Evaluating the Use of Sublingual Sufentanil in Patients With Suboxone Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Use of Sublingual Sufentanil in Patients With Suboxone Treatment (NCT04716413), a non-randomized phase 4 study. The primary outcome is Morphine Equivalence.

2. Clinical Question

The registry describes a question about postoperative pain management in ambulatory surgery patients taking Suboxone: whether adding sublingual sufentanil, Dsuvia, changes opioid use and related recovery outcomes compared with routine standard of care. The investigators’ stated hypothesis concerned improvement in postoperative pain management in the Post Anesthesia Care Unit (PACU). The registered primary outcome, however, was total morphine equivalence during the perioperative period, combining opioid use in the operating room and PACU.

This is a descriptive clinical question, not a randomized efficacy comparison. The allocation was non-randomized, and the record identifies no masking. Differences between the treatment and control groups could therefore reflect patient or care differences as well as the intervention. Since the primary endpoint has no posted analysis, the registry cannot answer whether the groups differed in morphine equivalence. The secondary outcomes concern discharge readiness, additional opioid use, time to first additional opioid, and adverse events, but the record does not report analyses of those outcomes either.

3. Trial Design

This was a Phase 4, parallel-model study registered as a case series. Its official title describes ambulatory surgery patients taking Suboxone, and the brief description states that investigators were testing a hypothesis about postoperative pain management in the PACU. The sponsor was Montefiore Medical Center. The registry records a start date of 2021-09-27 and a primary completion date of 2022-11-17. The current status is terminated; the reason for termination is not reported in the registry record.

The allocation is listed as non-randomized, and masking is listed as none. The registry identifies treatment and control arms, but these do not constitute a randomized, like-for-like comparison. The treatment arm is described as receiving Dsuvia 30mcg sublingually after induction but before the first incision. Post-operatively, the description specifies a second 30mcg dose if the pain rating is higher than 4 out of 10. The description then begins to describe a further decision 30 minutes after that second dose, but the text is truncated. The complete dosing pathway is therefore not reported in the registry record. The control arm is described as receiving routine standard of care, without further detail.

Enrollment is recorded as 3. That figure does not establish how many participants contributed data to any particular outcome. The primary outcome’s population field says data were not collected or aggregated, and there was no data analysis for the terminated study. The registry lists secondary outcomes concerning time to fit for PACU discharge, need for additional opioids following surgery, time to first additional opioid, and adverse events in the PACU and after PACU discharge. The record does not provide outcome estimates for these measures.

Because the study was non-randomized and had no masking, treatment decisions and outcome assessment may have been influenced by clinical circumstances or knowledge of treatment. General statistical interpretation of non-randomized studies therefore requires caution about confounding and measurement differences. Here, the absence of analyzed primary-outcome data is an additional, decisive limitation: the record supports describing the intended design and registered question, but not estimating a comparative treatment effect.

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

Analysis population for the primary outcome, as defined in the registry: Data was not collected/aggregated. As such there was no data analysis for this terminated 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.

Population: No participants were enrolled into the Control (Standard of Care) arm prior to study termination. As such, zero participants were identified in the corresponding categories for the Control (Standard of Care) arm.

6. Primary Endpoint

The registry lists the primary outcome as Morphine Equivalence, measured over During day of surgery.

The primary endpoint was morphine equivalence (MME) during the day of surgery. The registry defines it as the combined total opioid used intra-operatively and in the PACU. This endpoint is intended to express different opioid use in a common morphine-equivalent measure, allowing perioperative opioid exposure to be considered as a single quantity rather than as separate drug amounts. That is a general rationale for using morphine equivalence; the registry does not report the conversion method used in this study.

In this clinical context, the endpoint was relevant to the stated question about perioperative opioid use among ambulatory surgery patients taking Suboxone. It covered both opioid use during the operation and use in the recovery unit, rather than pain ratings alone. The registry specifies the timeframe as the day of surgery.

Crucially, the record states that the primary-outcome data were not collected or aggregated and that no data analysis was performed for the terminated study. It gives no group-level MME values, participant-level results, estimate of a difference, or uncertainty interval. The endpoint’s definition therefore explains what the study intended to measure, but there is no posted result from which to judge the amount of opioid used or the precision of a comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the study as a parallel-model, non-randomized Phase 4 case series with no masking. It records treatment and control arms, but its own design description does not support treating them as exchangeable groups. The primary endpoint was defined as total morphine equivalence from intra-operative and PACU opioid use during the day of surgery. The registry reports no collected or aggregated data for that endpoint and no data analysis for the terminated study.

What does non-randomized allocation mean?

As a general statistical concept, random allocation aims to make groups comparable, on average, with respect to measured and unmeasured characteristics. When allocation is non-randomized, the reasons a person receives one arm rather than another can also relate to prognosis or care. This can create confounding: an observed difference may reflect those factors, the intervention, or both. A statistical adjustment can sometimes address measured differences, but it cannot automatically remove bias from factors that were not measured or modeled. The registry does not report an adjustment plan or adjusted estimates.

The control arm is described only as routine standard of care. The treatment description includes a first sublingual dose after induction and before the first incision, followed by a conditional post-operative dose. The recorded wording about what might happen after the second dose is incomplete. Without a complete treatment description and more detail about routine care, the intervention contrast cannot be fully reconstructed from the registry record.

What would a confidence interval tell a reader?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval; an interval’s location relative to a no-difference value can help assess compatibility with different effects. It does not address design bias, outcome measurement problems, or whether a difference is clinically important. No confidence interval for MME or the listed secondary outcomes is reported in the registry record, because the primary data were not collected or analyzed and no outcome analyses are posted.

How should the planning calculations be understood?

The registry’s planning assumptions describe illustrations based on an observed effect, not the original trial design. The stated framework uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the target effect is described as a fraction of the observed effect. For time-to-event outcomes, the stated format is a total number of events, while other outcomes are expressed as participants per arm. These are general sample-size planning conventions, not results about participants in this study and not observed power. A planning calculation does not show that a study had a particular probability of detecting an effect after the fact.

Interpreting such illustrations ordinarily requires knowing the outcome estimate used, its variability, the assumed allocation, and the design assumptions. The registry record does not provide a primary-outcome analysis or an MME estimate to interpret, and it does not report the study’s own sample-size justification. The planning assumptions therefore should not be read as proof that the study was designed to detect a specified clinical difference. No numerical planning estimate is stated in the registry entries described for this account.

Why does dispersion matter in general?

For continuous outcomes such as a quantity expressed in morphine equivalents, the spread of participant values matters because it affects the precision of a group mean and the information available for comparing groups. For count outcomes, variation may exceed what a simple statistical model assumes; this is called over-dispersion. In general, ignoring over-dispersion can make uncertainty appear smaller than it is. Time-to-event outcomes require attention to event timing and censoring, while binary outcomes require clear event counts and denominators. These concepts explain why an outcome’s distribution and analysis method matter, but the registry does not report distributional summaries, variance estimates, event-time data, or model choices for the outcomes in this study.

What analyses are documented?

The registry reports no analyses. It does not provide an estimate, standard error, confidence interval, p-value, covariate-adjusted model, or a prespecified statistical analysis plan. The absence of an analysis means there is no sponsor analysis to compare with a simple recalculation from summary statistics. Any general discussion of statistical methods is therefore explanatory rather than a description of methods actually applied to these trial outcomes.

For a non-randomized study, a suitable analysis would need to be interpreted alongside how the arms were formed, what baseline information was available, how outcomes were measured, and which participants contributed data. Those details are not reported in the registry record. In this record, the most defensible statistical reading is not to infer an effect from design descriptions, enrollment, or safety counts, but to note that no primary-outcome estimate is available.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies morphine equivalence as the primary outcome and lists secondary outcomes addressing PACU discharge readiness, additional opioid use, time to first additional opioid, and adverse events during and after PACU care. It does not report analyses for these outcomes. No statistical analysis plan, hierarchy among secondary outcomes, or multiplicity adjustment is reported in the registry record.

Multiplicity is a general concern when several outcomes or comparisons are examined: the chance of at least one apparently unusual result can increase when many tests are conducted. A prespecified primary outcome and a stated testing strategy help readers understand which results are confirmatory and which are exploratory. Here, the primary endpoint is defined, but no outcome analysis is posted; the record does not say how multiple outcomes would have been handled if analyses had been conducted.

The primary outcome description explicitly states that data were not collected or aggregated. The registry does not report missingness by arm or outcome, reasons for missing observations, imputation, exclusions, or sensitivity analyses. It also does not describe analysis populations such as an intention-to-treat or per-protocol population. Consequently, it is not possible to determine whether missing data arose from non-collection, incomplete follow-up, or another process beyond the primary outcome statement. No participant flow or outcome-specific denominators are reported in the registry record.

These omissions matter because estimates can depend on which observations are included and how unavailable values are handled. In general, imputation cannot recover information reliably without assumptions about the missing-data process, and complete-case analyses can be biased when missingness relates to outcome or treatment. Those are general considerations, not claims about what happened in this study. The registry provides no basis for evaluating missing-data assumptions or multiplicity control.

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 adverse-event entries show 0 serious adverse events and 0 deaths in the treatment group, with 3 at risk. For the control group, the at-risk count is 0, the serious-event count is 0, the other-event count is 0, and the death count is 0. The treatment group also has 0 other adverse events recorded. These are registry entries, not evidence of equivalent safety between arms.

The at-risk count is essential context for interpreting a zero event count. A recorded zero among participants at risk means no event was entered for that group in the registry’s adverse-event summary; it does not establish that an event is impossible or that the underlying risk is zero. The control group’s at-risk count of 0 means there is no exposed control group represented in these safety entries for a comparison. The record therefore does not support a relative safety estimate.

These counts are also limited by the small enrollment entry, termination status, and absence of reported outcome analysis. The registry does not provide event definitions, observation duration for each participant, or detailed safety assessment procedures. The listed secondary outcomes include adverse events in the PACU and after discharge from PACU, but no analyzed results for those measures are reported. The serious-event figures should be read narrowly as recorded counts, not as a comprehensive or comparative safety conclusion.

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

The registry establishes that investigators planned to study sublingual sufentanil in ambulatory surgery patients taking Suboxone and registered perioperative morphine equivalence as the primary outcome. It also records the intended treatment and routine-care control arms, several secondary outcomes, enrollment of 3, and a terminated status. These registry entries describe the study question and its recorded structure.

They do not establish whether Dsuvia changed perioperative opioid use, pain management, discharge readiness, or the need for additional opioids. The primary endpoint was not collected or aggregated, and no data analysis was performed for the terminated study. The registry does not report comparative estimates or uncertainty intervals for the primary or secondary outcomes. Without those results, no direction, magnitude, or precision of a treatment contrast can be inferred.

The safety summary records no serious adverse events or deaths in the treatment group, but the control group has no participants at risk recorded. That pattern does not allow a meaningful between-arm safety comparison. Zero recorded events should not be converted into a claim of no risk, especially when the record does not supply the context needed to evaluate event surveillance or follow-up.

Even if comparative outcomes were available, the non-randomized allocation and lack of masking would limit causal interpretation. General differences between groups, clinical decisions, or outcome assessment could contribute to an observed contrast. The record does not report methods to address such concerns. The appropriate conclusion is therefore about the registry evidence, not about treatment benefit or harm: the study registered a clinical question but posted no analyzed primary-outcome result capable of answering it.

13. Why This Trial Matters Statistically

This record matters statistically because it illustrates the difference between a registered research question and evidence that can answer it. A primary endpoint can be clearly defined—in this case, perioperative morphine equivalence combining intra-operative and PACU opioid use—without a result being available. The registry expressly states that the data were not collected or aggregated and that no analysis was performed. A careful reader should distinguish endpoint specification from endpoint evidence.

It also demonstrates why study design belongs in any interpretation. Non-randomized allocation and no masking do not automatically make a study uninformative, but they require attention to how groups were formed and whether clinical or measurement differences could explain an apparent contrast. The registry does not report an adjusted analysis or enough detail to assess those possibilities. Here, the absence of analyzed outcomes means that even a cautious comparative estimate is unavailable.

The record also shows why denominators matter when reading safety counts. The treatment group has an at-risk count, while the control group has none recorded. Zero event entries across those groups cannot be treated as evidence of equal risk. Counts need exposure context and comparable follow-up to support a meaningful contrast.

Finally, planning calculations and observed findings answer different questions. A sample-size illustration is a planning aid under stated assumptions; it is not a result, a guarantee of precision, or observed power. This distinction is important when a record has no primary-outcome analysis. The statistical value of the registry is thus transparency about the intended endpoint, design, and lack of analysis, rather than a quantitative estimate of the intervention’s effect.

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 most direct limitation is the absence of primary-outcome data. The registry says MME data were not collected or aggregated and that the terminated study had no data analysis. This prevents estimation of the primary outcome and leaves no statistical uncertainty to assess. The record also does not report outcome results for the listed secondary measures.

The study was non-randomized and unmasked. The control arm is described only as routine standard of care, and the record does not explain how participants entered either arm or whether the groups differed at baseline. It does not report adjustment methods, making it impossible to evaluate how potential confounding would have been addressed. The enrollment entry is 3, but the record does not show outcome-specific denominators or participant flow.

The treatment description is incomplete after its account of conditional post-operative dosing: the text ends while describing what may happen 30 minutes after a second dose. The full protocol for subsequent dosing is therefore not reported in the registry record. The registry also does not specify the MME conversion method, provide detailed outcome-assessment procedures, or describe how adverse events were defined and followed.

The status is terminated, but the reason for termination is not reported in the registry record. The record does not give a sample-size justification, statistical analysis plan, multiplicity approach, missing-data method, or analysis-population definition. These limitations restrict both clinical interpretation and assessment of statistical validity. They should not be filled in by assuming a reason for termination or a method that the registry does not document.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Use of Sublingual Sufentanil in Patients With Suboxone Treatment — NCT04716413.
• Registry record last updated 2023-07-19; status last verified 2023-06.
• Results first posted 2023-07-19.
• 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

NCT04716413 is a Phase 4, parallel-model, non-randomized case series sponsored by Montefiore Medical Center. It concerns ambulatory surgery patients taking Suboxone and evaluates sublingual sufentanil, Dsuvia, against routine standard of care. The registry records no masking, enrollment of 3, and terminated status. The primary endpoint is perioperative morphine equivalence during the day of surgery, defined as combined intra-operative and PACU opioid use.

The registry states that primary-outcome data were not collected or aggregated and that no data analysis was performed. It lists secondary outcomes involving PACU discharge, additional opioid use, and adverse events, but does not report analyzed results for them. The serious adverse-event summary records 0 serious events and 0 deaths in the treatment group, with 3 at risk; the control group has 0 at risk. The reason for termination and the study’s own sample-size justification are not reported in the registry record.