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 Maintenance vs. Detoxification in Prescription Opioid Dependence (NCT00555425), a randomized phase 4 study. The primary outcome is Illicit Opioid Use.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00555425 |
| Phase | Phase 4 |
| Condition | Opiate Dependence |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 113 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
Population
People with prescription opioid dependence receiving primary care management and drug counseling in an office-based setting. The condition listed in the registry record is opiate dependence. Enrollment was 113.
Intervention
Buprenorphine/naloxone maintenance, described as reflecting usual care by primary care physicians and including weekly drug counseling and referral to ancillary services. The medication was to continue unchanged after the stabilization period.
Comparator
Buprenorphine/naloxone detoxification, also called the taper condition. The registry describes the first 4 weeks as the same stabilization period as maintenance, followed by tapering buprenorphine to zero over the next 3 weeks.
Primary question
During the 18-week treatment period, did maintenance or tapering differ in the mean percentage of scheduled urine samples that were negative for opioids? Urinalysis was based on scheduled weekly screenings. The registry’s stated aim was to determine whether maintenance, compared with detoxification, leads to decreased illicit opioid use in this care setting.
The question is about the average proportion of opioid-negative urine samples during the specified treatment period. It is not a direct measure of every aspect of opioid use, nor does it by itself establish what happened after the treatment period. The trial also listed secondary outcomes involving protective transfer, retention, cocaine use, HIV risk, patient satisfaction, and health status. Those outcomes address other aspects of treatment and experience, but they do not replace the primary urine-screening measure.
3. Trial Design
The registry describes a randomized, parallel-group, unmasked phase 4 trial. It lists enrollment of 113 and a completed status. The study started in 2008-07, and primary completion was recorded as 2013-05. Yale University is listed as the sponsor. The record does not report additional details about the randomization process or allocation concealment.
Participants were assigned to maintenance or tapering. Both conditions included buprenorphine/naloxone stabilization for the first 4 weeks. In the maintenance condition, buprenorphine was to continue unchanged for the remainder of the study. In the taper condition, the dose was to be tapered to zero over the next 3 weeks. The available arm description is truncated after stating that patients would not receive “ad”; further details of that description are not reported in the registry record. The maintenance description includes weekly drug counseling and referral to ancillary services, and the study summary describes primary care management and drug counseling in an office-based setting.
Unmasked means the registry does not describe blinding of participants or study personnel. That is relevant when considering measures that involve judgment or self-report; the primary outcome, however, was based on urine testing. The primary endpoint was assessed over 18 weeks. Its stated measurement was the mean percentage of opioid-negative urine samples from scheduled weekly screenings during treatment.
The record gives arm-level sample sizes and primary outcome estimates, but does not report the primary comparison’s inferential analysis. Details such as the statistical model, analysis population, handling of missing urine samples, or protocol-defined analysis plan are not reported in the registry record. Randomization supports a comparative design, but the posted summary alone cannot answer every question about trial conduct or analysis.
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: 289 Patients underwent assessment for eligibility, 29 did not meet inclusion criteria, 132 lost contact or chose other treatment, and 15 did not complete induction
Overall Study
| Stage | Taper Condition | Maintenance Condition |
|---|---|---|
| STARTED | 57 | 56 |
| COMPLETED | 6 | 37 |
| NOT COMPLETED | 51 | 19 |
Reasons for not completing this period:
| Reason | Taper Condition | Maintenance Condition |
|---|---|---|
| Missed Medication > 1 wk | 34 | 15 |
| Missed 3 physician management visits | 1 | 0 |
| Met criteria for protective transfer | 16 | 3 |
| Became pregnant and transferred care | 0 | 1 |
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 | Taper Condition | Maintenance Condition | Total |
|---|---|---|---|---|
| Participants analysed | 57 | 56 | 113 | |
| Age, Continuous | years | 30.3 (SD 8.8) | 30.5 (SD 9.8) | 30.4 (SD 9.3) |
| Sex: Female, Male: Female | Participants | 23 | 25 | 48 |
| Sex: Female, Male: Male | Participants | 34 | 31 | 65 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 | 4 | 8 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 53 | 52 | 105 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 56 | 52 | 108 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 3 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Illicit Opioid Use, measured over 18 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent of opioid negative urine samples |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean percentage of opioid-negative urine samples during 18 weeks of treatment. Urinalysis was based on scheduled weekly urine screenings. The measure captures the share of scheduled samples that tested negative for opioids, averaged within each treatment group. It therefore summarizes repeated biological measurements over the treatment period rather than relying only on participants’ reports of opioid use.
Urine screening is used in this study as an objective indicator relevant to illicit opioid use. Repeated scheduled testing can describe patterns across treatment, while the group mean offers a compact summary for comparing the randomized conditions. The measure remains specific to the samples collected: it does not describe use between screenings, the circumstances of any use, or outcomes after the 18-week period. Interpretation also depends on how missed or unavailable samples were treated. That handling is not reported in the registry record.
The registry reports the primary outcome as a mean with a 95% confidence interval. For the taper condition, the mean was 35.2, with a 95% confidence interval from 26.2 to 44.2. For maintenance, the mean was 53.2, with a 95% confidence interval from 44.3 to 62.0. These are group estimates for the percentage of opioid-negative samples, not percentages of participants who remained opioid-free. The registry record does not report a primary between-group test or an adjusted treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary estimates are 35.2 for the taper condition and 53.2 for maintenance, expressed as the mean percentage of opioid-negative urine samples during 18 weeks. The corresponding 95% confidence intervals are 26.2 to 44.2 and 44.3 to 62.0. The estimates therefore describe a higher average percentage in the maintenance group in this trial. The intervals express uncertainty around each group estimate; they do not themselves provide the registry’s formal test of the difference between groups.
The registry record does not report a primary comparison estimate, confidence interval for the between-group contrast, or p-value. It also reports no analyses in its analysis listing. Accordingly, the posted primary results support a descriptive comparison of the group means but do not give a registry-reported inferential conclusion about the size or precision of the treatment contrast. The apparent separation between group means should not be converted into a new difference or treated as a substitute for a reported comparison analysis.
The endpoint is an average across scheduled urine screenings, not a count of participants who had no opioid use, and not a direct measure of each participant’s complete experience over treatment. How the analysis handled missing or unscheduled samples is not reported in the registry record. If missing samples were common or differed between groups, that could affect the meaning of the averages; the posted summary does not permit an assessment of that possibility.
The trial was randomized, which is an important design feature for evaluating a contrast between assigned conditions. It was also unmasked. The outcome was based on urine testing, but unmasked treatment can still matter for care, engagement, attendance, or other processes that shape the data collected. The registry record does not report enough detail to evaluate those pathways or the analytic choices used to address them.
Secondary outcome entries cover other domains, and the posted secondary comparisons do not all answer the same question as the primary endpoint. Their interpretation is further limited because the registry does not report a multiplicity adjustment or a complete inferential plan. The primary results should therefore be read as estimates of a specific urine-screening measure in this trial, with uncertainty and analysis details that remain incompletely documented in the registry record. They are not, by themselves, a complete account of the comparative effects of the treatment strategies across all relevant outcomes.
9. Statistical Methods Explained
The primary endpoint is continuous: it is reported as the mean percentage of opioid-negative urine samples. A mean summarizes the central level of a measured quantity across observations. In this case, the registry presents a group-level average based on scheduled urine screenings during treatment. The measure is not a binary outcome at the participant level: a mean percentage of negative samples should not be interpreted as the percentage of participants who were opioid-free.
What do the confidence intervals convey?
A confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis that produced it. The registry reports a 95% confidence interval for each group’s primary mean: 26.2 to 44.2 for tapering and 44.3 to 62.0 for maintenance. These intervals characterize uncertainty in the group estimates. They are not intervals for the difference between groups, and they do not replace a formal comparison. The registry record does not report a confidence interval for the primary between-group contrast.
Confidence intervals are useful because an estimate alone can suggest more precision than the data warrant. A wider interval indicates less precision than a narrower interval, all else equal. Interpretation should consider both the point estimate and its interval, while remembering that the interval depends on the data and analysis assumptions. The registry does not report the method used to calculate the primary confidence intervals.
Why is the missing comparison analysis important?
A between-group analysis estimates the contrast associated with assignment to the randomized conditions and quantifies uncertainty around that contrast. Although the registry presents a mean and interval for each arm, it does not report a primary contrast, its interval, or a p-value. Separate arm-level intervals are not a substitute for a contrast interval: the uncertainty of a difference depends on the joint comparison, not merely on reading two intervals side by side. No new contrast is calculated for this interpretation.
The registry’s analysis listing records no analyses. That does not establish that no analysis was conducted; it means that an analysis is not posted in that listing. The statistical model, any covariate adjustment, and the primary analysis population are not reported in the registry record. It is therefore not possible to determine from the posted record whether the estimates reflect all randomized participants, participants with available urine measurements, or another defined set.
Why does missingness matter for repeated urine tests?
Scheduled testing creates the possibility of missing observations. If a sample is unavailable, the analysis must use some rule for including or excluding that occasion or participant. Different rules can change the estimand and the resulting summary. Missingness may also be related to treatment engagement or other outcomes, so the pattern of missing measurements can affect how representative the observed samples are. The registry record does not report the amount of missing primary outcome data, reasons for missingness, or the method used to handle it.
How should the secondary comparisons be read?
The posted secondary comparisons include a risk difference for the binary protective-transfer outcome and a mean difference for cocaine-positive urine samples. A risk difference expresses a contrast between group proportions; a mean difference expresses a contrast between group averages. These are different measures for different kinds of outcomes. The record provides unadjusted p-values for these posted comparisons, but does not report adjusted analyses. A p-value is a measure of how compatible the observed data are with a specified null model under the analysis assumptions; it is not the probability that a treatment effect is true or false.
When several outcomes or comparisons are examined, the chance of obtaining at least one apparently notable result can increase. Multiplicity methods address that issue, but the registry record does not report whether a correction or prespecified hierarchy was used. The secondary results should therefore be treated as exploratory evidence rather than as a set of independent confirmatory findings.
What do the sample-size illustrations mean?
The planning illustrations are recalculations based on observed effects, not the trial’s own design justification. They assume a two-sided significance level of 0.05, equal allocation, and a normal approximation, and use stated fractions of the observed effect. For non-time-to-event outcomes, the entries describe participants per arm for 80% or 90% power. These figures are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry record does not report its original sample-size justification or the assumptions used for trial planning.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes in addition to the primary endpoint. Testing multiple outcomes can increase the chance that at least one result appears notable by chance. A prespecified testing hierarchy or multiplicity adjustment can help control that problem, but neither is reported in the registry record. The posted secondary comparisons are unadjusted, so their p-values should not be interpreted as if they were the only tests conducted. The registry record does not report the complete analysis plan or indicate whether additional analyses were conducted but not posted.
Analysis populations are also not described in enough detail to determine who contributed to each outcome estimate. Although the registry gives arm-level sample sizes, it does not state whether the primary analysis followed an intention-to-treat principle, used an available-case approach, or used another population definition. The method used for the primary comparison is not reported, and the analysis listing records no analyses. These omissions limit assessment of how assignment, adherence, and availability of outcome measurements were handled.
The primary endpoint depends on scheduled weekly urine screenings, but the registry does not report the amount or pattern of missing urine data, reasons for missed samples, or the rule used to handle them. Missing observations can affect both the precision and interpretation of repeated-measure summaries. Without those details, it is not possible to determine whether the reported means represent the same underlying set of scheduled assessments in both groups or how sensitive the results are to missingness assumptions.
The registry record also does not report whether there were interim analyses, stopping rules, or a protocol-defined approach to multiple outcomes. Those matters should be treated as not reported in the registry record, rather than inferred from the completed status or the posted estimates. The absence of these details does not establish that a particular procedure was or was not used; it limits what can be concluded from the registry record alone.
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 |
|---|---|---|---|
| Taper Condition | 0 | 57 | 0.0% |
| Maintenance Condition | 0 | 56 | 0.0% |
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 |
|---|---|
| Taper Condition | 0 of 57 |
| Maintenance Condition | 0 of 56 |
The registry reports zero participants with serious adverse events among 57 at risk in the taper condition and among 56 at risk in the maintenance condition. It also reports zero participants affected by other adverse events among the same arm-specific numbers at risk. Death counts are not reported. No top serious adverse event terms are listed.
These entries are registry safety summaries. A zero recorded count means that the posted results list no affected participants for that category; it does not establish that no adverse experiences occurred outside the categories, time periods, or recording procedures represented in the registry. The record does not provide event-level detail, definitions, severity information beyond the serious-event grouping, or a fuller account of surveillance and attribution. It also does not explain how missing safety information was handled.
The figures should be read as descriptive counts, not as proof that the groups have identical safety profiles. With no posted comparative safety analysis, no formal estimate of a between-group difference is available in the registry record. The absence of reported deaths is not established by the entries because the death values are null. Safety interpretation is therefore limited to the specific recorded counts and the information the registry makes available.
12. What the Result Does, and Does Not, Mean
The primary results describe a higher mean percentage of opioid-negative urine samples in the maintenance group than in the taper group during the 18-week treatment period. The registry provides arm-level estimates and 95% confidence intervals, but does not report a primary between-group effect estimate, its confidence interval, or a p-value. The size and statistical precision of the primary contrast therefore cannot be stated from the registry record without creating a new calculation.
The result concerns scheduled urine screenings, not every instance of opioid use, and not the percentage of participants who were continuously free of opioid use. It also does not describe outcomes after the treatment period. Interpretation depends in part on missing-data handling, analysis population, and the statistical method used; those details are not reported in the registry record.
The randomized design provides a framework for comparing assigned treatment conditions, but the registry’s posted summary does not document all details needed to assess execution and analysis. The trial was unmasked, and the available record does not explain how adherence, missing screenings, or other post-assignment events were handled analytically. The endpoint is based on urinalysis, but it remains a specific measure rather than a complete account of clinical outcomes.
Secondary results cover additional outcomes, but not all listed outcomes have posted numerical results, and the registry does not report multiplicity handling. They therefore do not form a complete, confirmatory evidence set. Neither the primary estimates nor the secondary entries should be taken as a universal conclusion about every patient, setting, or outcome. They describe the results recorded for this trial and the limits of what can be inferred from those results.
13. Why This Trial Matters Statistically
This trial illustrates why the form of an endpoint matters. The primary outcome is a mean percentage of opioid-negative urine samples, a repeated-measure summary. It is distinct from an individual-level outcome such as the proportion of participants who never tested positive. Describing the estimand accurately prevents a group average from being mistaken for a claim about every participant.
It also illustrates the difference between arm-level summaries and a treatment contrast. Group means and their confidence intervals are informative, but a formal comparison requires an estimate of the contrast and its uncertainty. The registry reports the arm summaries but not the primary comparison analysis. Readers should not treat visual or numerical separation between arm estimates as a substitute for that analysis.
The contrast between a randomized design and incomplete registry analysis details is important for evidence appraisal. Randomization is a key design feature, while missing information about analysis populations, missing urine samples, and the statistical plan limits the ability to evaluate how the posted estimates were derived. Clear reporting of these details helps readers judge precision, bias risks, and the connection between a planned question and the analysis reported.
Finally, the secondary outcomes demonstrate why multiplicity matters. Several outcome domains are listed, but results are incomplete and posted comparisons are unadjusted. Interpreting each result independently as confirmatory would overstate the evidence. Statistical importance depends not only on an isolated estimate or p-value, but also on the endpoint’s role, analysis plan, uncertainty, and completeness of reporting.
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 primary limitation of the registry record is the absence of a reported between-group analysis for the primary endpoint. Arm means and confidence intervals are available, but the registry does not provide a contrast estimate, contrast interval, or p-value. The statistical method and analysis population are also not reported, so the exact basis of the posted arm summaries cannot be fully assessed.
The endpoint depends on scheduled urine screening, yet the record does not report missing-sample counts, reasons for missingness, or how unavailable samples were handled. This is important because the measure summarizes repeated observations during treatment. The posted information does not establish whether the observed screenings are complete or whether missingness differed between conditions.
The record gives limited detail about trial conduct beyond its randomized, parallel, unmasked design and the described treatment conditions. It does not report allocation concealment, adherence, treatment exposure, or the statistical plan. The available description of the taper arm is truncated. Further details of that description are not reported in the registry record.
Secondary outcome reporting is incomplete: numerical results are posted for only some of the listed domains, and the record does not describe multiplicity control or a prespecified hierarchy. The safety summary offers counts but no event-level detail, and death counts are not reported. These limitations do not invalidate the posted information, but they constrain how much can be concluded from it and make a fuller assessment dependent on details not available in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Buprenorphine Maintenance vs. Detoxification in Prescription Opioid Dependence — NCT00555425.
- Registry record last updated 2019-01-14; status last verified 2019-01.
- Results first posted 2017-01-24.
- 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
The registry record describes NCT00555425, “Buprenorphine Maintenance vs. Detoxification in Prescription Opioid Dependence,” as a completed randomized, unmasked, parallel phase 4 trial sponsored by Yale University. Enrollment was 113. The study began in 2008-07, with primary completion in 2013-05.
The primary endpoint was the mean percentage of opioid-negative urine samples from scheduled weekly screenings during 18 weeks of treatment. The registry reports arm-level means and 95% confidence intervals, but not a primary between-group analysis. Secondary outcomes cover several additional domains, with posted numerical results for some but not all listed outcomes. The analysis plan, missing-data handling, and multiplicity approach are not reported in the registry record.