Nalrexone Facilitated Discontinuation of Buprenorphine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nalrexone Facilitated Discontinuation of Buprenorphine (NCT01895036), a na phase 1, phase 2 study. The primary outcome is Successful Discontinuation of Buprenorphine.

2. Clinical Question

The registry summary presents a rationale for studying naltrexone during buprenorphine discontinuation. It describes the possibility that discomfort during tapering may relate to changes in kappa-opioid receptor activity, and proposes naltrexone as a candidate for extending kappa blockade. This is the rationale recorded for the investigation, not evidence that the intervention changed the primary outcome. With no comparator and no posted primary result, the record cannot establish whether the intervention affected the likelihood of successful discontinuation.

3. Trial Design

This is a completed Phase 1 and Phase 2 study, classified as a single-group trial. The registry lists enrollment of 6 and identifies New York State Psychiatric Institute as the sponsor. The listed start is 2011-02, and primary completion is 2013-09. Allocation is recorded as not applicable, and masking is listed as none. There is no randomized or masked comparison described in the record.

Participants received naltrexone. The arm description says that oral naltrexone was titrated on a mixed inpatient and outpatient basis, followed by administration of Vivitrol four days after the first naltrexone dose. Further details about the titration schedule, treatment duration, or implementation are not reported in the registry record.

The primary outcome is the number of individuals who successfully discontinued buprenorphine during the inpatient phase and through follow-up. The listed timeframe is 7 weeks. The record describes the endpoint as a count of participants, rather than a continuous measurement or a time-to-event estimate. It does not report the observed count, an effect estimate, or an uncertainty interval for this outcome.

Because the design has no control group, its primary outcome can describe what happened among participants in the study but cannot by itself distinguish an intervention effect from other explanations. The record does not report a sample-size justification, a planned statistical analysis, or details of an analysis population. The posted registry record marks the study completed, but completion status does not supply the missing primary outcome result.

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

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 Successful Discontinuation of Buprenorphine, measured over 7 weeks.

The primary endpoint counts participants who successfully discontinued buprenorphine during the inpatient phase and through follow-up. The registry lists the outcome timeframe as 7 weeks and the measurement unit as participants. In practical terms, the endpoint is a binary status for each participant—successful discontinuation or not—reported as a count rather than as a change in a continuous scale.

This kind of endpoint is useful when the clinical question concerns whether a defined milestone was reached. A count can make the outcome directly interpretable, but its meaning depends on how “successfully discontinuing” was defined and assessed. The registry description does not give an operational definition, criteria for handling partial discontinuation, or details about how outcome status was verified. Those details are not reported in the registry record.

The endpoint is intended to capture discontinuation during the inpatient phase and through follow-up, not simply an initial reduction or a short-term response. However, the record does not report the observed number of successful discontinuations or a statistical estimate of the probability of success. As a result, the endpoint definition is available, but the primary result itself cannot be interpreted from the posted registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the trial as single group, with allocation not applicable and no masking. This means the record describes participants receiving the intervention without a concurrent control group. In general, a controlled comparison helps distinguish differences associated with treatment assignment from differences that could arise because groups started with different characteristics or experienced different circumstances. A single-group study does not provide that comparison, so its results are descriptive of the enrolled group.

What does the primary outcome measure?

The endpoint is a count of participants who successfully discontinued buprenorphine during the inpatient phase and through follow-up. The listed timeframe is 7 weeks. A participant-level outcome of this kind can be represented as a binary status: the event of interest either occurred or did not occur. The registry identifies the outcome as a participant count, but the operational criteria for success are not reported in the registry record. Without those criteria, readers cannot assess precisely how borderline or incomplete discontinuation was classified.

Why does the missing outcome result matter?

For a binary outcome, interpretation ordinarily begins with the event count and the number of participants assessed. Those quantities allow an estimate of the event proportion and an assessment of its precision. The primary outcome count is not reported in this record, and the number assessed for the primary endpoint is also not reported. No proportion, confidence interval, or hypothesis test can therefore be interpreted from the posted results. Enrollment of 6 is not a substitute for the number with an observed outcome.

In general, a confidence interval conveys the uncertainty around an estimated quantity. It reflects both the observed data and the statistical method used to analyze them. A small study generally yields less precise estimates than a larger study when other features are comparable, especially for binary outcomes that may occur infrequently. This is a general statistical point, not a calculated precision statement about this trial: the primary result needed to quantify precision is absent from the record.

What can a single-group result show?

If a primary outcome count were reported, it could describe how many participants in the study group met the endpoint under the study conditions. It would not, by itself, estimate the causal effect of naltrexone compared with no intervention or another treatment. Without a concurrent comparator, observed outcomes may reflect factors beyond the intervention, including participant characteristics and the circumstances of care. This limitation applies to interpretation of the design; it does not mean that a particular alternative explanation occurred.

The registry does not report a prespecified statistical analysis, an effect estimate, or a p-value for the primary endpoint. A p-value, in general, summarizes how compatible data are with a specified statistical null model, under the assumptions of the test. It is not a measure of clinical importance and does not establish causation. Since no primary test result or analysis method is reported, there is no p-value to interpret for this study.

How should planning calculations be understood?

The record describes a sample-size planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It also defines the target effect as a stated fraction of the observed effect. These are planning assumptions, not a description of this trial’s single-group design: the trial does not have two allocated arms. The registry record does not report the trial’s own sample-size justification, and planning illustrations are not observed power. No planning value should be read as evidence of the primary result.

For count outcomes, statistical methods must also reflect the structure of the data. In general, over-dispersion occurs when outcome variability is greater than a model assumes; ignoring it can make uncertainty appear too small. That issue is not established as relevant to this particular endpoint from the posted information. The endpoint is described as a participant count, and the registry record does not report a count model, dispersion assessment, or alternative model.

There is no time-to-event analysis reported. Although the endpoint covers a period of follow-up, the registry describes it as a count of participants who successfully discontinued, rather than as the time until discontinuation. The analysis method, handling of follow-up time, and any censoring rules are not reported in the registry record. A timeframe alone does not imply a time-to-event analysis.

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("Naltrexone")
n      <- c(6)
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  Naltrexone  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and records zero analyses. This describes what is listed in the registry record; it does not establish that no analyses were conducted outside the record. No multiplicity procedure, hierarchy of hypotheses, or adjustment for multiple testing is reported in the registry record. Multiplicity matters in general when several outcomes or hypotheses are tested, because repeated testing can increase the chance of a misleading positive finding. The posted information is insufficient to determine whether that concern was addressed in the study’s analysis.

Missing-data handling is not reported in the registry record. The primary endpoint result and the number of participants with an observed endpoint are also not reported. Therefore, the record does not show whether all enrolled participants contributed to the endpoint, how missing assessments were treated, or whether any sensitivity analyses were used. These omissions prevent assessment of possible bias from incomplete outcome data.

Analysis populations are not described. The record does not state whether the primary analysis included everyone enrolled, only participants who started the intervention, or another defined group. It also does not report protocol-deviation rules or a method for handling participants who did not complete the intended intervention. These details are not reported in the registry record, so no particular analysis population should be assumed.

The registry’s sample-size illustration is explicitly a planning exercise and is not the trial’s own design justification. The record does not report an analysis plan or explain whether any interim analyses were planned or conducted. Those matters are not reported in the registry record.

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 0% reporting threshold.

For the naltrexone group, the registry reports 6 participants at risk for serious adverse events and 0 affected. It reports 6 at risk for other adverse events and 0 affected. Deaths are reported as 0. No serious adverse-event terms are listed. These are the safety counts in the posted registry record.

“At risk” refers to the group represented in the registry’s safety reporting; it should not be confused with the number known to have completed every part of follow-up. The record does not give additional details about the safety observation period, event collection methods, or whether the counts include events regardless of attribution. Those details are not reported in the registry record.

Zero reported events in a study group does not prove that the intervention has no risk. In general, a study with limited enrollment has limited ability to detect uncommon events, and a zero count can coexist with uncertainty about the underlying event frequency. No rate or confidence interval is reported for these safety outcomes, and none can be interpreted from the posted counts alone. The serious-event figures should be read as descriptive observations, not as a comprehensive estimate of safety.

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

The registry record establishes that a completed single-group study evaluated naltrexone in the context of buprenorphine discontinuation. It specifies oral naltrexone titration on a mixed inpatient and outpatient basis, followed by Vivitrol four days after the first naltrexone dose. The primary outcome was successful discontinuation during the inpatient phase and through follow-up, with a listed timeframe of 7 weeks.

The central result needed to answer the study’s primary question—the number of participants who successfully discontinued buprenorphine—is not reported in the registry record. Thus, the posted information does not show whether participants reached that endpoint, how often they did so, or how precisely any observed outcome was estimated. The study’s completed status does not fill this gap.

The design also limits causal interpretation. With no comparator group, the record cannot show what would have happened under an alternative approach or without the study intervention. Any reported single-group outcome would describe the study participants, rather than establish that the intervention caused the outcome. In this record, the primary outcome itself is not available for that descriptive assessment.

The safety entries show zero participants affected by serious adverse events, zero affected by other adverse events, and zero deaths in the reported group. These observations are useful as a description of the registry entries, but they cannot establish the absence of risk or characterize uncommon adverse events with precision.

The registry summary offers a biological rationale involving opioid receptor activity and the potential role of naltrexone during discontinuation. A rationale motivates a research question; it is not a study finding. The posted information therefore supports conclusions about what was planned and how the study was classified, but not a conclusion about whether naltrexone facilitated discontinuation.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between a registered research question and an interpretable result. The registry identifies a direct participant-level endpoint—successful buprenorphine discontinuation—and a defined timeframe of 7 weeks. Yet the endpoint count is not reported. Without that result, readers cannot estimate the observed outcome, quantify its precision, or evaluate how it relates to the study’s stated rationale.

The single-group design is another important feature. It can describe outcomes among participants who receive an intervention, but it does not supply the counterfactual comparison needed to estimate what would have happened to similar participants under another approach. This distinction helps prevent descriptive outcomes from being mistaken for causal treatment effects.

The record also makes clear why outcome definitions and analysis details matter. The endpoint is named, but operational success criteria, missing-data handling, and analysis populations are not reported in the registry record. Those elements affect which participants and events contribute to an estimate and how that estimate should be interpreted. Their absence limits reproducibility and critical appraisal.

Finally, zero reported adverse-event counts are not a substitute for a complete safety assessment, particularly when enrollment is 6. The counts describe what the registry reports; they do not establish that rare risks are absent. Together, these features make the record a useful example of how design, endpoint reporting, and uncertainty determine what can—and cannot—be concluded 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 the study is that the primary outcome result is not reported in the registry record. The observed count of successful discontinuations, the number assessed, and any uncertainty estimate are unavailable. Without these, the central research question cannot be answered from the posted results.

The study is single group, with no comparator and no masking. This limits the ability to distinguish intervention-related outcomes from other influences and does not support a controlled treatment contrast. The record does not report further details about eligibility, participant characteristics, or the criteria used to determine successful discontinuation. The enrolled population’s representativeness therefore cannot be assessed from the posted information.

Enrollment is 6, which leaves limited information for describing variation in outcomes or uncommon adverse events. This observation is about the amount of information in the study, not a calculation of statistical power. The trial’s own sample-size rationale is not reported in the registry record.

The intervention description provides the broad sequence of oral titration and later Vivitrol administration, but further dosing and implementation details are not reported. The record also does not report missing-data methods, analysis populations, a statistical analysis plan, or the definition of the primary endpoint beyond the outcome description. These gaps constrain reproducibility and make it difficult to evaluate the handling of incomplete follow-up or deviations from the intervention.

Although safety counts are posted, the record does not provide additional information about event ascertainment or the safety observation period. Accordingly, the absence of reported events should not be interpreted as proof of no risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nalrexone Facilitated Discontinuation of Buprenorphine — NCT01895036.
• Registry record last updated 2018-06-15; status last verified 2018-06.
• Results first posted 2017-09-06.
• 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

The registry record describes a completed Phase 1 and Phase 2, single-group study sponsored by New York State Psychiatric Institute. Enrollment is listed as 6. The study evaluated naltrexone, with oral titration on a mixed inpatient and outpatient basis followed by Vivitrol four days after the first dose. Allocation is not applicable, and masking is listed as none.

The primary outcome was the number of participants who successfully discontinued buprenorphine during the inpatient phase and through follow-up, with a timeframe of 7 weeks. The primary outcome result is not reported in the registry record. The posted safety counts are 0 affected by serious adverse events, 0 affected by other adverse events, and 0 deaths in the naltrexone group. No serious-event terms are listed. Missing-data handling, analysis populations, and the study’s own sample-size justification are not reported in the registry record.