CURE Addiction Center of Excellence: Brain Mechanisms of Relapse and Recovery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CURE Addiction Center of Excellence: Brain Mechanisms of Relapse and Recovery (NCT01587196), a na phase 2 study. The primary outcome is Illicit-positive Urines During Treatment and Follow-up.

2. Clinical Question

3. Trial Design

This completed phase 2 study is registered as a single-group intervention study sponsored by the University of Pennsylvania. The registry lists enrollment as 72 and identifies prescription opiate or medication dependence as the condition. Its title concerns brain mechanisms of relapse and recovery, with an official title specifying prescription opiates or medication. The record lists a start date of 2012-01 and primary completion on 2021-01-01.

The intervention arm is called Naltrexone Intervention, and Vivitrol is listed as the drug intervention. According to the arm description, eligible participants receive up to three monthly injections of 380 mg naltrexone in dissolvable polymer microspheres by deep intramuscular injection. The medication is described as slowly released over approximately 4 weeks. The brief summary describes active medication over 12 weeks and says that participants were to be scanned before, during, and after treatment.

The study summary describes fMRI measures and probes of reward and inhibition as biomarkers to be correlated with drug use during treatment and follow-up. It identifies urine drug screening as the clinical outcome. The primary outcome entry is a participant count associated with illicit-positive urines during treatment and follow-up, with a timeframe of three months. The operational details of the biomarker analyses and the urine-outcome scoring rule are not reported in the registry record.

The record does not describe a randomized comparison: allocation is listed as NA, masking as none, and the model as single group. The registry itself cautions that the arms are not a like-for-like control comparison. There is no separate comparator arm described in the registry record of this record, so outcomes cannot be interpreted as a randomized estimate of naltrexone versus another treatment or no treatment. The registry status is completed, but completion alone does not supply outcome estimates or establish what happened to participants during follow-up.

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: 50 individuals were lost to attrition. 4 individuals withdrew from the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Individuals were tested for presence of opioids: buprenorphine, methadone, opioids, and oxycontin within their urine toxicology

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 Illicit-positive Urines During Treatment and Follow-up, measured over three months.

The primary endpoint is titled “Illicit-positive Urines During Treatment and Follow-up.” Its unit is participants, and its parameter is a count of participants. The description says individuals were tested for buprenorphine, methadone, opioids, and oxycontin in urine toxicology. The timeframe is listed as three months. Urine testing is an objective way to assess the presence of specified substances at the time of specimen collection, and such measures can be used to characterize drug use during a treatment period and follow-up.

The participant-count formulation matters: it is not the same as reporting the total number of positive urine specimens, the proportion of tests that were positive, or the number of positive results per participant. The registry record does not specify whether a participant was counted after any positive test, how repeated tests were handled, how missing or invalid specimens were treated, or how the listed substances contributed to the outcome. Those definitions are important for reproducing the endpoint and interpreting its clinical meaning.

No observed primary outcome count, group denominator for the endpoint, effect estimate, or uncertainty interval is reported in the registry record. The record therefore identifies what was intended to be measured but does not provide the posted result needed to quantify the observed urine outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint count?

The primary outcome is expressed as a count of participants with an event, not as a continuous measurement. For a binary outcome, each participant is classified according to whether the endpoint definition is met, and the result can be described by the number meeting that definition and the number assessed. The registry identifies the relevant event through illicit-positive urine testing, but it does not state the classification rule. In particular, it does not say whether any positive specimen is sufficient, whether a pattern of results is required, or how multiple specimens are condensed into a participant-level classification.

This distinction is more than a matter of wording. A participant-level count can be useful for a straightforward summary, while a specimen-level analysis can incorporate repeated observations and address the frequency or timing of positive tests. Those analyses answer different questions and may require different methods. The posted record does not provide the repeated-test schedule, the participant-level outcome rule, or an analysis of specimen-level results, so such details should not be inferred.

What does a single-group design allow?

In a single-group study, results describe the participants who received the study intervention. A summary of outcomes can show what was observed in that group, but there is no concurrent control group in this record to provide the comparison needed for a randomized treatment-effect estimate. Even a change from a participant’s earlier measurement can reflect time, other care, or changes in circumstances as well as the intervention. General statistical interpretation therefore distinguishes a within-group observation from a causal comparison between treatment strategies.

Here, the registry lists allocation as NA, masking as none, and a single-group model. Its note explicitly says the arms are not a like-for-like control comparison. The record does not report a separate comparator, random assignment, or a blinded outcome assessment. These design features limit what an outcome difference, if reported, could establish. They do not make descriptive reporting uninformative, but they do mean it should not be described as a randomized comparison.

How should precision be assessed?

A confidence interval is a statistical range that conveys uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval compatible with a range of materially different values signals uncertainty about the size of the underlying effect. A p-value, when reported, addresses compatibility of data with a specified null model; it does not describe the magnitude or clinical importance of an estimate. These are general statistical concepts, not results reported for this study.

The registry does not provide an estimate, confidence interval, or p-value for the primary endpoint. Its analysis count is zero. Thus, precision cannot be evaluated from a reported inferential result. A count alone, if one were available, would also need its denominator and a clear endpoint definition to be interpreted. Neither a denominator for the primary endpoint nor an uncertainty measure is reported in the registry record.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are assumptions for an illustrative sample-size calculation, not evidence that the trial used those assumptions to set its enrollment. The registry record does not report the trial’s own sample-size justification or design calculation.

Planning calculations of this kind explore how a future study’s size might relate to a chosen effect and analysis assumptions. They are not observed power, and they do not repair the absence of a posted treatment-effect estimate. The described equal-allocation, two-arm assumption also differs from the registered single-group design, so it should not be read as a description of the enrolled study. No resulting sample-size figures are reported in the registry record.

The general point about over-dispersion is that data can vary more than a chosen statistical model expects, which can make standard errors too small if the model does not account for that extra variation. This is especially relevant to some count-data models. The primary endpoint is described as a participant count for a binary event, not as a reported rate of repeated urine specimens. The registry does not report a fitted model, distributional diagnostics, or an over-dispersion assessment, so no conclusion about whether such a correction was needed can be drawn.

What is not available for recalculation?

A simple unadjusted recalculation requires posted summary statistics appropriate to the comparison, such as event counts and denominators for each group. This record does not report primary endpoint counts or a separate comparator group, and it lists no analyses. Accordingly, an unadjusted effect estimate or its uncertainty cannot be recalculated from the registry information. There is also no reported sponsor analysis to compare with a recalculation. The absence of a recalculation is not evidence for either a null effect or a particular direction of effect; it reflects that the necessary result data are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, time points, biomarkers, or statistical contrasts. Testing many questions can increase the chance of a seemingly notable result arising by chance, so interpretation depends on knowing which analyses were planned as primary, how secondary analyses were handled, and whether any adjustment or hierarchy was used. The registry identifies one primary outcome measure and describes fMRI biomarkers as part of the study’s aims, but it does not report a multiplicity strategy, a full analysis plan, or final biomarker analysis results. The handling of multiple comparisons is not reported in the registry record.

Missing-data methods are also important for urine-based outcomes. Participants may have missing specimens or incomplete follow-up, and the way those observations are classified can influence a participant-level endpoint. The registry does not report the number of expected or collected urine specimens, the extent of missingness, reasons for missing data, or an imputation or sensitivity-analysis approach. It also does not specify how missing or invalid specimens affected the primary endpoint.

The record lists enrollment as 72, but it does not report the number included in the primary outcome analysis or define an analysis population. It is therefore not possible to tell from the registry record whether the analysis included all enrolled participants, only those receiving intervention, participants with sufficient urine data, or another subset. The participant-flow details and analysis-population definitions are not reported.

Zero analyses are listed in the registry. As a result, there is no reported account of adjusted or unadjusted analyses, covariate selection, handling of repeated measurements, or sensitivity checks. Such information should not be inferred from the study’s stated aims or design description.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry’s safety entries list the Naltrexone Intervention group with 72 at risk for serious adverse events and zero affected. For other adverse events, it also lists 72 at risk and zero affected. Deaths are listed as zero. These are the counts recorded for the group; they are not estimates from a comparison with a control group.

A recorded zero means that no events in that category are represented in the posted count. It does not establish that an event is impossible, that every potential event was detected, or that all relevant safety information is complete. Interpretation depends on the event definitions, collection procedures, follow-up coverage, and completeness of reporting. Those details are not reported in the registry record. The record also gives no serious-event terms in its list of top serious terms.

The at-risk entries should be read as the registry’s reported denominators for the safety categories, not as proof that every participant had identical exposure or follow-up. The intervention description allows up to three monthly injections, but actual treatment received is not reported. These entries therefore describe the posted safety counts, not a comprehensive account of exposure or a comparative safety assessment.

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

The record establishes that a completed phase 2, single-group study of naltrexone was registered for people with prescription opiate or medication dependence. It identifies urine toxicology for specified substances as the basis of the primary outcome and describes a three-month timeframe. It also records the intervention details and lists zero serious adverse events, zero other adverse events, and zero deaths in the intervention group.

It does not establish the frequency of illicit-positive urine outcomes, because the participant count for that endpoint is not reported. Nor does it provide an effect estimate, confidence interval, or p-value for the primary outcome. The study summary describes an intended relationship between fMRI measures and drug use, but the registry does not report results for that relationship. The stated research aim should not be mistaken for a demonstrated biomarker finding.

The single-group design has a further implication. Without a separate comparator, an outcome observed during treatment and follow-up cannot by itself show what would have happened under another treatment or without the intervention. The record does not describe random allocation or masking, and it explicitly warns against treating arms as a like-for-like control comparison. Any causal claim about comparative benefit or harm would go beyond the information reported.

Some important endpoint and analysis details are also absent, including the participant-level rule for classifying positive urine tests, missing-data handling, the analyzed population, and the statistical analysis plan. Those omissions limit reproducibility and make it difficult to assess the robustness or precision of any potential finding.

Accordingly, the appropriate reading is descriptive and bounded: the registry identifies what the investigators intended to study and records safety counts, but it does not report the primary clinical outcome result or the analyses needed to quantify it. The absence of a posted result does not demonstrate that the intervention had no effect, just as the study’s stated rationale does not demonstrate that it had an effect.

13. Why This Trial Matters Statistically

This study is statistically notable for the gap between a clearly stated biomarker-and-clinical-outcome aim and the limited result information in its registry record. The summary describes fMRI measures, probes of reward and inhibition, and urine drug screening, with a proposed correlation between brain measures and drug use. Those aims raise questions about measurement timing, repeated observations, endpoint definition, and analysis of associations. The record does not report the results or analytic details needed to answer those questions.

The participant-level binary endpoint also illustrates why operational definitions matter. A urine test is collected at a particular time, while a count of participants requires a rule for combining test results across the timeframe. Without that rule, readers cannot know precisely what a participant counted as having an illicit-positive urine result represents. Clear reporting of the number assessed, the number meeting the definition, and the handling of missing specimens would make the outcome more interpretable.

Design structure is equally important. A single-group study can describe participants’ outcomes, but it cannot supply the same comparative evidence as a randomized, controlled design. The registry’s own note cautions that the arms are not a like-for-like control comparison. Recognizing that limitation prevents a descriptive pattern from being overread as a treatment effect.

Finally, the record’s planning illustration is distinct from the registered design and from observed evidence. It uses assumptions for a two-arm calculation, while the study is registered as single group. Keeping planning assumptions separate from enrollment decisions, observed outcomes, and inferential results is essential for sound statistical interpretation. The record’s missing outcome and analysis details make transparent reporting especially important.

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 trial from its registry record is that the primary endpoint is named but its observed result is not reported. There is no participant count meeting the endpoint, no endpoint denominator, and no effect estimate or uncertainty interval. The record lists zero analyses, so the magnitude and precision of the primary outcome cannot be assessed.

The outcome definition is incomplete for independent interpretation. The entry says participants were tested for buprenorphine, methadone, opioids, and oxycontin, but does not state how many urine collections were planned or how multiple results were combined into a participant count. Whether a participant needed any positive result or another pattern is not reported. Nor are missing, invalid, or refused tests addressed.

The single-group design means the record does not provide a randomized control comparison. Allocation is listed as NA, masking as none, and the registry cautions that arms are not a like-for-like control comparison. Therefore, even if within-group outcome changes were reported, they would not alone distinguish intervention effects from other changes over time or concurrent influences.

Other design and analysis details are absent, including eligibility criteria, baseline characteristics, actual intervention exposure, participant flow, analysis-population definitions, multiplicity handling, and the statistical analysis plan. The stated biomarker aims are not accompanied by reported association estimates. The safety record lists zero events in its categories but does not report event definitions, ascertainment procedures, or follow-up completeness. These gaps constrain reproducibility and prevent a comprehensive assessment of clinical outcomes, statistical uncertainty, or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CURE Addiction Center of Excellence: Brain Mechanisms of Relapse and Recovery — NCT01587196.
• Registry record last updated 2024-10-15; status last verified 2024-10.
• Results first posted 2024-10-15.
• 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

NCT01587196 is a completed phase 2, single-group study sponsored by the University of Pennsylvania. It concerns prescription opiate or medication dependence and lists enrollment as 72. The intervention is naltrexone, identified as Vivitrol, with an arm description of up to three monthly injections containing 380 mg. The study summary describes 12 weeks of active medication and fMRI scanning before, during, and after treatment.

The primary endpoint is titled “Illicit-positive Urines During Treatment and Follow-up,” is a participant count, and has a three-month timeframe. The registry does not report the endpoint count, its analysis, or the biomarker findings. Allocation is listed as NA, masking as none, and the study model as single group. Safety entries list zero serious adverse events, zero other adverse events, and zero deaths in the intervention group. The registry record does not provide enough outcome or analysis detail to quantify the primary clinical result or its precision.