The imaging change analysis included 24 cocaine users because one participant had only baseline scanning; treatment data for all 25 were used. The reason for the missing scan and the handling of missing data are not reported in the registry record. This leaves uncertainty about whether the unavailable measurement could affect the observed change estimate. The record also does not describe the full analysis populations for all outcomes.

The registry does not report the complete statistical plan, including model specifications, covariate adjustment, multiplicity procedures, or interim analyses. The stated planning assumptions are described as illustrations computed from an observed effect, but the study’s original sample-size justification is not reported. The description of the intervention does not include its schedule or duration. Finally, the safety record lists deaths as null, so deaths are not reported in the registry record rather than recorded as zero. These reporting limits are distinct from evidence that an effect or event was absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence — NCT00376558.
• Registry record last updated 2016-07-01; status last verified 2016-05.
• Results first posted 2016-07-01.
• 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.

19. Record Summary

The registry record describes NCT00376558, a completed, parallel, non-randomized study with no masking, sponsored by New York State Psychiatric Institute. It lists an enrollment of 50 and dates of 2006-07 for study start and 2010-07 for primary completion. The study examined dopamine-related imaging during Contingency Management with the Community Reinforcement Approach for cocaine dependence and included healthy matched comparison subjects.

The primary endpoint was change from baseline in [11C]Raclopride binding potential, with measurements at baseline and 3 months. The change analysis included 24 cocaine users; treatment data for all 25 cocaine users were used. The record lists craving, withdrawal symptoms, and pattern of cocaine use as secondary outcomes.

Numerical primary outcome estimates and the statistical plan are not reported in the registry record. The safety entries record zero serious and other adverse events among the listed participants at risk, while death counts are not reported in the registry record. The design and endpoint description identify the study question, but the posted record does not provide enough numerical outcome information to assess the primary result’s magnitude or precision.