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 Imaging the Neurochemistry of Drug Addiction With PET (NCT02817698), a na early/phase 1 study. The primary outcome is Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02817698 |
| Phase | EARLY/Phase 1 |
| Condition | Smoking, Cannabis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
Population
People described in the registry as dependent on nicotine, cannabis, or cocaine. The record does not report further eligibility details or participant characteristics.
Intervention
Administration of each participant’s drug of dependence: tobacco cigarettes for nicotine-dependent subjects, cannabis cigarettes for cannabis-dependent subjects, and IV cocaine for cocaine-dependent subjects. Cannabis is the intervention listed in the registry.
Comparator
There is one study arm, with baseline imaging before drug administration and follow-up imaging after administration. The record does not describe a separate control arm.
Primary question
How does dopamine-related PET binding potential change from baseline after administration of the drug of dependence?
The study’s broad objectives were to use PET technology to investigate dopaminergic neurochemistry associated with marijuana, traditional cigarettes, and cocaine, and to extend PET to the opioid-ergic system using those drugs. The primary endpoint focuses on change in dopamine levels as inferred from change in raclopride binding potential. Baseline PET was conducted after overnight abstinence, followed by drug administration and a second PET acquisition. This is a within-person before-and-after question, not a randomized comparison of treatment groups. The registry record does not report the observed change, so it cannot establish the direction or size of any imaging response. It also does not report an endpoint result for each drug group separately.
3. Trial Design
This is an early-phase, single-group study with allocation listed as not applicable and masking listed as none. The registry describes one arm, in which subjects receive their drug of dependence. Nicotine-dependent subjects receive tobacco cigarettes, cannabis-dependent subjects receive cannabis cigarettes, and cocaine-dependent subjects receive IV cocaine. The intervention listing names cannabis. These descriptions indicate the study’s planned scope, but the record does not provide enrollment or outcome counts separated by drug-dependence group.
The registry records enrollment of 25 and a completed status. The recorded start date is 2017-11-29, and the primary completion date is 2022-01-12. Completion is a trial-status designation; it does not establish that results were posted. The record describes two overarching goals: investigating dopaminergic neurochemistry with PET and extending PET to the opioid-ergic system. It does not report how those goals were divided into analytic cohorts or whether every goal was addressed in the posted outcomes.
The primary endpoint uses a baseline scan and a scan after drug administration. Baseline imaging followed overnight abstinence. The drug was scheduled 35 minutes before the second 90-minute PET acquisition. The second scan was expected to begin approximately 5 hours after the first scan began, although the record notes that timing could be longer or that scans could occur on separate days because of scheduling constraints or cancellations. Since there is no separate control arm, changes over time cannot be separated from other time-related influences by a randomized control comparison. The registry record does not report a sample-size justification, a detailed statistical analysis plan, or specific methods for handling scan timing variation.
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 | Drug of Dependence |
|---|---|
| STARTED | 25 |
| COMPLETED | 25 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Subjects were analyzed based on cluster size with a threshold of 16 voxels.
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 | Drug of Dependence |
|---|---|---|
| Participants analysed | 25 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 25 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 29.52 (19 to 49) |
| Sex: Female, Male: Female | Participants | 11 |
| Sex: Female, Male: Male | Participants | 14 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 9 |
| Race (NIH/OMB): White | Participants | 14 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 25 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Dopamine Levels at Baseline and After Drug of Dependence Administration as Confirmed by PET Images., measured over 90 minute PET scan acquisition. Drug of dependence will be given at -35 mins.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | mm^3 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is described as change in dopamine levels at baseline and after administration of the drug of dependence, confirmed by PET images. The registry operationalizes this change through change in raclopride binding potential. Its stated parameter is a mean, its stated dispersion is the full range, and the unit is mm^3. The record describes PET images at baseline and after drug administration rather than a comparison between separate randomized arms.
Baseline levels were assessed in the first morning scan after overnight abstinence, using a 90-minute PET acquisition. The drug was administered 35 minutes before the second 90-minute acquisition. The registry describes the second scan as beginning approximately 5 hours after the first scan began in typical scheduling, while also allowing for longer intervals or scans on separate days.
Using a defined imaging measure gives the study a way to express neurochemical change through PET rather than relying only on a clinical description. In general, a binding-potential measure is an imaging-derived indicator, not a direct measurement of dopamine concentration. The registry record does not explain the biological calibration of the measure, its expected direction, or a clinically meaningful threshold for change. It also does not report the observed endpoint value or its uncertainty.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a planned within-person imaging assessment: PET at baseline after overnight abstinence, followed by drug administration and a second PET acquisition. The primary outcome is defined as a mean change in raclopride binding potential, with the registry identifying dopamine levels as the biological quantity of interest. However, no primary endpoint result is reported in the registry record. The record also lists zero analyses. There is therefore no posted estimate of change, no measure of precision, and no statistical test result to interpret.
This absence matters because a study description and a result answer different questions. The design tells readers what investigators intended to measure and when. It does not show whether the measure increased, decreased, or remained similar after administration. Nor does a completed status supply the missing outcome estimate. The enrollment figure describes the registered study enrollment, not the number of participants with usable PET data or the number contributing to a particular analysis; those counts are not reported in the registry record.
The single-group structure also shapes what any eventual before-and-after result could mean. In general, repeated observations on the same person can control for stable characteristics of that person, but an uncontrolled before-and-after comparison cannot by itself distinguish the drug-associated change from other changes over time, scan conditions, or measurement variability. This is a general limitation of the design, not evidence that any particular alternative explanation occurred in this study. The registry does not report a separate control group or a randomized comparison.
The endpoint description specifies a mean and a full range, but no mean, range, confidence interval, or other uncertainty estimate is posted. A confidence interval, in general, expresses a range of estimates compatible with the data under a statistical procedure; without a reported estimate and interval, precision cannot be assessed. The record also does not report results by nicotine, cannabis, or cocaine dependence, so the overall description cannot be interpreted as evidence of a response in any one of those groups.
The posted safety figures record no serious adverse events, one other adverse event, and no deaths in the drug-of-dependence group. Those counts are safety reporting, not a substitute for the missing imaging outcome. They also do not establish the comparative safety of drug administration, because the study has no separate control arm and the record does not provide event descriptions for the non-serious event. Overall, the record supports an account of the study question and design, but not a conclusion about the magnitude, direction, precision, or clinical importance of the primary imaging change.
9. Statistical Methods Explained
The registry describes a mean-based endpoint derived from PET images, with change in dopamine levels determined by change in raclopride binding potential. It says images were assessed based on cluster size with a threshold of 16 voxels. The record does not provide the statistical procedures used to estimate the mean change, quantify uncertainty, or test a hypothesis. The concepts below explain how such study features are commonly understood; they should not be read as a claim about an unreported analysis conducted in this trial.
What does a within-person baseline comparison represent?
Each participant’s imaging is described at baseline and after administration. In general, a within-person analysis compares measurements from the same participant at different times. It can account for stable participant characteristics because each person contributes their own baseline reference. The two observations are not independent: their relationship is part of the design and should be reflected in an appropriate analysis. The registry does not identify the method used to account for that relationship, or whether all participants had both scans available for analysis.
A before-and-after contrast is not equivalent to a randomized control comparison. In general, changes between measurement times can reflect the intervention as well as time, measurement conditions, or other influences. A control group can help assess some of these possibilities, but the registry describes a single arm. The record does not report a control condition or a method for adjusting for factors that may vary between scans.
What do the endpoint summary terms mean?
The registry identifies the parameter as a mean. A mean describes the arithmetic average of measurements in an analyzed set; it does not show how much individual measurements differ from that average. The stated dispersion is the full range, which describes the lowest and highest values in the analyzed set. A range is sensitive to extreme observations and does not, by itself, communicate the precision of the mean. No numerical mean, range, standard error, or confidence interval is reported in the registry record.
In general, a confidence interval combines an estimate with its sampling uncertainty. A narrow interval indicates greater precision under the assumptions of the method; a wide interval indicates less precision. It does not establish that a result is clinically important, nor does it correct design limitations. Because the registry provides no outcome estimate or interval, readers cannot judge precision for the primary endpoint from the record.
What does the image threshold indicate?
The population description says subjects were analyzed based on cluster size with a threshold of 16 voxels. A voxel is a unit of image volume, and a cluster-size criterion generally concerns the extent of connected image locations meeting an analysis criterion. The registry does not explain how clusters were formed, what image-level threshold was used before applying the cluster-size criterion, or how the threshold was selected. It also does not report how the criterion affected the number of participants or observations included. The endpoint’s stated unit is mm^3; the record does not explain the relationship between that unit and the voxel-based analysis description.
How should planning calculations be understood?
The registry describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s one-arm design. Any resulting sample-size figures are illustrations for hypothetical planning, not the number enrolled in this study and not observed power. Observed power is not a substitute for an estimate and its uncertainty. The registry record does not provide the endpoint effect value needed to interpret such illustrations, and no calculated sample-size figures are reported in the record.
More generally, planning calculations depend on assumptions about the effect to detect, variability, significance level, allocation, and analysis model. Changing those assumptions changes the planning result. Here, the stated equal-allocation, two-arm setup differs from the registered single-group design, so those planning assumptions should not be read as the trial’s own design rationale. The registry does not report a sample-size justification for the study’s enrollment.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures and zero analyses. It describes one primary endpoint in detail: change in dopamine levels, assessed through change in raclopride binding potential. The information available does not describe the other outcome measure, its timing, or whether it was treated as primary or secondary. No outcome analysis is reported in the registry record.
Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, the more opportunities there are to identify a result, the more important it is to define in advance which analyses are primary and how multiple testing will be handled. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a prespecified testing strategy. It is therefore not possible to determine how multiple outcome measures or any other analyses were intended to be interpreted.
Missing-data procedures and analysis populations are also not reported in the registry record. The primary endpoint description says subjects were analyzed based on cluster size with a threshold of 16 voxels, but it does not say how missing scans, incomplete scan pairs, unusable images, or other exclusions were handled. The enrollment figure does not establish how many participants contributed paired scans or endpoint data. The record also does not specify whether the analysis included all enrolled participants, only those with both scans, or another defined population.
These omissions limit assessment of both representativeness and uncertainty. In general, excluding participants with incomplete or unusable measurements can affect an estimate if the reasons for missingness relate to the outcome. That is a general concern, not a finding about this study. Without counts, reasons, and analysis rules, the extent or direction of any such effect cannot be assessed.
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 |
|---|---|---|---|
| Drug of Dependence | 0 | 25 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Drug of Dependence | 0 of 25 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 4% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Drug of Dependence | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Drug of Dependence |
|---|---|---|
| Anxiety/Tachycardia | General disorders | 1 of 25 |
The registry reports safety figures for the Drug of Dependence group. It records 0 serious adverse events among 25 at risk, 1 other adverse event among 25 at risk, and 0 deaths. The serious-event terms list is empty. These are the posted counts; the record does not provide a description of the other adverse event in the information available.
These figures are counts within the registered group, not a comparison between treatment arms. The study is described as single-group and has no separate control arm, so the safety figures cannot establish how event occurrence compares with a control condition. A count of zero serious events in this group also does not prove that serious events are impossible or that no event was missed. The registry record does not describe how events were collected, assessed, or attributed, or provide further detail about follow-up for safety reporting.
The at-risk counts are reported as 25 for both serious and other adverse events. Those counts should be read as the registry’s safety denominators, not as evidence that every enrolled participant completed every scan or contributed to the primary endpoint. Safety reporting and the imaging outcome answer different questions; the adverse-event counts do not indicate the direction or precision of any change in raclopride binding potential.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed, early-phase PET study with a single-group before-and-after design. It describes a primary imaging question about change in raclopride binding potential following administration of the drug of dependence. It also records enrollment of 25 and provides a limited safety summary. These details help readers understand what the investigators intended to examine and the broad structure of the study.
The record does not provide the observed primary endpoint result. It therefore does not show whether dopamine-related binding potential changed, how large any change was, how variable it was, or how precisely it was estimated. There is no reported confidence interval or statistical test result to support a judgment about the strength of evidence. The registry’s completed status does not fill that gap.
Even if a before-and-after estimate were available, the design would not provide the same causal evidence as a randomized comparison with a control group. General changes over time, scan timing, or measurement variability could contribute to a difference between baseline and post-administration measurements. The registry record does not report a method for separating such influences from drug-associated change.
The study’s broad goals refer to dopaminergic neurochemistry and extension to the opioid-ergic system across drugs of abuse. The detailed primary endpoint, however, concerns dopamine-related change measured through raclopride binding potential. The record does not report results for the opioid-ergic goal, nor does it provide separate endpoint results for nicotine-, cannabis-, or cocaine-dependent subjects. Conclusions about those individual groups or about the broader goals are therefore not supported by the posted endpoint information.
The safety figures describe reported events in the study group, but do not establish comparative safety. Overall, the registry supports a description of the trial’s question, imaging schedule, and design, not a conclusion that the intervention produced a particular neurochemical effect or that such an effect was clinically meaningful.
13. Why This Trial Matters Statistically
This study illustrates why imaging endpoints need to be read in the context of their measurement process. The primary question is framed as dopamine change, but the registry describes the endpoint as change in raclopride binding potential. That operational definition matters: the measured imaging quantity is the basis for the stated biological interpretation, and the record does not report a direct dopamine concentration or a calibration linking the imaging measure to a clinically meaningful threshold.
The baseline and post-administration scans also make timing part of the endpoint. Baseline imaging followed overnight abstinence, and the second scan followed drug administration, with the record allowing scheduling differences that could include separate days. In general, timing and scan conditions can influence how a repeated-measures result is interpreted. The registry does not report a statistical approach to account for such variation, so readers cannot assess its impact on an estimate.
The study is also a useful example of the difference between a study being complete and its results being available. The registry lists a completed status and an enrollment figure, while reporting zero analyses and no primary endpoint estimate. Without estimates and uncertainty, the central statistical question remains unanswered in the registry record. A design description cannot substitute for the outcome data needed to assess magnitude and precision.
Finally, the planning assumptions described for hypothetical two-arm sample-size illustrations do not match the study’s single-group structure. Recognizing that distinction prevents planning calculations from being mistaken for trial design or evidence of power. The record offers a setting in which to separate design, measurement, planning, outcome estimation, and safety reporting rather than treating them as interchangeable forms of evidence.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpretation is that the registry record does not report the primary endpoint result, despite describing the endpoint and marking the study completed. It also lists zero analyses. Without an estimate, a measure of variability, or an uncertainty interval, the direction, size, and precision of the imaging change cannot be assessed.
The single-group design has no separate control arm, and allocation is listed as not applicable. As a result, the design does not support a randomized between-group comparison. Any change between baseline and post-administration imaging would need to be interpreted in light of time and measurement conditions as well as drug administration. The record does not report an analysis intended to distinguish these influences.
The imaging schedule allows some variation. The second scan was expected to begin approximately 5 hours after the first scan began, but could occur later or on a separate day because of scheduling constraints or cancellations. The registry does not report how many scans followed each schedule or how timing differences were addressed statistically.
The record does not give participant characteristics, detailed eligibility criteria, outcome counts by drug-dependence group, scan completion counts, missing-data reasons, or the analysis population beyond the cluster-size description. The intervention listing names cannabis, while the arm description also refers to tobacco cigarettes and IV cocaine for other dependence groups; the record does not report how enrollment or results were distributed across those groups. These gaps limit assessment of who contributed to the endpoint and how broadly any findings would apply.
Finally, the registry does not report a detailed statistical plan, multiplicity handling, or the rationale for the image cluster-size threshold of 16 voxels. These limitations concern what can be evaluated from the registry record; they do not establish that a particular procedure was or was not used outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Imaging the Neurochemistry of Drug Addiction With PET — NCT02817698.
- Registry record last updated 2024-12-12; status last verified 2024-11.
- Results first posted 2024-12-12.
- 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
NCT02817698, titled Imaging the Neurochemistry of Drug Addiction With PET, is recorded as an early-phase, completed, single-group study sponsored by Yale University. The registry lists enrollment of 25, no masking, and no applicable allocation. Its arm description says participants received their drug of dependence, while the intervention listing names cannabis.
The primary endpoint concerns baseline-to-post-administration change in dopamine-related PET imaging, operationalized through raclopride binding potential. Baseline imaging followed overnight abstinence; drug administration was scheduled 35 minutes before the second 90-minute PET acquisition. The registry record does not report a primary endpoint estimate or statistical analysis. It reports 0 serious adverse events, 1 other adverse event, and 0 deaths in the drug-of-dependence group. Consequently, the record describes the study’s purpose and design but does not provide enough outcome information to assess the magnitude or precision of the primary imaging change.