Buprenorphine Treatment for Opioid Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Buprenorphine Treatment for Opioid Dependence (NCT02187198), a randomized phase 3 study. The primary outcome is Urine Toxicology for Opiate Use.

2. Clinical Question

In statistical terms, the intended contrast is between outcomes under assignment to the lower and higher buprenorphine dose ranges. The urine testing is described as weekly during study participation, so the endpoint concerns evidence of opioid use across the study period rather than a single measurement at the end. The record does not specify whether the primary comparison was intended to use every weekly result, a participant-level summary, or another way of handling repeated measurements. That detail is not reported in the registry record.

3. Trial Design

The registry describes a Phase 3, randomized, parallel-group study with no masking. Yale University is listed as the sponsor. The record lists 9 enrolled participants, and the study status is completed. The start date is 2015-03 and the primary completion date is 2022-02-01. These dates describe the registry record; they do not, by themselves, explain the duration of recruitment or follow-up.

Participants were assigned to a low-dose or high-dose buprenorphine arm. The low-dose arm is described as receiving 8/2mg or less for 12 weeks. The high-dose arm is described as receiving 16-24mg for 12 weeks. There is no listed untreated or placebo comparator. Because masking is listed as none, the study is described as open-label: treatment assignment was not masked according to the registry entry.

Randomized allocation is intended, in general, to make treatment groups comparable with respect to both measured and unmeasured characteristics at the point of assignment. With a small enrollment, chance imbalances can nevertheless occur. The record does not report the randomization sequence method, allocation concealment, or whether stratification was used. These details are not reported in the registry record.

The primary outcome is urine toxicology for opiate use during Weeks 1-12. The brief description also identifies treatment retention and use of other drugs of abuse as outcomes of interest. The record lists 2 outcome measures, but detailed comparative results and analysis outputs are not reported. The registry does not describe the statistical plan, the treatment of missed tests, or the analysis population; those details are not reported in the registry record.

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

Reasons for not completing this period:

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 Urine Toxicology for Opiate Use, measured over Weeks 1-12.

The primary endpoint is titled “Urine Toxicology for Opiate Use.” It is recorded in participants, with the measure described as a count of participants. Urine toxicology is intended to document opioid use during the study. The registry description says screening was to be completed weekly during participation, over the 12-week study, and gives the endpoint timeframe as Weeks 1-12.

As a general statistical point, biological testing can provide an objective indicator of recent substance exposure and can complement self-reported use. Repeated measurements can also describe whether evidence of use appears at different times during follow-up. However, the meaning of a participant count depends on the rule used to combine repeated tests. For example, an analysis might classify participants according to whether any test was positive, or it might analyze results over time. The registry record does not state which rule was used for this endpoint.

The title and description identify the outcome being monitored, but they do not report the number of participants with a positive test or a comparison between dose groups. The registry record also does not report how missing or unusable urine samples were handled. Accordingly, the endpoint definition alone does not establish the direction or size of any difference between treatment assignments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance rather than by a clinician’s or participant’s choice. This can reduce systematic differences between groups at the start of a study and supports a fair comparison of outcomes under the assigned interventions. Randomization does not guarantee identical groups, and chance imbalances can be important when enrollment is small. The registry identifies the study as randomized but does not describe how the sequence was generated, how assignments were concealed before enrollment, or whether randomization used blocks or strata. Those methods are not reported in the registry record.

The comparison is between the low-dose and high-dose buprenorphine arms. Because there is no placebo arm listed, the trial’s contrast concerns dose assignment rather than treatment versus no treatment. The record also describes no masking. As a general matter, open-label designs can influence expectations, participant behavior, co-interventions, and decisions about study procedures. The registry does not report whether urine-testing staff were masked to assignment.

What is the endpoint estimand?

An estimand is the precise treatment contrast a study seeks to quantify, including the outcome, population, treatment conditions, and approach to events such as treatment discontinuation or missing measurements. The registry identifies a participant-count endpoint for urine toxicology during Weeks 1-12, but does not give enough detail to reconstruct the full estimand. In particular, the record does not specify whether a participant was counted after any positive result, according to a scheduled visit, or by another rule. Nor does it explain whether participants who discontinued treatment continued to provide urine samples or how such discontinuation affected the endpoint.

These distinctions matter because urine tests are described as repeated weekly measurements. A count of participants with any evidence of use would summarize each person once, whereas an analysis of all weekly tests would retain information about timing and repeated observations. Those approaches can target different questions and require different methods. The registry record does not report which approach was used.

How should a confidence interval be understood?

In general, a confidence interval describes the range of values compatible with an estimate under a statistical method and its assumptions. It communicates uncertainty about the estimated contrast, not the probability that a particular treatment effect is true. A narrow interval indicates greater precision than a wide interval, all else equal. The registry record does not report a confidence interval for the primary outcome, so there is no interval to interpret for this comparison.

A test of statistical significance is also not a substitute for an effect estimate. A p-value, when reported, measures how incompatible the observed data are with a specified null model under the test’s assumptions. It does not state the size or clinical importance of an effect. No primary-outcome test result is reported in the registry record, and the statistical plan, including the test or model, is not reported.

What does the sample-size planning language mean?

The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation. They also describe planning illustrations based on a stated fraction of an observed effect. In general, such calculations estimate the group size that would be needed to detect a chosen effect under assumed conditions. They are planning illustrations, not observed power and not evidence that a study had a particular probability of detecting an effect after the results were known.

Planning calculations depend on assumptions about the outcome, effect size, variability or event frequency, allocation, and analysis. If those assumptions do not match the eventual data or analysis, the illustration may not reflect the precision of the study’s actual result. The registry record does not report a trial-specific sample-size justification or a complete statistical design rationale. The stated planning assumptions should not be mistaken for the trial’s own documented design process.

Why does the sparse outcome record matter?

Statistical interpretation depends on both the design and the observed outcomes. A registry entry that names an outcome but supplies no group-specific result cannot support a calculation of a treatment contrast. It also cannot establish whether the analysis respected random assignment, how repeated tests were summarized, or how missing observations were handled. Those are not minor presentation details: they define what the estimate represents and how reliable its uncertainty assessment may be.

For this study, the available record supports a description of the randomized dose comparison and urine-testing schedule. It does not support a numerical efficacy conclusion. The analysis method, outcome results, and uncertainty measures are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines multiple outcomes, time points, treatment contrasts, or statistical tests. In general, the more hypotheses tested, the greater the chance that at least one result may appear statistically notable by chance if no adjustment or prespecified hierarchy is used. The registry summary names treatment retention, opioid use, and other drug use as outcomes of interest, and the record lists 2 outcome measures. The primary urine toxicology description also involves weekly testing during Weeks 1-12. These features make the analysis plan relevant to interpretation.

The registry record does not report a multiplicity strategy, such as a hierarchy of endpoints, adjustment across comparisons, or identification of a single primary test. It also does not report the statistical analysis plan. No inference can be made about whether any multiplicity procedure was used outside what is documented in the registry record.

Missing-data handling is not reported. In general, missed urine tests can affect a participant-level outcome if the rule for classification depends on observed tests. Treating unobserved tests as negative, excluding participants with missing tests, or using a model that accommodates incomplete repeated measurements can lead to different interpretations. The registry does not state which approach, if any, was used.

The analysis population is likewise not reported in the registry record. It is not specified whether the primary analysis included everyone as randomized, only participants who completed treatment, or another defined group. The presence of randomized assignment alone does not establish which participants contributed to the posted endpoint analysis.

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 serious adverse-event listing reports 0 serious events in the low-dose arm among 5 participants at risk and 0 in the high-dose arm among 4 participants at risk. It also lists 0 other adverse events in each arm and 0 deaths in each arm. These are counts recorded in the registry and should be read as such.

Zero recorded events does not establish that an intervention has no safety risks. In general, small groups provide limited information about uncommon events, and a study’s ability to detect harms depends on its size, duration, event definitions, and completeness of reporting. The treatment period described for the arms is 12 weeks; the registry record does not provide further detail on the adverse-event collection window or definitions.

The record does not list serious adverse-event terms. The absence of listed terms alongside zero serious events does not supply evidence about harms that were not collected, defined, or reported. These figures are a limited safety description, not a comprehensive estimate of risk and not a basis for comparing safety reliably between dose ranges.

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

The record establishes that a randomized, open-label, parallel-group study compared low-dose and high-dose buprenorphine for prescription opioid dependence. It identifies urine toxicology for opiate use during Weeks 1-12 as the primary outcome and describes weekly screening. It also records treatment retention, opioid use, and other drug use as outcomes of interest. These design details clarify the question the trial was intended to address.

The record does not report comparative urine toxicology results, an effect estimate, a confidence interval, or a test of the primary comparison. It therefore does not show whether the recorded outcome differed between the dose arms, nor does it show the magnitude or precision of any difference. Missing comparative results should not be interpreted as evidence of no difference.

The enrollment of 9 is relevant to how much information the trial could contribute, especially for outcomes that may be uncommon or variable. In general, limited enrollment can produce imprecise estimates and may make baseline imbalances from chance more consequential. However, without group outcome results, it is not possible to describe the actual uncertainty of an efficacy estimate or determine whether observed findings were consistent across the weekly testing period.

The safety figures list no recorded serious adverse events, other adverse events, or deaths in the groups. These counts do not demonstrate absence of risk, particularly in a small study. They also do not answer the efficacy question.

Accordingly, the registry entry documents a study question, design, endpoint, and limited safety counts, but does not provide the outcome analysis needed to assess the comparative efficacy of the dose ranges. A treatment recommendation or conclusion about clinical benefit cannot be drawn from the information reported in the registry record.

13. Why This Trial Matters Statistically

This trial matters statistically because it asks a comparative dose question rather than comparing treatment with no treatment. A randomized design is suited in principle to estimating differences between assigned dose strategies, while the parallel-group structure makes the treatment arms the basis of that contrast. The record specifies low-dose and high-dose ranges and a 12-week treatment period, allowing the intended comparison to be described clearly.

The primary outcome also raises an important measurement issue: urine toxicology is described as weekly, while the endpoint is expressed as a count of participants. Repeated tests can capture changes over time, but reducing those results to a participant count requires an explicit summary rule. Without that rule and the analysis, readers cannot tell precisely what outcome contrast was estimated. This is a general lesson for trials with repeated binary or categorical measures.

Enrollment of 9 underscores why precision and uncertainty would be especially important to report. A group comparison without confidence intervals can be difficult to evaluate, and a small study may leave substantial uncertainty even when an estimate is available. Here, the registry does not report the comparative endpoint findings, so the intended statistical question cannot be answered from the entry.

The registry record also illustrates the distinction between a registered design and an analyzed result. Knowing the planned endpoint does not reveal the observed data, the analysis population, the handling of missing tests, or the statistical methods actually used. For clinical researchers, those details are essential for judging what a result means and how broadly it can be interpreted.

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 statistical interpretation is that comparative efficacy results are not reported in the registry record. The primary endpoint is named and its timeframe is described, but group-specific urine toxicology findings, an effect estimate, an uncertainty interval, and a statistical test are absent. As a result, the dose comparison cannot be quantified from the record.

The endpoint’s repeated-measure structure is not fully specified. Weekly urine testing is described, but the record does not state how test results were combined into the participant count or how missed, invalid, or unavailable tests were treated. The statistical model and analysis population are also not reported. These gaps prevent a reader from assessing the endpoint definition and analysis in detail.

Enrollment was 9, limiting the amount of information available for comparisons and safety assessment. The record does not describe participant characteristics, eligibility criteria, baseline balance, or the allocation procedure beyond identifying the trial as randomized. Masking is listed as none, and the record does not clarify whether outcome assessors or laboratory staff were masked.

The registry entry does not report a multiplicity plan, a full statistical analysis plan, or a trial-specific sample-size justification. The dates and completed status provide administrative context but do not resolve these analytical uncertainties. The safety counts are also limited: zero recorded events do not rule out harms, and the record does not give detailed event definitions or collection procedures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Buprenorphine Treatment for Opioid Dependence — NCT02187198.
• Registry record last updated 2023-03-10; status last verified 2023-03.
• Results first posted 2023-03-10.
• 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

NCT02187198 is a completed Phase 3 randomized, open-label, parallel-group study sponsored by Yale University. It enrolled 9 participants and compared low-dose buprenorphine, described as 8/2mg or less, with high-dose buprenorphine, described as 16-24mg, over 12 weeks. The study concerns prescription opioid dependence.

The primary endpoint is urine toxicology for opiate use during Weeks 1-12, with testing described as weekly. The registry record does not report a comparative primary-outcome result, statistical analysis, or confidence interval. It lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each arm. These counts do not establish the absence of risk or answer the efficacy question.