Evaluation of Modafinil vs Placebo for Treatment of Anesthesia Delayed Emergence in Obstructive Sleep Apnea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Modafinil vs Placebo for Treatment of Anesthesia Delayed Emergence in Obstructive Sleep Apnea (NCT02494102), a randomized phase 4 study. The primary outcome is Length of Time From Extubation to Discharge From Postanesthesia Recovery Unit.

2. Clinical Question

In statistical terms, the trial was designed to compare outcomes between two assigned groups, rather than to compare each participant with an untreated version of themselves. Random allocation can support a causal comparison when the analysis follows an appropriate plan and preserves the randomized groups. However, the record does not report the analysis population or the handling of the 16 protocol violations in enough detail to establish how the primary outcome was analyzed.

The registry lists Postanesthesia Quality Recovery Scale Score as a secondary outcome, measured at baseline and 6 hours after surgery. Its posted summaries include an unadjusted between-group comparison. That secondary result is distinct from the primary recovery-time question and cannot substitute for a reported primary endpoint analysis.

3. Trial Design

This was a Phase 4, randomized, double-blind, parallel-group study sponsored by Milton S. Hershey Medical Center. The registry lists an enrollment of 105. The study began in 2016-02, had a primary completion date of 2018-04-01, and is recorded as terminated. The reason for termination is not reported in the registry record.

Participants were assigned to modafinil or placebo. The intervention description specifies 200mg of modafinil before general anesthesia and surgery on the day of surgery. The placebo description also places administration immediately before anesthesia and surgery. The record identifies the study as double blind but does not report further detail about who was masked, how masking was maintained, or whether masking was assessed.

The primary endpoint was the length of time from extubation to discharge from the postanesthesia recovery unit, expressed in minutes, with a 24-hour timeframe. The registry describes the outcome parameter as a mean and its dispersion as an inter-quartile range. The posted group summaries report 53.5 minutes for placebo, with an inter-quartile range from 41.0 to 80.0, and 61.0 minutes for modafinil, with an inter-quartile range from 46.0 to 91.0. The corresponding groups include 42 and 47 participants, respectively. No between-group analysis of this primary endpoint is reported.

The secondary outcome was Postanesthesia Quality Recovery Scale Score at baseline and 6 hours after surgery. The registry posts summaries for 42 placebo participants and 47 modafinil participants. The reported outcome population and the relation between these counts, the enrollment of 105, and the protocol violations are not fully described in the registry record. The planned sample-size justification, allocation procedure details, and full statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 16 patients violated the study protocol and were excluded from the study. Exclusions included Day of Surgery refusal of study medication, surgical case cancellation, and surgeon refusal to participate.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 16 participants violated the study protocol

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: 16 patients violated the study protocol and were excluded from the study.

6. Primary Endpoint

The registry lists the primary outcome as Length of Time From Extubation to Discharge From Postanesthesia Recovery Unit, measured over 24 hours.

The primary endpoint measures the elapsed time between extubation, when the breathing tube is removed, and discharge from the postanesthesia recovery unit. It is recorded in minutes and was specified for a 24-hour timeframe. This outcome is a measure of recovery-unit duration after general anesthesia, rather than a direct measurement of the cause of delayed emergence.

Time to discharge can be useful as a clinical-trial endpoint because it records when a participant reaches a defined transition in postoperative care. Comparing groups on this measure asks whether their recovery-unit times differ under the study conditions. The result can be affected by more than emergence from anesthesia: discharge processes, local criteria, staffing, and other postoperative circumstances may also influence when discharge occurs. These are general considerations; the registry record does not report which criteria or procedures were used to determine discharge.

The record describes the primary outcome using a mean and inter-quartile range. The posted summaries are 53.5 minutes for placebo and 61.0 minutes for modafinil, with inter-quartile ranges of 41.0 to 80.0 and 46.0 to 91.0, respectively. Those summaries describe the groups, but they do not by themselves establish whether the observed difference is compatible with chance variation or estimate its precision. A primary between-group analysis, including an uncertainty interval or test result, is not reported in the registry record. Consequently, the primary endpoint's inferential result cannot be characterized from the posted summaries alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study used a randomized, double-blind, parallel-group design. Randomization is intended to make the assigned groups comparable, on average, with respect to factors that could affect outcomes. In a parallel design, participants remain in their assigned group for the trial comparison. Double blinding is intended to reduce the influence of treatment knowledge on participant experience, care, and outcome assessment. These are general purposes of the design features; the registry record does not describe the randomization sequence, concealment procedures, or the individuals who were masked.

What a group summary can tell us

A group mean describes the average value in that group. An inter-quartile range describes the middle half of the observed values, from the 25th percentile to the 75th percentile. These summaries answer descriptive questions: what values were observed, and how were they distributed within each group? They do not quantify the uncertainty in the difference between groups. A confidence interval for a between-group effect is needed to show a range of effect sizes compatible with the data under the analysis assumptions. The primary outcome's posted group summaries do not include a reported confidence interval or test result.

For the primary endpoint, the registry describes the parameter as a mean and the dispersion as an inter-quartile range. Means can be sensitive to unusually high or low observations, while the inter-quartile range is less influenced by extremes. Reporting both can give complementary descriptive information. However, the record does not report the underlying observations, the distribution of recovery times, or the statistical model used for a primary comparison. The record also does not report an analysis of the primary outcome, so no inferential method for that endpoint can be evaluated.

How to read a confidence interval

In general, a confidence interval describes uncertainty in an estimated effect under a specified statistical procedure. A narrower interval indicates greater precision than a wider interval, conditional on the method and data. It is not a guarantee that the true effect lies within the particular interval. For the secondary scale comparison, the posted unadjusted mean difference is -3.24, with a 95% confidence interval from -5.934 to -0.546. This interval describes uncertainty around that unadjusted estimate under the calculation used; it does not account for any multiplicity adjustment, and no such adjustment is reported in the registry record.

The accompanying unadjusted p-value is 0.018. A p-value measures how unusual data at least as incompatible with a null comparison would be under the assumptions of the test if the null were true. It does not express the probability that the null hypothesis is true, the probability that the result occurred by chance, or the size or clinical importance of an effect. The result is unadjusted, and the registry record does not report whether the secondary outcome was selected for emphasis in advance or whether other analyses were conducted but not posted.

Why distribution and model choices matter

General statistical principle: some outcome distributions are more variable than a simple model assumes. Over-dispersion means observed variability exceeds the model's expected variability. If unaccounted for, standard errors can be too small and uncertainty intervals too narrow. Recovery time may be skewed in some settings, but the registry record does not report a distributional assessment or a model for the primary endpoint. No claim about over-dispersion in this trial can therefore be made.

For continuous outcomes, a comparison of means typically estimates a difference in average values. The secondary outcome's posted comparison uses a mean difference. A standard deviation summarizes the spread of individual values around a mean, whereas a standard error summarizes uncertainty in an estimated quantity. These are not interchangeable. The secondary group standard deviations are reported as 4.74 for placebo and 7.98 for modafinil. The secondary comparison also reports an unadjusted effect estimate and confidence interval. No covariate-adjusted model is reported, so the comparison should be interpreted as unadjusted rather than as an adjusted estimate.

What the planning illustration means

The planning illustration is based on the observed secondary effect and is not the trial's own design justification. Its assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. For planning to detect 100% of the observed effect, it lists 67 participants per arm for 80% power and 89 participants per arm for 90% power. Planning to detect 75% of the observed effect lists 118 participants per arm for 80% power and 158 for 90% power. Planning to detect 50% of the observed effect lists 265 participants per arm for 80% power and 355 for 90% power.

These values are prospective planning illustrations conditional on the stated assumptions. They are not observed power, do not describe the probability that the trial's findings are correct, and do not show what the investigators used to choose enrollment. The study's own sample-size assumptions and justification are not reported in the registry record. Planning illustrations based on an observed effect can also be optimistic when that effect is estimated with uncertainty; smaller assumed effects require larger planned groups under the stated framework.

Analysis population and missing information

The primary-outcome description refers to 16 protocol violations, but it does not define the analysis population or explain whether those participants were excluded, retained, or analyzed separately. The posted primary and secondary group summaries include 42 participants in placebo and 47 in modafinil. The registry record does not explain how those numbers relate to the enrollment of 105 or provide a participant flow accounting for missing outcomes, withdrawals, or exclusions. Without that information, it is not possible to assess whether missingness or deviations could have affected the reported comparisons.

The registry lists no reported analyses for the secondary outcome, although it posts group summaries and an unadjusted comparison. This distinction matters: a numerical comparison can be calculated from posted summary statistics, but the registry does not thereby document the full prespecified analysis, its assumptions, or its place in the planned testing strategy. Details of covariate adjustment, multiplicity control, interim analyses, and sensitivity analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical plan for controlling the risk of false-positive findings across multiple outcomes or analyses. It does not describe a testing hierarchy, a designated order for interpreting outcomes, or an adjustment to the secondary comparison. The posted p-value for the scale outcome is unadjusted. An unadjusted result addresses that comparison on its own and does not account for the possibility that other outcomes or analyses were also examined.

The registry lists one secondary outcome but also records no reported analyses for it. This does not establish how many analyses were performed, which were planned, or whether unposted analyses exist. The analysis plan, any interim analyses, and any decision rules for stopping or changing the study are not reported in the registry record. The study status is terminated, but the reason for termination is not reported and should not be inferred from that status alone.

Missing-data handling is also unclear. The registry does not provide a participant flow or explain whether outcomes were unavailable for any enrolled participants. It notes 16 protocol violations in the primary-outcome population description, but does not specify the nature of the violations, the participants involved, or their treatment in the analysis. The reported group sizes for the primary and secondary summaries are 42 and 47. The relationship of these counts to the enrollment of 105 is not fully described.

Analysis populations can differ: an intention-to-treat analysis generally retains participants in their randomized groups, while a per-protocol analysis may exclude participants who did not follow key procedures. Those are general concepts. The registry record does not identify the primary analysis population as either approach, nor does it report sensitivity analyses comparing alternative populations or missing-data assumptions. These omissions limit assessment of bias from exclusions, missing outcomes, or deviations from the assigned intervention.

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 reports zero serious adverse events among 42 participants in the placebo group and zero among 47 participants in the intervention group. It also reports zero other adverse events and zero deaths in each group. These counts describe the posted safety results for the groups and participants represented in those summaries.

A zero count does not establish that an event is impossible or that there is no risk. Safety interpretation depends on the period of observation, the definitions used, how events were collected, and how completely participants were followed. The registry record does not provide further detail about event definitions, follow-up completeness, or the approach to collecting adverse events. The study is recorded as terminated, but its reason for termination is not reported; the status alone does not explain the safety findings.

With no serious events posted in either group, the registry record does not support a comparative estimate of serious-event risk. These counts also should not be interpreted as a complete characterization of safety beyond the recorded participants and reporting period. They are descriptive figures, not evidence that either intervention is risk-free.

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

The registry record describes a randomized, double-blind comparison of modafinil and placebo before general anesthesia in patients with obstructive sleep apnea. It posts primary recovery-time summaries and a secondary recovery-scale comparison. The primary outcome summaries describe the observed groups, but the record does not report a statistical comparison of those groups. As a result, the principal trial question cannot be answered inferentially from the primary endpoint results posted in the record.

The secondary outcome has an unadjusted mean difference of -3.24 and an unadjusted p-value of 0.018. That finding concerns a scale-based secondary measure at baseline and 6 hours after surgery. It is not a test of the primary recovery-time endpoint. Without information about the scale's clinically meaningful threshold, the multiplicity strategy, and the prespecified analysis plan, the size and confirmatory importance of this secondary finding remain uncertain.

These data do not establish whether modafinil changes the time from extubation to discharge from the postanesthesia recovery unit. They also do not establish that the secondary scale result is clinically important, that it represents a causal effect free of analysis limitations, or that the intervention is effective or ineffective. A p-value does not measure clinical importance, and a group summary alone does not demonstrate that an observed difference is reliable.

The trial's randomized and double-blind features are relevant strengths of its design. Interpretation is nonetheless limited by the absence of a reported primary comparison, incomplete information about the analysis population and protocol violations, and missing detail about multiplicity and missing-data handling. The reason the study was terminated is not reported in the registry record. A full interpretation would require the prespecified statistical plan, participant flow, outcome analysis details, and sufficient context for the recovery scale and discharge procedures.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between collecting an outcome and reporting an analysis of that outcome. The registry identifies a primary endpoint and provides group summaries, but does not report the between-group estimate or its uncertainty. A descriptive difference may be visible in group summaries, yet statistical interpretation requires an analysis that addresses variability and provides an appropriate measure of uncertainty.

It also shows why outcome hierarchy matters. The secondary scale outcome has a posted unadjusted comparison, but the primary endpoint does not have a reported comparison. A secondary result cannot automatically replace the primary analysis, particularly when the registry does not describe how multiple outcomes were handled or whether the secondary analysis was intended to be confirmatory.

The population description raises another practical issue: the record notes 16 protocol violations, while the analysis population and the handling of those participants are not explained. Randomization protects comparisons most directly when analysis choices preserve the intended comparison and are transparent. Without details about exclusions, missing outcomes, and analysis populations, readers cannot fully judge how robust the findings are to those choices.

Finally, the planning illustration makes clear that sample-size calculations depend on an assumed effect and stated statistical assumptions. Those figures are not a reconstruction of the investigators' original design rationale and are not observed power. The study's own sample-size justification is not reported in the registry record. Taken together, these features make the record useful for understanding what was planned and what summaries were posted, while demonstrating why complete endpoint analyses and transparent methods are necessary for firm statistical interpretation.

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.

Several limitations are specific to the information available for this trial. The primary endpoint is named and summarized by group, but no primary between-group estimate, confidence interval, or p-value is reported. The posted means and inter-quartile ranges cannot replace an inferential analysis or show how precise a treatment contrast might be.

The primary-outcome description says 16 participants violated the study protocol, but does not say what the violations were or how they affected eligibility for the analysis. The registry does not identify whether the primary analysis was intention-to-treat, per-protocol, or another approach. It also does not provide a participant flow explaining the relation between the enrollment of 105 and the 42 placebo and 47 modafinil participants in the posted outcome summaries.

The reason for the terminated study status is not reported in the registry record. It is therefore not possible to determine whether termination related to recruitment, feasibility, safety, efficacy, or another consideration. Interim analyses and stopping criteria are also not reported. No explanation is available for missing or unposted outcome data.

The secondary comparison is unadjusted, and its status within a prespecified analysis plan is unclear. The record does not report multiplicity control, an outcome hierarchy, the clinical interpretation of the scale, or a threshold for meaningful change. It also does not report the primary endpoint's analysis model or distributional assessment. These gaps prevent a complete assessment of precision, robustness, and the relationship between the primary and secondary findings.

Finally, the safety figures are counts without detailed definitions or follow-up information. They describe the recorded groups, but cannot establish the completeness of event ascertainment or characterize risks beyond the reported observation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Modafinil vs Placebo for Treatment of Anesthesia Delayed Emergence in Obstructive Sleep Apnea — NCT02494102.
• Registry record last updated 2019-06-20; status last verified 2019-06.
• Results first posted 2019-06-20.
• 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

NCT02494102 is a Phase 4 randomized, double-blind, parallel-group study sponsored by Milton S. Hershey Medical Center. It evaluated modafinil versus placebo before general anesthesia in patients with obstructive sleep apnea and is recorded as terminated. Enrollment was 105; the study began in 2016-02 and its primary completion date was 2018-04-01. The reason for termination is not reported in the registry record.

The primary endpoint was time from extubation to discharge from the postanesthesia recovery unit, measured in minutes over a 24-hour timeframe. Group summaries are posted for 42 placebo participants and 47 modafinil participants, but no primary between-group analysis is reported. A secondary recovery-scale outcome at baseline and 6 hours after surgery has an unadjusted comparison. The registry does not report the analysis plan, the handling of the noted protocol violations, or the reason for termination.