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 Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age (NCT05391555), a na phase 2, phase 3 study. The primary outcome is Area Under the Time Concentration Curve (AUROC ).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05391555 |
| Phase | Phase 2, Phase 3 |
| Condition | Opioid Toxicity, Pupillary Miosis, Respiratory Depression |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
Subjects aged 40–60. The registry record describes a planned study in this age group; detailed participant characteristics are not reported in the registry record.
Intervention
Remifentanil hydrochloride was infused, with pupillary measures obtained using pupillometry. The reported schedule included a baseline measurement and repeated measurements during infusion and recovery.
Comparator
There was no separate control arm. The primary measure compares PUAL classifications at zero-to-moderate opioid concentration (<1.8 ng/mL) with classifications at high-toxic opioid concentration (>2.5 ng/mL).
Primary question
How well does PUAL distinguish the specified opioid concentration categories among subjects aged 40–60, as assessed by the area under a receiver operating characteristic curve?
The study addresses whether a pupillary measure can discriminate between opioid concentration categories in this age group. Its background rationale is that prior investigation in subjects aged 20–40 found loss of PUAL to be a sensitive, discriminative indicator of opioid toxicity and respiratory depression, while population data indicate that pupil size and PUAL decline slightly with age. The registry describes the present study as exploring whether PUAL is a sensitive indicator of opioid exposure and respiratory depression in the older group. That rationale is not itself evidence of the measure’s performance in this study.
The design is not a comparison of remifentanil with a different treatment or with an untreated control group. Instead, the endpoint uses concentration categories as the states to be distinguished and relates those categories to pupillary measurements collected over time. The registry record does not report the numerical AUROC, its confidence interval, or other performance estimates. Consequently, the clinical question is identifiable, but the posted record does not establish how accurately PUAL distinguished the categories in the enrolled participants.
3. Trial Design
This is a completed, single-group study sponsored by the University of California, San Francisco. The registry lists Phase 2 and Phase 3, enrollment of 10, and an allocation value of NA. Masking is listed as none, and the model is single group. These characteristics describe a study without a randomized, masked, parallel control arm. The listed phases do not supply additional detail about how the study was designed or analyzed.
Participants underwent a 10-minute remifentanil infusion followed by a 25-minute recovery period. Pupillary measures were taken at baseline and every 2.5 minutes during the infusion and recovery. The interventions listed are remifentanil hydrochloride and pupillometry measurement. The registry record does not report further details about the administration protocol, measurement device specifications, or participant eligibility beyond the age range in the title and study description.
The primary outcome is described as an AUROC for dichotomous classification of PUAL at zero-to-moderate opioid concentration (<1.8 ng/mL) versus high-toxic opioid concentration (>2.5 ng/mL). Thus, the primary question concerns discrimination across exposure categories, not a between-group treatment effect. The registry does not report a comparison arm, a randomization procedure, or a masking procedure beyond the listed values.
The study start date is 2022-10-01, the primary completion date is 2023-06-03, and status is completed. Although an enrollment count and an outcome definition are recorded, the registry record does not report a numerical primary outcome result or an analysis estimate. The sample-size justification, detailed statistical analysis plan, interim analyses, and analysis populations are not reported in the registry record. The recorded enrollment should therefore be read as the study enrollment, not as evidence about precision or statistical power.
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
| Stage | Remifentanil Infusion and Recovery |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
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 | Remifentanil Infusion and Recovery |
|---|---|---|
| Participants analysed | 10 | |
| Age, Customized: Age 40-60 years | Participants | 10 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 5 |
| Race/Ethnicity, Customized: White European | Participants | 4 |
| Race/Ethnicity, Customized: Asian/Pacific Islander | Participants | 3 |
| Race/Ethnicity, Customized: Black | Participants | 1 |
| Race/Ethnicity, Customized: Latinx | Participants | 2 |
| Region of Enrollment: United States | Participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Time Concentration Curve (AUROC ), measured over Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Probability |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is labeled Area Under the Time Concentration Curve (AUROC), with probability as its unit and a 95% Confidence Interval as its dispersion measure. Its description identifies a receiver operating characteristic curve, constructed using PUAL as a dichotomous classifier for zero-to-moderate opioid concentration (<1.8 ng/mL) versus high-toxic opioid concentration (>2.5 ng/mL). Despite the wording of the title, the description defines the endpoint as an area under a receiver operating characteristic curve, rather than an area under a concentration-time curve.
In general, a receiver operating characteristic curve describes how a classifier separates two states as its decision threshold varies. Its area summarizes discrimination across those thresholds. In general, an AUROC closer to the value associated with no discrimination indicates less separation, while a larger value indicates stronger ranking discrimination; interpretation depends on how the states and direction of classification are defined. The endpoint can therefore address whether PUAL distinguishes the concentration categories, but it does not by itself quantify a treatment effect or establish clinical usefulness.
The registry specifies a 95% confidence interval as the uncertainty measure, but it does not report the AUROC estimate or interval limits. It also does not report the operational PUAL threshold, details of how repeated observations were handled, or the analysis population. Without those results and analysis details, the intended endpoint is clear, but its observed value and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record defines a discrimination question: whether PUAL separates observations associated with the specified lower and higher opioid concentration categories. It does not provide a numerical AUROC or confidence interval. There is therefore no reported estimate from which to describe the observed degree of discrimination or its precision. The absence of a reported result should not be interpreted as evidence for either strong or weak performance.
In general, an AUROC is a summary of classification discrimination across possible thresholds. A confidence interval conveys uncertainty around an estimate under the assumptions of the analysis. A narrow interval would generally indicate greater precision than a wide interval, while an interval spanning values associated with materially different levels of discrimination can leave interpretation uncertain. Those general principles cannot be applied to characterize this study’s result because neither the estimate nor the interval limits are reported in the registry record.
The registered endpoint compares categories defined by concentration: zero-to-moderate concentration is stated as <1.8 ng/mL, and high-toxic concentration as >2.5 ng/mL. The description does not define what happens to observations between those thresholds, nor does it state how the dichotomous PUAL classification threshold was selected. Those details matter for understanding exactly which observations contribute to the discrimination estimate and how readily the classifier might be reproduced. They are not reported in the registry record.
The design is single group and has no like-for-like control arm. That is consistent with an endpoint focused on distinguishing exposure categories rather than estimating a randomized treatment contrast. It also means the primary endpoint, as described, cannot by itself isolate a causal effect of remifentanil on PUAL from other changes that could occur during infusion and recovery. The registry does not report a causal analysis or an analysis adjusting for other factors.
The registry lists enrollment of 10. That count alone does not tell readers how many observations fell into each concentration category, how many measurements were usable, or how the repeated measurements from a participant were treated statistically. Those details are not reported in the registry record. Repeated measurements can contribute information, but measurements from the same person are not necessarily independent; an analysis that treats them as independent when they are correlated can understate uncertainty. This is a general statistical consideration, not a claim about the analysis used in this study.
Overall, the record makes the intended question and measurement schedule understandable but does not support a conclusion about the observed accuracy or precision of PUAL. No numerical primary result, confidence interval limits, or analysis details are reported. The study’s stated rationale and endpoint definition should therefore be distinguished from empirical evidence about the outcome.
9. Statistical Methods Explained
The endpoint uses a receiver operating characteristic (ROC) approach. In general, ROC methods assess a classifier’s ability to distinguish observations belonging to two defined states. Here, those states are the registry’s zero-to-moderate opioid concentration category (<1.8 ng/mL) and high-toxic concentration category (>2.5 ng/mL). PUAL is the pupillary measure used for classification. The record identifies the endpoint as an AUROC and gives probability as its unit.
What does an AUROC represent?
In general, the ROC curve is formed by considering classification performance across possible decision thresholds. The area under that curve condenses the curve into a single discrimination summary. One common interpretation is the chance that a randomly selected observation from one state receives a more positive score than a randomly selected observation from the other state, subject to the chosen score direction and state coding. This interpretation explains why AUROC is useful when a question concerns separation rather than a single fixed operating threshold. It does not state the result of this study: the registry record reports no numerical AUROC.
The curve summarizes discrimination, not every practical aspect of a classifier. In general, it does not alone specify a threshold that would be used in practice, nor does it directly describe the consequences of false-positive and false-negative classifications. Those issues require additional information about the decision context, thresholds, and the relative importance of classification errors. The registry describes PUAL as a dichotomous classifier but does not report its threshold or other operating characteristics.
Why define exposure categories?
A dichotomous classification requires states to be specified. The registry defines the comparison as zero-to-moderate opioid concentration (<1.8 ng/mL) versus high-toxic opioid concentration (>2.5 ng/mL). Defining categories makes the discrimination question concrete, but the record does not say how observations between those limits were handled. Nor does it report whether the concentration values were assessed at every pupillary measurement or how the exposure and pupillary timing were paired. These are details needed to reproduce the analysis and judge how its population of observations was constructed.
In general, category definitions affect the interpretation and applicability of an AUROC. A result for two selected categories describes separation between those categories as defined; it does not automatically describe performance for every concentration or every clinical setting. This is a general point about classification analyses, not a claim that the category choices were inappropriate in this study.
What does the confidence interval add?
The endpoint lists a 95% confidence interval as its dispersion measure. In general, a confidence interval represents uncertainty around an estimate under the statistical model and sampling assumptions used. It is not a guarantee that the true value lies within the particular interval, and its width depends on the information available and the method used to calculate it. For an AUROC, the interval helps readers judge how precisely discrimination has been estimated. The interval limits and the method used to calculate them are not reported in the registry record, so this study’s precision cannot be evaluated from the posted result.
The repeated schedule is relevant to uncertainty. Measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period. In general, repeated measurements on the same participant may be correlated, because measurements from one person can share characteristics. Analyses need to account appropriately for that dependence when estimating uncertainty. The registry record does not explain whether the AUROC was calculated from individual measurements, participant-level summaries, or another unit of analysis, and it does not describe a method for handling repeated observations.
What does a single-group design imply for this endpoint?
The model is listed as single group, allocation is NA, and masking is listed as none. The endpoint compares concentration categories rather than treatment arms, so it is not a randomized between-treatment contrast. In general, a discrimination estimate can describe how a measure classifies states in the analyzed data, but it does not establish that the measure itself causes a change in an outcome. Nor does an AUROC alone establish that use of the measure improves decisions. The registry does not report an analysis intended to estimate such effects.
The registry lists enrollment of 10, but does not report how many observations belonged to each concentration category or how many were included in the endpoint analysis. In general, sparse data in either state can make an estimate less stable. The enrolled count should not be treated as a direct description of the number of independent classification observations, particularly when repeated measures may be present. No category counts or analysis sample sizes are reported in the registry record.
How should planning calculations be read?
General planning calculations are not the same as observed results or observed power. The planning assumptions recorded for this trial describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. They are explicitly described as a planning illustration computed from the observed effect, not as the trial’s own design. The record also distinguishes participant-per-arm planning quantities from total event quantities for time-to-event settings. Those assumptions do not turn this single-group study into a two-arm trial, and a planning illustration should not be read as an observed study outcome.
The numerical planning outputs and a numerical observed effect are not reported in the registry record. Therefore no planning quantity can be interpreted as a study-specific sample-size justification, and none can substitute for the missing AUROC estimate and confidence interval. In general, a sample-size calculation depends on assumptions about the target effect, variability, error rates, design, and analysis. If those assumptions differ from the actual data structure, the calculation may not describe the precision achieved.
Finally, the listed phase labels, completion status, and outcome definition do not disclose the full statistical methods. The analysis plan, handling of missing observations, multiplicity strategy, confidence-interval method, and analysis population are not reported in the registry record. General explanations of ROC analysis and uncertainty should not be mistaken for confirmation of which procedures the investigators used.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one primary outcome measure, but does not report the number of hypotheses tested or a multiplicity strategy. Multiplicity arises in general when several outcomes, time points, subgroups, or analyses are examined and statistical conclusions are drawn across them. If multiple comparisons are made, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. This is a general concern, not evidence that a particular multiplicity problem occurred in this study.
The schedule includes baseline and repeated pupillary measurements during infusion and recovery. The record does not state whether each time point was analyzed separately, combined in a prespecified way, or used only to construct the registered AUROC. It also does not say whether subgroup analyses or additional endpoints were considered. A single registered primary outcome does not establish that only one analysis was performed; the registry reports no analyses for the outcome.
Missing-data handling is not reported in the registry record. It does not state whether any measurements or participants had missing data, how missing observations were handled, or whether the endpoint analysis required complete measurement sequences. The enrollment count does not establish the number of observations contributing to the endpoint. In general, missingness can affect both the data available for analysis and the interpretation of estimates, especially when missingness is related to participant or measurement characteristics.
The analysis population is also not reported in the registry record. There is no description of whether the endpoint used all enrolled participants, a subset with usable measurements, or another defined group. The analysis plan, treatment of repeated measurements, and any sensitivity analyses are not reported. These omissions limit assessment of whether the analysis matches the stated endpoint and how robust any result would be; no numerical endpoint result is available to evaluate.
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 |
|---|---|---|---|
| Remifentanil Infusion and Recovery | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Remifentanil Infusion and Recovery | 0 of 10 |
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 |
|---|---|
| Remifentanil Infusion and Recovery | 0 of 10 |
The registry lists one group, Remifentanil Infusion and Recovery, with 10 participants at risk for serious adverse events and 0 affected. It also lists 10 participants at risk for other adverse events and 0 affected, and 0 deaths. These are the safety figures recorded for the group; they do not provide event descriptions because no top serious terms are listed.
In general, a count of zero recorded events means that no events of that type were reported in the specified group and record. It does not prove that an event cannot occur, and it does not by itself establish the completeness of follow-up or event ascertainment. The registry record does not report the safety observation period, definitions or collection procedures for adverse events, or detail on how missing safety information was handled.
The group’s listed at-risk count is the denominator recorded for the safety entries, but it should not be confused with a comparative safety estimate. This is a single-group study, with no control arm for a like-for-like comparison. The figures therefore describe the recorded counts in the remifentanil infusion and recovery group; they do not quantify a difference relative to another treatment or population.
12. What the Result Does, and Does Not, Mean
The registry record establishes that investigators studied PUAL during remifentanil infusion and recovery in subjects aged 40–60, with the aim of distinguishing specified opioid concentration categories. It identifies the primary endpoint as an AUROC based on PUAL classification and specifies a 95% confidence interval as the uncertainty measure. These details describe the question and intended summary statistic.
The record does not report a numerical AUROC, confidence interval limits, or another primary outcome estimate. As a result, the posted information does not show how well PUAL distinguished the categories in this study or how precisely that performance was estimated. A missing numerical result is not a finding of no discrimination, and it is not a finding of successful discrimination. It leaves the empirical answer unavailable in the registry record.
The study’s rationale refers to prior investigation in subjects aged 20–40 and to population data about age-related declines in pupil size and PUAL. Those statements provide context for studying the 40–60 age group, but they are not results from the enrolled group. The registry’s stated objective to explore whether PUAL is a sensitive indicator likewise describes the purpose of the investigation, not an observed conclusion.
The design has one group and no like-for-like control comparison. The AUROC, if reported, would address discrimination between concentration categories in the analyzed data; it would not alone establish a causal effect, prove that a measurement strategy improves decisions, or demonstrate performance in populations beyond those studied. The record does not report enough analysis detail to assess the handling of repeated measurements, category membership, missing observations, or the analysis population.
The safety entries record 0 serious adverse events, 0 other adverse events, and 0 deaths among the listed group’s at-risk participants. These counts are descriptive and have no comparison arm. Taken together, the record describes a completed study and its intended endpoint, but the absence of numerical efficacy or discrimination results means that its main statistical question remains unanswered in the posted registry results.
13. Why This Trial Matters Statistically
Statistically, the study is notable for framing its primary question as classification rather than a conventional comparison between treatment groups. PUAL is used to distinguish two concentration categories, and the planned summary is an AUROC. This makes the central issue discrimination: whether the measurement separates the defined states. That is a different estimand from a treatment effect, and it requires interpretation in terms of classifier performance and uncertainty.
The age range gives the study a defined population of interest. The registry’s background explains that earlier investigation concerned subjects aged 20–40 and that pupil size and PUAL decline slightly with age in population data. That context motivates examining subjects aged 40–60, but it does not make results from one age group interchangeable with another. Any claim about performance in the current group would need to be supported by its own reported estimate and uncertainty; those numerical results are not reported in the registry record.
The repeated measurement schedule also makes the data structure important. A baseline measure and repeated observations during infusion and recovery can capture patterns over time, but those observations may be statistically dependent within participants. General statistical practice requires attention to the analysis unit and dependence when estimating uncertainty. The registry record does not state how those features were handled, so readers cannot assess the method’s adequacy from the record.
The endpoint also illustrates why classification estimates need to be read alongside threshold definitions and practical operating characteristics. AUROC provides a summary across thresholds, while a particular use of PUAL would involve a decision threshold and the consequences of errors. The registry identifies concentration categories but does not report the PUAL cutoff or classification details. These distinctions matter even when an AUROC is available; in this record, the numerical AUROC is also absent.
Finally, the record distinguishes study enrollment from planning calculations and observed performance. Enrollment is 10, while the listed planning assumptions are described as an illustration rather than as the original study design. Neither fact supplies a missing endpoint result. The statistical value of this study’s question is clear, but its reported record does not permit a conclusion about discrimination or precision.
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 for statistical interpretation is that the registry record does not report the primary AUROC estimate or its 95% confidence interval limits. Without those values, neither discrimination nor precision can be described. The endpoint is defined, but its result is not available in the posted record.
The record lists enrollment of 10, but it does not report the number of participants or observations contributing to the primary analysis, or how many observations fell into each concentration category. The measurement schedule creates repeated observations, yet the record does not explain whether the analysis treated the participant or the measurement as its unit, or how within-participant dependence was handled. This makes it difficult to assess the effective information underlying any estimate, even if a numerical estimate had been reported.
The concentration categories are stated as <1.8 ng/mL and >2.5 ng/mL. The registry does not describe how values between those limits were handled, how concentration measurements were paired with pupillary measurements, or how the dichotomous PUAL classification threshold was chosen. Without those details, the endpoint’s operational implementation and reproducibility are not fully assessable.
The single-group design has no randomized control comparison, and masking is listed as none. That design fits a classifier-discrimination objective but does not support a randomized treatment contrast. The record does not report adjustment for other factors or a causal analysis. It also does not report an analysis population, missing-data approach, multiplicity plan, confidence-interval method, or detailed statistical analysis plan.
Finally, the registry’s safety entries include no reported events, but the observation period and ascertainment procedures are not described. The available record is therefore limited both in outcome reporting and in methodological detail. These are limitations of what can be evaluated from the registry record, not proof that additional methods or data do not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age — NCT05391555.
- Registry record last updated 2025-05-02; status last verified 2025-04.
- Results first posted 2025-05-02.
- 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.
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18. Record Summary
NCT05391555 is a completed, single-group study sponsored by the University of California, San Francisco, with enrollment of 10 and Phase 2 and Phase 3 labels. The study examined PUAL during remifentanil infusion and recovery in subjects aged 40–60. The registered primary endpoint uses an AUROC to assess discrimination between zero-to-moderate opioid concentration (<1.8 ng/mL) and high-toxic opioid concentration (>2.5 ng/mL).
The registry records a 10-minute infusion, a 25-minute recovery period, and pupillary measurements at baseline and every 2.5 minutes during infusion and recovery. The primary endpoint’s numerical estimate and confidence interval limits are not reported in the registry record. Statistical analysis details, including the analysis population and handling of repeated or missing observations, are also not reported.
For the listed group, the registry records 0 serious adverse events, 0 other adverse events, and 0 deaths. The study’s design and endpoint define the intended statistical question, but the missing outcome estimate prevents assessment of the observed discrimination or its precision.