CoMBAT Opioid Use Disorder: A Combined Medication and Behavioral Activation Treatment for People Living With Opioid Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CoMBAT Opioid Use Disorder: A Combined Medication and Behavioral Activation Treatment for People Living With Opioid Use Disorder (NCT04240093), a randomized na study. The primary outcome is Number of Missed Medication Doses - Past 30 Days.

2. Clinical Question

This is a question about a combined care approach, not behavioral activation in isolation: the intervention differed from standard of care by including behavioral activation, while both arms included medication and substance abuse and health navigation counseling. The registry describes random allocation in a parallel-group trial. Its brief summary says participants were randomized 1:1 and followed for 6 months after randomization, with assessments at months 3 and 6.

The primary outcome is a count of missed doses over a stated recall period. It can describe medication-taking behavior as reported by participants, but it is not itself a direct measure of every aspect of treatment engagement or opioid use. Fentanyl and opiate-positive urine toxicology screening is listed among the secondary outcomes. Numerical results for the primary outcome are not reported in the registry record, so the direction and precision of any observed group contrast cannot be described from this record.

3. Trial Design

CoMBAT Opioid Use Disorder was a pilot randomized controlled trial with a parallel-group design and no masking. The registry records the study as completed and lists Brown University as sponsor. Enrollment was 44. The record lists the study start as 2019-11-15 and primary completion as 2022-02-18.

The intervention arm received behavioral activation counseling in addition to substance abuse and health navigation counseling and medication for opioid use disorder. The standard-of-care arm received the counseling and medication without the added behavioral activation component. The brief summary describes 2 sessions of navigation counseling in each arm and 8 behavioral activation sessions in the CoMBAT arm. These descriptions define the intended contrast; the registry record does not give participant-level adherence to the sessions.

Follow-up was planned through 6 months post-randomization, with assessments at months 3 and 6. The primary outcome description also includes baseline measurement. The primary endpoint was self-reported missed methadone or buprenorphine doses in the past 30 days. The registry lists 3 outcome measures and 3 analyses, but the numerical primary outcome summaries and detailed analysis procedures are not reported in the registry record.

Random allocation helps guard against systematic baseline differences on average, but a pilot trial with limited enrollment can still have imbalances by chance. No masking means participants and study personnel were not blinded, according to the registry. That feature matters particularly when an outcome depends on participant report or when an intervention involves counseling: expectations or awareness of treatment assignment could influence reporting or other study processes. This is a design consideration, not evidence that such influence occurred.

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: A total of 44 individuals consented; of these, 12 individuals were lost to follow-up prior to randomization, resulting in a randomized sample of 32 participants (16 CoMBAT experimental arm; 16 Standard of Care control arm).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to Treat Analysis. For the unadjusted means by time-point data, there were missing data for 2 participants in the CoMBAT experimental arm at the 3-month follow-up visit.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Baseline data are reported for all enrolled and randomized participants (n=32).

6. Primary Endpoint

The registry lists the primary outcome as Number of Missed Medication Doses - Past 30 Days, measured over Baseline, 3 month follow-up, and 6 month follow-up.

The primary endpoint is the number of methadone or buprenorphine doses a participant reported missing during the past 30 days. The registry identifies it as a mean with standard deviation and describes raw, unadjusted means at 6-month follow-up. It also lists measurements at baseline and at 3-month follow-up.

A missed-dose count is a direct, understandable measure of medication-taking behavior over a defined recall period. It is relevant to a trial focused on engagement in care and medication treatment. Because the measure is self-reported, it reflects what participants recall and report; it is not equivalent to a medication dispensing record or an independently verified count. The registry record does not report how recall was validated.

As a continuous count, the endpoint can be summarized with a mean and standard deviation. The mean describes the group’s average reported count, while the standard deviation describes how spread out individual reports are around that average. Neither statistic alone describes the full distribution. For example, a small number of higher counts can affect a mean, and the standard deviation does not show whether the distribution is symmetric.

The record gives no numerical means or standard deviations for the primary outcome, and no numerical group contrast or confidence interval is reported in the registry record. Therefore, the endpoint’s observed values, between-arm difference, and precision cannot be interpreted from the information recorded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help connect the design to the questions the trial can answer. The registry identifies random allocation, a parallel-group model, a continuous primary outcome summarized by a mean and standard deviation, and raw unadjusted means at 6-month follow-up. It does not report a detailed statistical analysis plan, the exact model used for repeated measurements, or the method used to calculate uncertainty for an arm contrast. The concepts below are general explanations, not claims that a particular unreported procedure was used.

What does random allocation contribute?

In a randomized trial, assignment is generated by chance rather than chosen by a participant or investigator. This can reduce systematic differences between arms and supports a comparison of assigned treatment strategies. Randomization does not guarantee that the groups will be identical at baseline, especially in a pilot study. Differences can remain by chance, and the registry record does not provide baseline outcome values or covariate summaries for assessing them.

The stated comparison is between a combined intervention and standard of care. Both arms included medication and substance abuse and health navigation counseling; behavioral activation was included in the experimental arm. Thus, any arm contrast would address the added package as assigned, rather than isolate the effect of each component separately.

What does a mean and standard deviation describe?

For a continuous measure, the mean is the arithmetic average of observed values. The standard deviation describes how dispersed those values are around the mean. Together, they give a compact summary, but they do not show every feature of the data. A count of missed doses is bounded and may be skewed, with many low values and fewer higher values. Whether that pattern occurred in this trial is not reported in the registry record.

A mean difference between randomized arms would describe the difference in average reported missed doses. It would not show how every participant responded, and it would not establish that the same difference applies to other populations or care settings. The registry record does not include the numerical means needed to interpret such a contrast.

Why does uncertainty matter?

An estimate from a trial is subject to sampling variability. A confidence interval communicates uncertainty around an estimate under the analysis assumptions. General statistical interpretation considers both the estimated effect and the interval’s range: an estimate can be imprecise even when it points in a particular direction. A p-value, when reported, assesses how compatible the data are with a specified null model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. No primary-outcome confidence interval or p-value is reported in the registry record.

The planning illustration uses a two-sided significance level of 0.05 and a normal approximation. Those assumptions pertain to the planning illustration, not necessarily to the analysis conducted for the trial. The record does not report the trial’s full statistical plan, including whether adjusted analyses, repeated-measures methods, or a particular variance estimator were used.

Why can count outcomes need care?

General methods for count outcomes may account for skewness, a concentration of zero counts, or variability larger than a simple model expects. Over-dispersion means that observed variation exceeds what a chosen model assumes; ignoring it can make standard errors too small and uncertainty appear less than it is. These are general considerations for count data. The registry record does not report a distributional assessment or state whether a count-specific model was used. The primary outcome is summarized as a mean and standard deviation, but that does not establish how the underlying analysis handled its distribution.

What does the planning illustration mean?

The registry describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% power or other stated power targets. These are planning scenarios, not the number of participants who were observed and not observed power. They depend on assumptions about the effect and variability, and they do not prove that a future study would attain the planned power.

The registry record does not provide a sample-size justification for the original trial. Nor does it report interim analyses or stopping rules. Those items should not be inferred from the planning illustration. Numerical planning results are not included in the record details available for this interpretation, so no sample-size figure can be described.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 3 analyses. It does not report a multiplicity adjustment, a hierarchy of confirmatory hypotheses, or a detailed statistical analysis plan. When a study evaluates several outcomes or time points, multiple statistical tests can increase the chance of at least one apparently notable result by chance. General approaches include prespecifying a primary comparison, adjusting for multiple testing, or treating findings as exploratory. The registry record does not say which approach, if any, governed the reported analyses.

The primary outcome is listed at baseline, 3-month follow-up, and 6-month follow-up. Its description specifies raw, unadjusted means at 6-month follow-up, while also describing change over time. The registry does not identify a single numerical primary comparison in the registry record for interpretation. The primary outcome has several categories or time points and is not reduced to one comparison in the posted information. Therefore, a particular time-point contrast or change estimate should not be assumed.

The record states that unadjusted means by time point had missing data for 2 participants in the CoMBAT experimental arm at the 3-month follow-up visit. It does not report the missing-data handling method, reasons for missingness, or whether other analyses used different analysis sets. Missingness can affect interpretation if the likelihood of having an observed outcome is related to the unobserved outcome. General methods may include complete-case analysis, imputation, or models using available repeated measurements, but none should be attributed to this trial without documentation.

The primary outcome description names an intent-to-treat analysis. That label indicates an analysis framed around randomized assignment, but the record does not provide enough detail to determine precisely how missing values or deviations from assigned treatment were handled. Numerical results by analysis population are not reported in the registry record.

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 reports 0 serious adverse events among 16 participants at risk in the experimental arm and 0 among 16 participants at risk in the standard-of-care arm. It also reports 0 other adverse events among 16 at risk in each arm, and 0 deaths in each arm. These are the safety figures recorded for the groups.

A zero count means that no events of the specified category were recorded among the stated at-risk group in the registry record. It does not demonstrate that the underlying risk is zero. With no events recorded, the data cannot precisely establish how frequently an event might occur outside the observed participants, and the registry figures alone do not provide a risk estimate with an uncertainty interval.

The safety denominators are reported separately from the overall enrollment figure. The registry does not explain the relationship between those denominators and enrollment, or provide further detail about safety surveillance, event definitions, or duration of exposure. It lists no serious adverse event terms. These figures should therefore be read as the registry’s reported counts, not as evidence that no adverse events could occur or as a full account of safety monitoring.

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

The record establishes that CoMBAT was a completed pilot randomized trial comparing an intervention that added behavioral activation with a standard-of-care condition that included counseling and medication. It also identifies a self-reported missed-dose count as the primary outcome and describes follow-up at baseline, 3 months, and 6 months. These registry entries describe the study question and design, not the outcome findings.

The registry record does not report the numerical primary outcome means, standard deviations, group contrast, confidence interval, or p-value in the information available for interpretation. It therefore does not support a claim about whether reported missed-dose counts were higher or lower in either arm, how large a difference may have been, or how precisely it was estimated. The absence of numerical results in this record is not evidence that the groups were the same.

Likewise, the presence of a secondary outcome listing for fentanyl and opiate-positive urine toxicology screening does not establish a result for opioid use. No numerical result for that outcome is reported in the registry record. The stated aims of feasibility, acceptability, and preliminary efficacy also do not constitute findings; relevant numerical measures or conclusions are not reported in the information.

The safety record reports zero serious adverse events, zero other adverse events, and zero deaths in both arms, with 16 participants at risk per arm for the adverse-event categories. These observations describe the registry entries and do not establish that risk is absent or characterize uncommon events with high precision.

In short, the posted information permits a clear account of the trial’s structure and intended endpoint, but not an estimate of treatment effect. Any conclusion about the primary outcome would require its numerical results and the methods used to analyze them. Planning illustrations, if considered, should be read as hypothetical design calculations rather than evidence about what the trial observed.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it tests a combined approach in a randomized design while targeting outcomes related to treatment engagement. The intervention combines behavioral activation with counseling and medication, and the comparator includes counseling and medication. That structure makes the randomized contrast relevant to the added intervention package, while limiting conclusions about the independent contribution of each component.

The primary endpoint is a participant-reported count of missed doses. This is a practical measure for studying medication adherence, but it also illustrates how outcome choice shapes interpretation. Self-report can capture experiences that may not appear in administrative records, yet it can be affected by recall and reporting. Statistical summaries should therefore be interpreted alongside an understanding of how the endpoint was measured and what it represents.

The study is identified as a pilot, with feasibility, acceptability, and preliminary efficacy among its aims. Pilot studies can inform whether procedures and interventions are workable and help develop later research, but a pilot label does not establish that a trial was designed to estimate treatment effects precisely. The registry record does not report the original sample-size justification or numerical primary-outcome results, so it cannot establish the precision achieved.

The record also illustrates why statistical interpretation depends on more than the trial design. The endpoint includes multiple assessment times, a missing-data note applies to unadjusted means at the 3-month visit, and the detailed analysis plan is not reported. Without results and analysis details, readers cannot evaluate the observed trajectory, the effect estimate, uncertainty, or sensitivity to missingness. The appropriate statistical conclusion is therefore bounded: the trial’s question and design are documented, but the reported information is insufficient to quantify its primary outcome findings.

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 most important limitation for interpreting the posted results is that numerical primary outcome findings are not reported in the registry record. The primary outcome description identifies raw, unadjusted means at 6-month follow-up, but the actual values, dispersion estimates, and between-arm contrast are not present in the record details available for interpretation. Without an estimate and its uncertainty, the primary outcome cannot be evaluated for direction, magnitude, or precision.

The registry lists baseline and follow-up assessments at 3 and 6 months, but it does not state which time-point comparison was treated as the principal inferential test or how repeated measurements were handled. The analysis plan, including any covariate adjustment and uncertainty calculation, is not reported. The record also does not report multiplicity procedures despite listing 3 outcome measures and 3 analyses.

The primary endpoint is self-reported, so recall and reporting may affect measurement. The trial was unmasked, which may be relevant to participant-reported outcomes and counseling-based interventions. These are potential sources of measurement or performance bias; the record does not establish that they altered the results.

The record notes missing data for 2 participants in the CoMBAT experimental arm at the 3-month visit for unadjusted means by time point. It does not describe missingness in other analyses, reasons for missing data, or how missing outcomes were handled. The sample-size justification, interim analyses, and detailed statistical plan are also not reported in the registry record. Finally, the safety figures have limited interpretive detail: definitions and surveillance methods are not reported, and the zero recorded events do not establish that risk is absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CoMBAT Opioid Use Disorder: A Combined Medication and Behavioral Activation Treatment for People Living With Opioid Use Disorder — NCT04240093.
• Registry record last updated 2023-05-26; status last verified 2023-05.
• Results first posted 2023-05-26.
• 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

CoMBAT Opioid Use Disorder was a completed, randomized, parallel-group, unmasked pilot trial sponsored by Brown University. Enrollment was 44. The registry lists the study start as 2019-11-15 and primary completion as 2022-02-18.

The experimental condition combined behavioral activation, substance abuse and health navigation counseling, and medication for opioid use disorder. Standard of care included the counseling and medication. The primary outcome was the self-reported number of missed methadone or buprenorphine doses in the past 30 days, assessed at baseline and follow-up. The registry describes unadjusted means at 6 months and notes missing data for 2 experimental-arm participants at the 3-month visit for unadjusted means by time point.

Numerical primary outcome results, an effect estimate, and its precision are not reported in the registry record. The record lists fentanyl and opiate-positive urine toxicology screening as a secondary outcome. Safety entries report no serious adverse events, other adverse events, or deaths in either arm. Detailed statistical methods and the original sample-size justification are not reported.