Prevention of Opioid-Induced Hypoxemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prevention of Opioid-Induced Hypoxemia (NCT04453722), a registered phase not stated study. The primary outcome is Time-weighted Average of SpO2 Below a Threshold of 90%.

2. Clinical Question

The brief study summary describes its purpose as evaluating the feasibility of a fully randomized validation trial for the Oxalert EPO. That objective is distinct from demonstrating the effectiveness of a device mode. The registry record identifies the device conditions and outcomes, but does not report enough primary-outcome information to assess a comparative effect.

3. Trial Design

The registry lists this study as completed, with an enrollment of 49 and a condition of non-cardiac surgery. The listed start date is 2020-06-26 and the primary completion date is 2022-04-30. The sponsor is The Cleveland Clinic. The stated purpose is to evaluate the feasibility of a fully randomized validation trial for the Oxalert EPO.

Two device conditions are described. In monitor-only mode, Oxalert is used in monitor-only mode. In monitor normal mode, Oxalert provides progressive audible and tactile alerts for hypoxemia. Although the brief summary refers to a future fully randomized validation trial, the registry record does not state that allocation in this study was randomized. It explicitly notes that allocation was not stated and that the arms are not a like-for-like control comparison. These details limit the interpretation of any between-arm contrast.

The primary outcome is the time-weighted average of SpO2 below 90%. Its stated timeframe is during hospitalization up to 6 days and post-discharge 24 hours. The record notes that the number of participants analyzed for the in-hospital and post-discharge outcomes differs. Patients' and nurses' attitudes toward the device are listed as secondary outcomes.

The registry lists 7 outcome measures and 39 analyses. Those counts alone do not establish how many analyses concern the primary endpoint, which analysis was prespecified as the principal comparison, or whether any analysis was exploratory. The statistical analysis plan, including adjustment methods and the handling of missing observations, is not reported in the registry record. The design should therefore be read as a completed device study with an explicitly stated feasibility purpose, rather than assumed to be a definitive randomized comparison.

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: number of participants analyzed for in hospital outcome and post-discharge outcome are different

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 Time-weighted Average of SpO2 Below a Threshold of 90%, measured over during hospitalization up to 6 days and post-discharge 24 hours.

The primary endpoint is the time-weighted average of oxygen saturation below a threshold of 90%, reported in % of SpO2. The registry describes oxygen saturation as measured between 0% and 100% and considers oxygen saturation below 90% abnormal. The timeframe covers hospitalization up to 6 days and post-discharge 24 hours.

In general, a time-weighted summary is intended to represent measurements over an observation period while accounting for their duration, rather than treating each isolated reading as the whole clinical course. A summary focused on values below a threshold can describe the extent of low oxygen saturation under the endpoint's definition. The exact weighting procedure, measurement frequency, and rules for gaps in monitoring are not reported in the registry record, so the calculation cannot be reconstructed from the endpoint description alone.

The endpoint is reported using a median and inter-quartile range. In general, the median describes the middle of a distribution, while the inter-quartile range describes the spread of its central portion. These summaries can be informative when outcomes are skewed or include unusually high values. They do not, by themselves, give the mean difference between arms or establish how precisely an estimated contrast is known.

Separate analyzed populations are noted for the in-hospital and post-discharge outcomes. The numerical endpoint results, group-level medians and inter-quartile ranges, and any estimated between-arm contrast are not reported in the registry record. As a result, the endpoint's definition can be described, but its observed distribution and comparative result cannot.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a time-weighted average of SpO2 below a threshold of 90%, and identifies the summary parameter as the median with an inter-quartile range. It does not report the numerical primary-outcome results or the statistical analysis plan. The explanations below describe general statistical ideas, not methods confirmed as having been used in this study.

What does a time-weighted outcome represent?

In general, a time-weighted measure combines observations over time so that the duration associated with measurements contributes to the summary. This can be useful when the clinical question concerns exposure over a monitoring period rather than a single reading. Here, the endpoint description focuses on oxygen saturation below the stated threshold and gives separate in-hospital and post-discharge timeframes. The registry does not explain the exact weighting formula, how measurements were collected, or how missing intervals were treated. Those details are needed to reproduce the endpoint and to understand how monitoring coverage influences it.

Why report a median and inter-quartile range?

In general, the median is a measure of the center of a distribution that is less affected by extreme values than the arithmetic mean. The inter-quartile range describes the spread of the central part of the observed values. These statistics are often useful when data are skewed or when a small number of observations are far from the rest. They describe the distribution within a group; they are not, on their own, an estimate of the difference between groups. An inferential comparison would require a stated method and a reported estimate with its uncertainty.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical model and procedure. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. An interval should be considered alongside the estimate and the study design. It cannot correct for systematic differences between groups caused by non-random allocation, and it does not show that a result is clinically important by itself. A confidence interval for the primary endpoint contrast is not reported in the registry record.

Why does the allocation caveat matter?

Random allocation, when used and properly implemented, aims to balance measured and unmeasured characteristics between groups on average. The registry record does not state the allocation method and specifically cautions that the arms are not a like-for-like control comparison. As a general principle, this makes an unadjusted group contrast vulnerable to confounding: differences in participants or care may contribute to any observed outcome difference. Adjustment can sometimes address measured differences, but cannot guarantee removal of unmeasured confounding. The adjustment plan and participant characteristics needed to assess this are not reported in the registry record.

How should planning calculations be read?

The registry describes sample-size calculations as planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also says that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the original study was designed with those assumptions. A calculation based on an observed effect is sensitive to how that effect was estimated and should not be described as observed power. Planning numbers indicate hypothetical requirements under stated assumptions; they do not show what the study actually had power to detect.

The registry notes that time-to-event planning tables express the total number of events, while other planning tables express participants per arm. This distinction is general: for time-to-event designs, information often depends substantially on the number of observed events, whereas other designs commonly express a target sample size by group. The numerical planning outputs and the stated fractions are not included in the record information available for this interpretation, so no such values can be described.

What can be inferred from multiple analyses?

The record lists 7 outcome measures and 39 analyses. In general, examining multiple outcomes, timeframes, or analysis choices can increase the chance that at least one result appears notable by chance if no adjustment or prespecified hierarchy is used. Multiplicity methods can control or describe this issue, but their appropriateness depends on the questions and analysis plan. The registry does not report whether tests were adjusted, whether a primary analysis was designated among the listed analyses, or whether analyses were prespecified. The count of analyses alone does not establish that multiplicity correction was required or omitted.

The statistical methods used for the primary endpoint, including any model, covariate adjustment, hypothesis test, missing-data procedure, and confidence-interval construction, are not reported in the registry record. Consequently, the posted endpoint definition and summary type can be explained, but the primary comparison cannot be independently assessed for model choice, assumptions, or precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and 39 analyses, but it does not explain the relationship between these analyses, identify a prespecified testing hierarchy, or report whether multiplicity was addressed. In general, testing several outcomes or analysis variations can make isolated findings harder to interpret because the chance of at least one apparently unusual result may increase. A statistical plan can address this through a prespecified primary analysis, adjustment procedures, or a clear distinction between confirmatory and exploratory analyses. The registry record does not report which approach, if any, was used.

Missing-data handling is also not reported in the registry record. The primary outcome description states that the numbers analyzed for the in-hospital and post-discharge outcomes differ. The reasons for this difference, the amount and pattern of missing outcome data, and any assumptions or methods used to address missingness are not reported. In general, missingness can affect estimates when the availability of observations is related to participant characteristics or outcomes. The differing analyzed populations mean the two timeframes should be interpreted separately rather than presumed to describe the same analysis population.

The registry does not report the analysis population definition, exclusions, or whether analyses followed an intention-to-treat or another approach. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. These gaps limit assessment of both selection effects and the comparability of the groups. Without a statistical analysis plan and participant flow details, it is not possible to determine whether the posted analyses followed prespecified methods or how missing observations affected them.

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.

Most frequent non-serious adverse event terms

The registry lists zero serious adverse events among 24 participants at risk in Oxalert in Monitor Only Mode and zero serious adverse events among 25 participants at risk in Oxalert in Monitor in Normal Mode. It lists other adverse events among 24 and 25 participants at risk, respectively: 3 in the monitor-only arm and 2 in the monitor-normal arm. Deaths are listed as 0 in each arm.

These figures are descriptive counts. They do not establish that the modes have equivalent safety, nor do zero serious events show that such events are impossible. Interpretation depends on event definitions, the observation period, ascertainment, and completeness of follow-up. The registry record does not report detailed definitions or descriptions for the other adverse events, or the method used to collect events.

The at-risk counts listed for adverse events should not be assumed to be the numbers analyzed for the primary outcome. The registry explicitly says that the analyzed populations for the in-hospital and post-discharge primary outcomes differ. Safety counts also do not indicate whether an event was caused by a device or by other aspects of care. The record does not report a causal assessment, so these counts should be read as recorded events by arm rather than as treatment-attributed effects.

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

The record establishes that a completed study examined Oxalert device modes in the setting of non-cardiac surgery, with a stated purpose of evaluating the feasibility of a fully randomized validation trial. It identifies a primary oxygen-saturation endpoint and describes secondary outcomes concerning patients' and nurses' attitudes toward the device. It also lists adverse-event counts for the two arms.

What the record does not establish is the comparative primary-outcome result. Numerical group summaries, an estimated contrast, and uncertainty for the endpoint are not reported in the registry record. Without those values, it is not possible to describe the size, direction, or precision of a difference in time-weighted SpO2 below 90%. The endpoint's definition alone is not evidence that either device mode changed oxygen saturation.

The record also does not establish a randomized causal comparison. It says allocation was not stated and that the arms are not a like-for-like control comparison. Consequently, even a reported difference would require cautious interpretation because group composition or other factors could explain some or all of it. A feasibility objective should not be confused with evidence of clinical benefit or lack of benefit.

The adverse-event counts are useful as a registry description, but they do not establish equivalent safety or attribute events to a device. The record's incomplete information on event definitions, missing observations, and analysis populations further limits interpretation. The most defensible reading is therefore a description of the study's purpose and registered outcomes, with explicit acknowledgment that the primary comparative result and key analysis details are unavailable in the registry record.

13. Why This Trial Matters Statistically

This study raises statistical questions that are important in device research. Its stated aim is feasibility for a fully randomized validation trial, while the registry cautions that the recorded arms are not a like-for-like control comparison and does not state allocation. Distinguishing feasibility from a causal treatment comparison is essential: a study can be informative about whether a larger trial can be pursued without providing a reliable estimate of comparative effect.

The endpoint also illustrates why outcome definitions matter. A time-weighted average below a threshold is intended to describe oxygen-saturation experience across a monitoring period, rather than relying on an isolated reading. Its interpretation depends on the monitoring schedule, the handling of gaps, and the precise weighting method. Those implementation details are not reported in the registry record, so readers cannot fully assess how the measure was constructed.

Separate analysis populations for the in-hospital and post-discharge outcomes highlight the importance of participant flow and missing-data reporting. If different participants contribute to different timeframes, apparent differences across periods may reflect both time and population composition. The registry record does not provide the details needed to disentangle these possibilities.

Finally, the record lists many analyses relative to its outcome measures, yet does not describe a testing hierarchy or multiplicity strategy. This is a reminder that a count of analyses is not enough to judge the credibility of individual findings; prespecification, transparency, and uncertainty estimates matter. In this case, primary numerical results are not reported in the registry record, making restraint in interpretation especially important.

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.

A central limitation is that the primary outcome is described but its numerical results are not reported in the registry record. No group medians, inter-quartile ranges, comparative estimate, or confidence interval are available in the record information. Thus, the endpoint can be explained, but its observed distribution, direction of contrast, and precision cannot be evaluated.

The registry says allocation was not stated and cautions that the arms are not a like-for-like control comparison. This limits causal interpretation and makes it inappropriate to treat an observed between-arm difference as necessarily caused by device mode. The record does not give baseline characteristics or details that would allow an assessment of group comparability.

The analyzed populations differ between the in-hospital and post-discharge outcomes. The reasons, participant flow, missing-data pattern, and statistical handling of missing observations are not reported in the registry record. The endpoint description also does not specify the weighting formula, measurement schedule, or handling of monitoring gaps.

Although the registry lists 7 outcome measures and 39 analyses, it does not report a prespecified analysis hierarchy, multiplicity approach, or which analyses were confirmatory. The analysis plan, endpoint estimation methods, and inferential procedures are not reported. For safety, the record lists event counts but does not report detailed definitions for other adverse events or attribution to the device. These limitations constrain interpretation without implying that unreported procedures or results were absent from the conduct of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prevention of Opioid-Induced Hypoxemia — NCT04453722.
• Registry record last updated 2025-08-29; status last verified 2025-08.
• Results first posted 2024-02-20.
• 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

The registry record describes a completed study titled “Prevention of Opioid-Induced Hypoxemia,” sponsored by The Cleveland Clinic, in non-cardiac surgery. It lists an enrollment of 49, a start date of 2020-06-26, and a primary completion date of 2022-04-30. The stated objective is to evaluate the feasibility of a fully randomized validation trial for the Oxalert EPO.

The two listed device conditions are monitor-only mode and monitor normal mode, the latter described as providing progressive audible and tactile alerts for hypoxemia. The primary endpoint is the time-weighted average of SpO2 below 90%, summarized by median and inter-quartile range during hospitalization up to 6 days and post-discharge 24 hours. The record notes that the analyzed populations differ by timeframe. Patients' and nurses' attitudes toward the device are listed as secondary outcomes.

Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. Numerical primary-outcome results and key analysis details are not reported in the registry record.