Buprenorphine as Adjunct to Outpatient Induction Onto Vivitrol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Buprenorphine as Adjunct to Outpatient Induction Onto Vivitrol (NCT03113409), a non-randomized phase 2, phase 3 study. The primary outcome is Percentage of Patients Who Receive the Second Injection of XR-NTX..

2. Clinical Question

3. Trial Design

The registry lists this as a Phase 2 and Phase 3 study with non-randomized allocation, no masking, and a single-group model. Its status is terminated. The listed start date is 2017-06-01, and the primary completion date is 2020-12-01. The record does not report why the study was terminated.

The brief summary describes an open-label outpatient pilot intended to examine methods for facilitating induction and stabilization onto XR-NTX. It states a planned enrollment of 30 participants. The registry enrollment figure is 10. These are different descriptions: the planned enrollment is not the number listed as enrolled in the record.

The three procedures vary in their induction schedules and continuation of buprenorphine. Procedure 1 is described as a 5-day induction with increasing oral naltrexone doses. Participants receive XR-NTX on day five with buprenorphine, then continue buprenorphine for 4 weeks until the second XR-NTX dose. Procedure 2 uses a 10-day induction with daily buprenorphine and increasing daily oral naltrexone doses beginning on day 2; buprenorphine does not continue beyond day 10. Procedure 3 has the same described 10-day induction schedule, but buprenorphine continues for 4 weeks until the second XR-NTX dose. Procedures 2 and 3 are described as receiving another XR-NTX dose 4 weeks after the day 10 dose.

The registry's overall model is single-group, while the procedure descriptions distinguish three approaches. The primary endpoint is specifically tied to Procedure 1. The record does not report a randomized comparison among procedures, nor does it report an analysis that compares their outcomes. A protocol, allocation rationale, or explanation for the relationship between the single-group model and the three procedure descriptions is 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:

Analysis population for the primary outcome, as defined in the registry: all participants enrolled in the study (Procedure 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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Who Receive the Second Injection of XR-NTX., measured over 4 weeks after 1st injection.

The primary endpoint is the percentage of patients who receive a second XR-NTX injection, with the timeframe stated as 4 weeks after the first injection. The endpoint description focuses on participants who initiated Procedure 1 and completed the study; the population description instead says all participants enrolled in the study in Procedure 1. These descriptions do not fully clarify whether the intended denominator includes every enrollee or only people who initiated the procedure and completed follow-up.

Receipt of the second injection is a binary outcome: each participant is classified according to whether the event occurred. The registry lists the unit as participants and the parameter as a count of participants, even though the endpoint title refers to a percentage. A percentage can describe the share of a defined group reaching the event, but interpreting it requires a clear numerator, denominator, and handling of participants whose status is unknown. Those details are not reported in the registry record.

This endpoint is used to describe completion of a specified step in the induction schedule. In general, a process endpoint can indicate whether participants reached a planned treatment milestone; it does not by itself establish the comparative effect of one procedure over another. The registry record does not report the observed count or percentage for the primary endpoint, so the endpoint's result and precision cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on how outcomes are defined, who is included in the analysis, and how uncertainty is represented. For this study, the primary outcome is binary: receipt of the second XR-NTX injection is the event, and not receiving it is the other outcome state. A count of participants with the event is not the same as a percentage. To interpret a percentage, readers need both a defined event count and a defined denominator. The registry describes the endpoint as a percentage but also lists the unit as participants and the parameter as a count. It does not report an observed result.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. For a binary outcome, an interval around a proportion can show how imprecise that estimate may be. An interval is not a range containing a known value with certainty, and it does not correct for design limitations, missing data, or a poorly defined analysis population. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed.

What can a single-group design establish?

A single-group description focuses on outcomes within a group rather than on a randomized contrast between groups. An observed proportion in one group could describe how often an event occurred in that study population. It would not, by itself, show what would have happened under a different procedure or establish that a procedure caused the observed outcome. The record lists non-randomized allocation and a single-group model; it does not report an adjusted comparison or randomized assignment across the three described procedures. The registry also does not report the analysis population and procedure assignment details needed to interpret any between-procedure comparison.

Why does the outcome definition matter?

The endpoint description refers to participants who initiated Procedure 1 and completed the study, whereas the population description refers to all participants enrolled in Procedure 1. These definitions may include different people if some enrolled participants did not initiate the procedure or did not complete follow-up. This is a general reason that an analysis should state its population and denominator clearly. The registry does not resolve the difference in wording, report participant flow, or specify how an unknown injection status was handled.

For a binary endpoint, missing outcome status cannot simply be treated as either an event or a non-event without an explicit rule. Different rules can change an estimate, especially when the number of participants is limited. The registry record does not report a missing-data method, sensitivity analysis, or count of participants with missing primary outcome information. No missing-data assumptions should therefore be attributed to the study.

What do the planning assumptions mean?

The registry describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Those are assumptions for a planning calculation, not a description of the trial's own design. In particular, equal allocation between two arms does not match the registry's listed non-randomized, single-group design. The record does not report a protocol-based sample-size justification or enough primary outcome information to assess the illustrated calculations. Sample-size illustrations are planning aids, not observed power and not evidence that an analysis had a particular probability of detecting an effect.

In general, over-dispersion refers to greater variability in data than a model assumes. It can make standard errors and interval estimates unreliable if a model fails to account for that extra variability. The listed primary endpoint is binary, and the registry does not report an analysis model or dispersion estimate. Thus, there is no basis in the registry record to say whether over-dispersion was assessed or relevant to a fitted model.

A p-value, when reported, measures how compatible data are with a specified statistical model and null hypothesis; it is not the probability that a treatment works or that the null hypothesis is true. A p-value also does not measure clinical importance. No primary p-value, test, or model is reported. Without a result and its analysis details, readers cannot evaluate statistical evidence through a significance test.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Procedure 1")
n      <- c(10)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Procedure 1  10  6  60.0  26.2  87.8  31.3  83.2  30.8  83.3

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns the interpretation of multiple statistical tests or outcomes. If several procedures, endpoints, or subgroup analyses are tested, the chance of finding at least one apparently unusual result can rise unless the analysis addresses the number and purpose of tests. The registry lists one outcome measure and describes three procedures, but it reports no analyses. A multiplicity strategy, hierarchy of outcomes, or planned comparison approach is not reported in the registry record.

The registry lists zero analyses. This means no analysis result is available in the posted record; it does not establish which analyses may or may not have been conducted outside the registry. The statistical analysis plan, any interim analyses, and a sample-size justification are not reported in the registry record. No method for adjusting estimates or tests for multiplicity can therefore be attributed to the study.

Missing-data handling is also not reported. The primary endpoint description refers to participants who initiated Procedure 1 and completed the study, while its population description refers to all participants enrolled in Procedure 1. The record does not explain how these populations relate, whether every participant had an ascertainable injection status, or how an unknown status would be treated. It also gives no participant-flow account or sensitivity analysis for missing outcomes.

These omissions affect interpretation, rather than proving that a particular analysis was inappropriate. A clear analysis population and missing-data rule are needed to interpret an endpoint count or percentage. Since no primary result or analysis is posted, it is not possible to evaluate how the analysis addressed missing outcomes or multiple comparisons.

12. 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 5% reporting threshold.

For Procedure 1, the registry lists 10 participants at risk for serious adverse events and 0 affected. It also lists 10 at risk in the other-event category and 0 affected, with 0 deaths. No serious adverse event terms are listed. These are the safety counts reported in the registry record.

These figures are descriptive, not a comparison between procedures or between treatment and control groups. The study is listed as non-randomized and single-group, and the safety record provided does not include comparative estimates or uncertainty intervals. A count of 0 affected means no events were recorded in that listed category in the posted group; it does not establish that an event is impossible or that there is no risk.

The registry record does not explain the categories beyond serious events and other events, report event-level details, or provide a broader safety analysis. It also does not give the reason for termination. The safety counts cannot be used to infer that safety findings caused or did not cause termination.

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

The registry record identifies a focused primary question: whether participants in Procedure 1 receive a second XR-NTX injection 4 weeks after the first. It also describes three outpatient induction procedures and records safety counts for Procedure 1. These details clarify what the study set out to examine and what information is posted.

The record does not report the primary endpoint result. As a result, it does not establish how many participants received the second injection, what proportion did so, or how uncertain an estimate might be. It also does not report a statistical test or confidence interval for the endpoint. No conclusion about the observed primary outcome can be drawn from the endpoint wording itself.

The study design limits comparative interpretation. Non-randomized allocation and a single-group model do not provide a randomized basis for attributing differences to the procedures. The three procedure descriptions are not accompanied by reported procedure-specific results or a comparative analysis. The posted information therefore does not establish which procedure had a higher or lower rate of reaching the endpoint.

The safety counts show 0 serious adverse events, 0 events in the other-event category, and 0 deaths among the listed Procedure 1 group at risk. These counts describe the entries in the registry, not all possible risks or outcomes. The record does not provide event terms or uncertainty estimates that would support a broader safety conclusion.

The enrollment figure is 10, while the brief summary describes a plan to enroll 30. The record does not explain this difference or state why the trial was terminated. Neither the enrollment discrepancy nor the termination status identifies the reason for the study's status. Overall, the posted record supports a cautious account of the design and available counts, but not a claim about the primary result, efficacy, comparative benefit, or the cause of termination.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why a clear outcome definition and a reported analysis matter as much as a stated research question. The primary endpoint concerns receipt of a second injection at a specified follow-up time. Yet the endpoint description and population description use different wording about who is included: participants who initiated and completed Procedure 1 versus all participants enrolled in Procedure 1. Without a resolved denominator and outcome result, readers cannot interpret the endpoint as a rate.

The study also illustrates the distinction between a procedure description and a comparative design. Three procedures are described, but the registry lists non-randomized allocation and a single-group model. That distinction is essential: the presence of multiple procedures does not itself create a randomized comparison or justify a causal ranking. A design and analysis must support the contrast before comparative claims can be made.

Enrollment and planning figures also answer different questions. The record lists enrollment of 10 and separately describes a planned enrollment of 30. A planning target is not the observed enrollment, and a sample-size illustration is not evidence that a study was adequately powered or that an effect was detected. The posted record does not give a protocol-based justification or primary analysis results.

Finally, registry status and outcome reporting should be read separately. Termination is recorded, but its reason is not reported. The serious-event counts are also descriptive and do not supply the missing primary outcome. Together, these details show why readers need transparent participant flow, analysis populations, missing-data handling, and outcome estimates before drawing statistical conclusions from a clinical trial record.

15. 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 interpreting this study is the absence of a posted primary endpoint result or analysis. The registry describes the outcome but does not give an event count, percentage, confidence interval, or test result. The primary question therefore cannot be answered using the registry record alone.

The listed enrollment is 10, whereas the brief summary describes a plan to enroll 30. The registry does not explain the difference. It also does not explain why the study was terminated. These points limit understanding of recruitment and study conduct, but they do not establish a cause or imply an outcome.

The record describes three procedures while listing a single-group model and non-randomized allocation. It does not report how participants were allocated to procedures, whether procedure-specific outcome data exist, or whether a comparative analysis was conducted. Any comparison would require caution because the registry does not describe randomized assignment.

The endpoint's population wording is not fully aligned: the endpoint description refers to participants who initiated Procedure 1 and completed the study, while the population description refers to all participants enrolled in Procedure 1. The record does not report participant flow, the number with outcome data, or missing-data rules. The analysis population and denominator are therefore unclear.

Further limitations include the absence of a reported statistical analysis plan, sample-size justification, multiplicity approach, and interim-analysis information. The registry lists no analyses. The safety information is limited to the listed Procedure 1 counts and does not include serious-event terms or uncertainty estimates. These reporting gaps constrain interpretation; they do not, on their own, establish how the study was conducted beyond what the registry record states.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Buprenorphine as Adjunct to Outpatient Induction Onto Vivitrol — NCT03113409.
• Registry record last updated 2022-03-02; status last verified 2022-02.
• Results first posted 2022-03-02.
• 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.

19. Record Summary

NCT03113409 is a terminated outpatient study of buprenorphine-assisted induction onto XR-NTX for opioid-use disorder. The registry lists Phase 2 and Phase 3, non-randomized allocation, no masking, and a single-group model. It records enrollment of 10; the brief summary describes a planned enrollment of 30.

Three procedures are described, varying in induction duration and whether buprenorphine continues after the first XR-NTX injection. The primary endpoint concerns receipt of a second injection 4 weeks after the first and is specific to Procedure 1. Its observed result and statistical analysis are not reported in the registry record. The endpoint population wording is not fully consistent about whether it includes all enrollees or only participants who initiated and completed the procedure.

For Procedure 1, the registry lists 0 serious adverse events, 0 in the other-event category, and 0 deaths. The reason for termination, missing-data methods, and statistical analysis plan are not reported in the registry record.