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 Buprenorphine to Improve HIV Care Engagement and Outcomes (NCT01936857), a randomized phase 4 study. The primary outcome is Number of Participants With HIV Viral Suppression.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01936857 |
| Phase | Phase 4 |
| Condition | HIV, Substance Related Disorders |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 281 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oregon Health and Science University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people in Vietnam living with HIV who also have opioid dependence. The registry summary describes comparing treatment approaches for this population. It does not report further eligibility criteria or participant characteristics, so details such as age, gender, or baseline clinical status are not available in the registry record.
Intervention
The intervention was office-based treatment of opioid dependence with buprenorphine/naloxone. The study description places this treatment alongside HIV care in the HIV clinic and notes counseling as part of the new model being studied. Additional details about counseling or treatment delivery are not reported in the registry record.
Comparator
The comparison was referral to methadone maintenance therapy for treatment of opioid dependence. This reflects the existing model described in the registry summary for people with HIV and opioid dependence in Vietnam. The record does not provide further details about the referral process or the care participants received after referral.
Primary question
The primary outcome was the number of participants with HIV viral suppression at 12 months, defined as HIV-1 RNA < 200 copies/mL. The clinical question is whether the two treatment models differed in the number of participants meeting that definition. A single comparative result for this outcome is not reported in the registry record, so the record does not establish the direction or size of any difference.
3. Trial Design
BRAVO was a randomized, parallel-group Phase 4 trial sponsored by Oregon Health and Science University. The registry record reports enrollment of 281 and lists the study as completed. It began in 2015-07, with primary completion in 2019-03. The two trial groups were buprenorphine/naloxone and methadone maintenance therapy.
The comparison was between treatment models, not simply between drug names. In the buprenorphine/naloxone group, opioid-dependence treatment was office-based. The comparison group was referred to methadone maintenance therapy. The registry summary describes the setting as Vietnam and frames the study around how each model affects HIV care. It also identifies receipt of antiretroviral therapy and retention in HIV care as secondary outcomes.
The trial is listed as unmasked, meaning masking is not reported as part of its design. Further details of sequence generation, concealment of allocation, implementation of randomization, or any stratification are not reported in the registry record. Nor does the record describe whether participants could change treatment models during follow-up or how such changes were handled in analyses.
The at-risk denominators listed with the safety information are 141 for buprenorphine/naloxone and 140 for methadone maintenance therapy. These are the denominators for those safety figures; they do not by themselves describe the analysis population for every outcome. The record does not provide a detailed flow of enrollment, treatment initiation, follow-up completion, or inclusion in each analysis. These design and reporting details matter when interpreting comparisons, especially when outcome follow-up is incomplete.
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 | Buprenorphine/Naloxone | Methadone Maintenance Therapy |
|---|---|---|
| STARTED | 141 | 140 |
| COMPLETED | 107 | 115 |
| NOT COMPLETED | 34 | 25 |
Reasons for not completing this period:
| Reason | Buprenorphine/Naloxone | Methadone Maintenance Therapy |
|---|---|---|
| Sent to prison or 06 center | 11 | 12 |
| Lost to Follow-up | 10 | 7 |
| Death | 7 | 3 |
| Moved | 2 | 1 |
| Withdrawal by Subject | 1 | 0 |
| Side effect of medication | 1 | 0 |
| Other | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: Follow up viral suppression was not available for 50 buprenorphine group participants, and 33 of methadone group participants.
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 | Buprenorphine/Naloxone | Methadone Maintenance Therapy | Total |
|---|---|---|---|---|
| Participants analysed | 141 | 140 | 281 | |
| Age, Continuous | years | 38.0 (SD 5.8) | 38.6 (SD 6.4) | 38.3 (SD 6.1) |
| Sex: Female, Male: Female | Participants | 5 | 4 | 9 |
| Sex: Female, Male: Male | Participants | 136 | 136 | 272 |
| Race/Ethnicity, Customized: Kinh | Participants | 139 | 139 | 278 |
| Race/Ethnicity, Customized: Other | Participants | 2 | 1 | 3 |
| Region of Enrollment: Vietnam | participants | 141 | 140 | 281 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With HIV Viral Suppression, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with HIV viral suppression at 12 months. Suppression is defined in the registry record as HIV-1 RNA < 200 copies/mL. This is a binary outcome at the participant level: a participant either meets the stated threshold or does not, based on the measurement used for the endpoint. The registered outcome is expressed as a count of participants, rather than as a continuous summary of viral RNA values.
Viral suppression is used as an indicator of HIV status under the threshold specified for this trial. In general, a threshold-based endpoint can make a clinical outcome straightforward to classify and compare between groups. It also loses information about how far individual measurements fall above or below the threshold. The registry record does not describe the laboratory procedures, the handling of measurements near the threshold, or whether repeat measurements were used.
The outcome timeframe is 12 months. The record notes that follow-up viral suppression was unavailable for 50 participants in the buprenorphine group and 33 participants in the methadone group. It does not give the count meeting the suppression definition in either group or a comparative estimate. Therefore, the endpoint definition is available, but the registry record does not report a single result that quantifies the comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clear treatment-model comparison and a clinically interpretable primary endpoint: the number of participants with HIV viral suppression at 12 months, using the threshold HIV-1 RNA < 200 copies/mL. However, it does not supply a single comparative result for that endpoint. The record notes that follow-up viral suppression was unavailable for 50 buprenorphine group participants and 33 methadone group participants, and states that the primary outcome has several categories or time points and is not reduced to one comparison.
That reporting means no direction or magnitude of a primary-outcome difference can be stated from this record. It also means there is no reported confidence interval or statistical test for a single comparison to interpret. A missing estimate is not evidence that the groups were the same, and it is not evidence that they differed. The registry record does not report the primary outcome counts by group in a form that supports a standalone comparative statement.
The record lists receipt of antiretroviral therapy and retention in HIV care as secondary outcomes. It reports five outcome measures overall, but does not include analysis results for them in the registry record described in the registry record. It records zero analyses. This is a statement about what is registered, not proof that no analyses were conducted elsewhere. The registry information does not provide estimates, uncertainty intervals, or tests for those secondary outcomes.
The safety information lists serious adverse event figures of 10 for buprenorphine/naloxone and 4 for methadone maintenance therapy, with at-risk denominators of 141 and 140, respectively. Other adverse event figures are 23 and 3, and deaths are listed as 7 and 3, respectively. These are descriptive registry figures; the record does not provide a comparative statistical analysis or enough detail to infer causation. The safety section explains how to read these counts without treating them as a definitive comparison.
For any outcome, the precision of a comparison depends on the estimated effect and its uncertainty, not simply on whether a test crosses a significance threshold. Since a primary comparative estimate and its uncertainty are not reported in the registry record, the precision of the primary-outcome comparison cannot be assessed from these results. Conclusions should be limited to the registered design, endpoint definition, follow-up gaps, and reported safety counts.
9. Statistical Methods Explained
Randomization assigns participants to study groups by chance, with the aim of reducing systematic differences between groups at the outset. In general, this supports a fairer comparison than choosing treatment according to participant or clinician preference. The registry record labels this trial randomized and parallel, but does not describe how the random sequence was generated, how assignment was concealed, or how randomization was implemented. Those details are not reported in the registry record.
What does a parallel-group comparison mean?
In a parallel design, participants are assigned to a treatment group and followed in that group rather than switching through multiple assigned treatments as part of the design. BRAVO compared office-based buprenorphine/naloxone treatment with referral to methadone maintenance therapy. The record does not explain how participants who did not follow their assigned treatment or who changed treatment were handled in the analyses. It also lists masking as none. In general, lack of masking can affect behavior, care, or outcome assessment, depending on the outcome and trial procedures. The record does not describe outcome-assessor masking or measures to limit those effects.
How should the primary outcome be understood?
The primary outcome is a count of participants meeting a binary definition at 12 months: HIV-1 RNA < 200 copies/mL. A binary outcome reduces each participant’s measurement to whether the stated criterion was met. A comparison might be reported as counts by group, a difference in proportions, a relative measure, or another estimate, with an uncertainty interval. The registry record does not provide a single primary comparison or a reported uncertainty interval, so none of those comparative quantities can be interpreted from the record.
In general, a confidence interval describes a range of values compatible with the data and the statistical method used, while reflecting sampling uncertainty. A narrow interval indicates greater precision than a wide interval, but interpretation also depends on the endpoint and the range of values considered meaningful. No confidence interval for the primary comparison is reported in the registry record. A p-value, if available, would address compatibility with a specified null hypothesis under a particular test; it would not by itself describe effect size or clinical importance. No primary-outcome p-value is reported in the registry record.
What do the sample-size assumptions describe?
The sample-size material is described as a planning illustration computed from the observed effect, not as the trial’s original design justification. Its assumptions include a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration considers detecting a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed around those assumptions or that a particular effect was detected.
Sample-size planning asks how many participants would be needed under specified assumptions to detect a target effect with a chosen probability. That probability is a planning concept, not the probability that a finding is true. Any sample-size illustrations must therefore be read as hypothetical planning scenarios, never as observed power. The record does not report the trial’s own sample-size justification. No particular planning count or effect size is stated in the registry record details described for this analysis.
The planning description notes that time-to-event examples use a total number of events, while other examples use participants per arm. This distinction is general: time-to-event calculations are often driven by the number of outcome events, whereas calculations for other endpoint types may be expressed in participants. The primary outcome in BRAVO is a participant count, but the registry record does not provide a single comparison from which to judge a planning illustration as a summary of the primary result.
Why can over-dispersion matter?
For count outcomes, a simple statistical model may assume that variation follows a particular relationship to the average count. Over-dispersion means the data vary more than that model expects. In general, failing to account for over-dispersion can make uncertainty estimates too small and tests too optimistic. This is a general statistical consideration, not a reported feature or analysis choice in BRAVO. The record does not specify a model for the primary outcome, a dispersion adjustment, or any other estimation procedure.
The registry lists the primary outcome as a count of participants, but also indicates that the outcome information involves several categories or time points and is not reduced to one comparison. Without a reported analysis specification, it is not possible to determine which model, contrast, or handling of repeated measurements was used. The record does not report an adjustment for baseline factors, a method for dealing with missing endpoint data, or an analysis population definition. Those are important components of a reproducible statistical analysis, but they are not described in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures, including the primary outcome and secondary outcomes of receipt of antiretroviral therapy and retention in HIV care. It records zero analyses. The registry information does not describe how many comparisons were planned, how outcomes or time points were selected for analysis, or whether any adjustment for multiple testing was planned or performed. The multiplicity strategy is therefore not reported in the registry record.
In general, examining multiple outcomes, time points, or subgroup comparisons can increase the chance of finding an apparently notable result by chance. Methods for handling multiplicity can include prioritizing a primary outcome, adjusting tests, or treating secondary findings as exploratory. Which approach is appropriate depends on the analysis plan. The registry record does not state which approach was used for this trial, so no claim about multiplicity control is warranted.
Missing primary-outcome follow-up is explicitly noted: viral suppression was unavailable for 50 participants in the buprenorphine group and 33 in the methadone group. Missing outcome data can affect both the number of observations contributing to a comparison and the interpretation of the estimate. In general, the impact depends on why values are missing and how the analysis handles them. The reasons for missing follow-up, any imputation or weighting method, and any sensitivity analyses are not reported in the registry record.
The analysis population is also not specified. The record does not say whether the primary analysis included participants according to randomized assignment, treatment received, or another rule, and it does not provide a participant flow for each outcome. Without an analysis population definition and a missing-data strategy, it is not possible to assess how the unavailable follow-up values were incorporated into a primary comparison.
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 |
|---|---|---|---|
| Buprenorphine/Naloxone | 10 | 141 | 7.1% |
| Methadone Maintenance Therapy | 4 | 140 | 2.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Buprenorphine/Naloxone | 7 of 141 |
| Methadone Maintenance Therapy | 3 of 140 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Buprenorphine/Naloxone | 23 of 141 |
| Methadone Maintenance Therapy | 3 of 140 |
Most frequent serious adverse event terms
| Event term | Organ system | Buprenorphine/Naloxone | Methadone Maintenance Therapy |
|---|---|---|---|
| Accident, trauma, or external factor | Injury, poisoning and procedural complications | 6 of 141 | 1 of 140 |
| AIDS-related | Immune system disorders | 3 of 141 | 2 of 140 |
| General disorders | 1 of 141 | 1 of 140 | |
| Respiratory | Respiratory, thoracic and mediastinal disorders | 1 of 141 | 0 of 140 |
| Nephrogenic | Renal and urinary disorders | 1 of 141 | 0 of 140 |
| Malaise | General disorders | 1 of 141 | 0 of 140 |
| Psychiatric | Psychiatric disorders | 1 of 141 | 0 of 140 |
| Suicide attempt | Psychiatric disorders | 1 of 141 | 0 of 140 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Buprenorphine/Naloxone | Methadone Maintenance Therapy |
|---|---|---|---|
| Unintentional injury | Injury, poisoning and procedural complications | 12 of 141 | 2 of 140 |
| Suspected infection | Infections and infestations | 5 of 141 | 0 of 140 |
| Gastrointestinal | Gastrointestinal disorders | 4 of 141 | 0 of 140 |
| Neuropathy | Nervous system disorders | 1 of 141 | 1 of 140 |
| Headache | General disorders | 2 of 141 | 0 of 140 |
| Abnormal lab result | General disorders | 1 of 141 | 0 of 140 |
| Vascular | Vascular disorders | 1 of 141 | 0 of 140 |
| Cardiac | Cardiac disorders | 1 of 141 | 0 of 140 |
| Allergic reaction (non-study medication) | Immune system disorders | 1 of 141 | 0 of 140 |
| Malaise | General disorders | 1 of 141 | 0 of 140 |
Serious events with the highest arm-level rate: accident, trauma, or external factor (4.3%), aids-related (2.1%), respiratory (0.7%), nephrogenic (0.7%), malaise (0.7%).
The registry record lists serious adverse event figures for the buprenorphine/naloxone group with 141 at risk and for the methadone maintenance therapy group with 140 at risk. The reported serious figures are 10 and 4, respectively. Other adverse event figures are 23 and 3, and deaths are listed as 7 and 3. These are descriptive counts in the registry record; they are not, by themselves, an adjusted comparison or evidence that treatment caused an event.
The record also lists serious-event terms and percentages: Accident, trauma, or external factor at 4.3%; AIDS-related at 2.1%; and Respiratory, Nephrogenic, Malaise, and Psychiatric at 0.7% each. These terms should be read as the registry’s reported categories. The record does not give enough detail to assign these term percentages to a particular treatment group or to determine how categories may overlap.
In general, safety counts need context: how events were defined, whether they refer to events or participants, the duration of observation, and whether participants could have more than one event. Those details and a statistical comparison are not reported in the registry record. The figures should therefore be read as registry-reported safety information, not as proof of a difference in risk or a causal effect.
12. What the Result Does, and Does Not, Mean
The registry record establishes that BRAVO was a randomized parallel-group trial comparing office-based buprenorphine/naloxone treatment with referral to methadone maintenance therapy in Vietnam. It specifies HIV viral suppression at 12 months, defined as HIV-1 RNA < 200 copies/mL, as the primary outcome. It also identifies antiretroviral therapy receipt and retention in HIV care as secondary outcomes. These details clarify what the trial set out to compare and what outcomes it registered.
The record does not provide a single comparative estimate for the primary outcome. It also does not report estimates or uncertainty intervals for the secondary outcomes in the information available for this analysis. Consequently, it cannot establish from these registry results whether one group had more participants meeting the viral suppression threshold, how large any difference was, or how precisely such a difference was estimated. The absence of a reported comparison should not be interpreted as evidence of equivalence or absence of an effect.
Follow-up viral suppression was unavailable for 50 participants in the buprenorphine group and 33 in the methadone group. That missingness is relevant because incomplete outcome data can affect estimates and their precision, depending on the reasons for missing values and the analysis method. The registry record does not report those reasons or how missing outcomes were handled.
The safety figures provide descriptive counts, but do not establish that an event was caused by either treatment or that the groups differed statistically. Likewise, planning illustrations based on an observed effect are not observed power and do not substitute for reported trial estimates. A full interpretation would require comparative outcome results, their uncertainty, and details of the analysis and missing-data handling. Those items are not reported in the registry record.
13. Why This Trial Matters Statistically
BRAVO is statistically informative as a comparison of two care models rather than only a comparison of medications. The buprenorphine/naloxone approach was office-based, while the comparison involved referral to methadone maintenance therapy. The trial’s registered focus on viral suppression, antiretroviral therapy receipt, and retention in HIV care connects treatment of opioid dependence with measures of HIV care engagement. This makes the choice and definition of outcomes central to understanding the question the trial addressed.
The primary endpoint is threshold-based and measured at 12 months. That makes its interpretation depend not only on the endpoint definition but also on the completeness of follow-up and the way the result is summarized. The record notes unavailable viral suppression follow-up in both groups, but does not report a single comparative estimate or the method used to address missing observations. This highlights why endpoint counts alone, without a clear comparison and uncertainty, are not enough to assess a treatment contrast.
The study also illustrates an important distinction between statistical planning and results. Planning illustrations based on an observed effect can show how hypothetical sample-size needs vary under stated assumptions. They do not reveal whether a trial met its original design target, and they are not evidence of observed power. The registry record does not report the trial’s own sample-size justification.
Finally, registry completeness shapes what can be learned from posted results. The record gives the randomized parallel design and key outcome definitions, but does not report the statistical model, primary comparative estimate, uncertainty, or missing-data approach. Clear reporting of these elements is essential for judging the strength and precision of a clinical comparison. Here, the registered question is identifiable, while the statistical result needed to answer it is not reported in the registry record.
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 central limitation for interpretation is that the registry record does not reduce the primary outcome to a single comparison. It defines the endpoint and its timeframe, but does not report group-specific suppression counts or a comparative estimate. The stated issue of several categories or time points further prevents a single summary from being interpreted from the record. Without an estimate and uncertainty interval, neither the size nor precision of the primary comparison can be assessed.
Follow-up viral suppression was unavailable for 50 participants in the buprenorphine group and 33 in the methadone group. The reasons for unavailable measurements, the timing of missingness, and its handling in any analysis are not reported in the registry record. This limits assessment of potential bias and of how representative the outcome data are of the enrolled participants.
The registry does not describe random-sequence generation, allocation concealment, treatment changes, adherence, or analysis populations. It also does not report the statistical model, any covariate adjustment, or sensitivity analyses. These omissions do not show that the procedures were absent; they mean the relevant details are not reported in the registry record.
The trial is listed as unmasked, but the record does not explain masking of outcome assessors or other steps used to reduce possible ascertainment effects. Participant characteristics and further eligibility details are also not reported. Finally, the safety figures are not accompanied by definitions, event-level detail, or comparative analyses. These reporting limits require cautious interpretation of both effectiveness outcomes and safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Buprenorphine to Improve HIV Care Engagement and Outcomes — NCT01936857.
- Registry record last updated 2022-05-17; status last verified 2022-04.
- Results first posted 2020-06-24.
- 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
BRAVO (NCT01936857) was a completed, randomized, parallel-group Phase 4 trial sponsored by Oregon Health and Science University, with enrollment of 281. It compared office-based buprenorphine/naloxone treatment for opioid dependence with referral to methadone maintenance therapy in Vietnam. The study started in 2015-07 and primary completion was in 2019-03. The trial was listed as unmasked.
The primary outcome was the number of participants with HIV viral suppression at 12 months, defined as HIV-1 RNA < 200 copies/mL. The registry record notes unavailable follow-up viral suppression for 50 buprenorphine group participants and 33 methadone group participants. Receipt of antiretroviral therapy and retention in HIV care were listed as secondary outcomes. A single comparative primary-outcome result, its uncertainty, and the analysis methods are not reported in the registry record.