Investigation of Pupillometry as Guide for Extubation Readiness in Anesthetized Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of Pupillometry as Guide for Extubation Readiness in Anesthetized Children (NCT04947397), a randomized na study. The primary outcome is Extubation Success.

2. Clinical Question

The trial compares two approaches to the timing or guidance of deep extubation. Its primary endpoint is a participant count: extubation success is defined by maintaining spontaneous ventilation without a pathologic airway response, with laryngospasm given as an example. The registry record also describes how ventilation was monitored, including chest wall movement, capnography, reservoir bag movement, mask condensation, and auscultation.

The posted primary result is the same in both groups: all 10 participants in each group met the success definition. This is a description of the observed trial results, not a conclusion that the approaches are equivalent in a broader population. The small number of participants and the limited precision of the record’s reported comparisons matter when interpreting what can be learned. The secondary outcome records anesthetic vapor concentration at extubation, which adds information about the anesthetic conditions accompanying the two approaches but is not itself the primary success endpoint.

3. Trial Design

The registry lists this study as a randomized, parallel-group trial with no masking. It reports an enrollment of 20 and a completed status. The record identifies the sponsor as the University of California, San Francisco, and gives a start date of 2022-06-20 and a primary completion date of 2023-02-01. The phase is listed as NA.

The two groups are described as Group 1, traditional deep extubation at 1.5 MAC, and Group 2, deep extubation guided by pupillometry at < 0.5 MAC of vapor plus propofol and fentanyl. The intervention is listed as a diagnostic test called Pupillometry. The displayed primary outcome data include 10 participants in each group. The registry does not report further operational details about how participants were randomized, whether allocation was concealed, or how the pupillometry guidance was applied beyond the brief arm description.

The primary outcome is extubation success immediately after extubation. The registry defines success as maintenance of spontaneous ventilation without a pathologic airway response such as laryngospasm. Anesthetic vapor concentration at extubation is the secondary outcome with posted results. Although the record lists three outcome measures, results are posted for one secondary outcome. It reports three outcome measures overall and zero analyses in the record-level analysis count; the registry does not describe a statistical analysis plan or analysis population.

Because the study is unmasked, the registry does not describe blinded treatment assignment or outcome assessment. That does not by itself establish whether assessment was influenced by knowledge of group assignment; the record does not provide enough information to determine that. Details such as eligibility criteria, participant flow, protocol deviations, and the rationale for the planned enrollment 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.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Extubation Success, measured over Immediately after extubation.

The primary endpoint is a count of participants who achieved extubation success immediately after extubation. The registry’s definition requires maintenance of spontaneous ventilation and no pathologic airway response, with laryngospasm named as an example. Ventilation was monitored using chest wall movement, capnography, reservoir bag movement, condensation of the anesthetic mask, and auscultation.

This endpoint focuses on an immediate event around extubation rather than a later outcome. In general, a binary endpoint such as success or failure can summarize whether each participant met a prespecified criterion, and a count can be compared across trial groups. The endpoint is relevant to the stated question because it assesses the respiratory and airway response that the trial is concerned with at the time of extubation. That rationale describes the role of the measure; it does not establish that either strategy is preferable.

The posted counts show that all 10 participants in Group 1 and all 10 participants in Group 2 met the recorded success definition. The registry does not report a separate breakdown of which components of the definition were assessed in each participant, or how any borderline observations were handled. The record also does not provide details about endpoint adjudication. Readers should therefore interpret the result as the posted participant count under the registry’s stated definition, rather than as a more detailed account of every airway or ventilation observation.

7. Results Posted in the Registry

• Group 2: 100.0% (10/10) versus 100.0% (10/10) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Anesthetic Vapor Concentration at Extubation

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Group 2: mean 0.80 versus 3.80 on control; difference -3.00 (95% CI -3.06 to -2.94), standardized effect d = -42.43; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Group 2 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcome is anesthetic vapor concentration at extubation. It provides context about the anesthetic conditions recorded alongside the two extubation approaches, whereas the primary endpoint captures immediate success as defined by spontaneous ventilation without a pathologic airway response. These outcomes address different aspects of the trial: one describes a concentration at a specific time, and the other records whether each participant met the primary success criterion.

The secondary result does not alter the primary finding that the success counts were the same in the displayed groups. Nor does a difference in concentration establish that the difference caused, predicted, or explained the primary outcome. The registry record does not report an analysis relating individual participants’ vapor concentration to their extubation outcome. It also does not describe a mediation analysis or another method for separating the effects of the intervention components.

The registry lists three outcome measures, while the results include one secondary outcome. The record does not explain the status or results of the other outcome measures. This incomplete outcome picture makes it harder to know how the posted secondary result fits within the full set of planned comparisons.

The secondary comparison is labeled unadjusted. In general, when multiple outcomes or comparisons are examined, an unadjusted p-value does not account for the increased opportunity to see a small p-value by chance across that set. Without a reported analysis hierarchy or multiplicity plan, the secondary result carries less confirmatory weight than a single prespecified primary analysis would. This caution is about how much evidential weight to place on the result, not a claim that the measurement is unimportant or that the result is incorrect.

Overall, the secondary measure gives a descriptive account of anesthetic concentration, while the primary measure records immediate extubation success. The registry does not provide enough information to establish a statistical or causal connection between them. They should be read as separate results with different roles in the trial.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Anesthetic Vapor Concentration at Extubation

9. Statistical Interpretation

10. Statistical Methods Explained

The registry lists a randomized, parallel design. In a parallel-group trial, participants are assigned to one of the groups and outcomes are compared across those groups. General statistical context: random assignment is intended to make group comparisons less vulnerable to systematic differences at baseline, but the registry record does not report the sequence-generation or allocation-concealment methods. It is therefore not possible to assess those details from the record.

The primary outcome is binary: each participant either met the extubation-success definition or did not. The posted arm summaries use counts, and the comparison is expressed as a risk difference. General statistical context: a risk difference subtracts one group’s event probability from the other group’s probability. A value of 0.0 indicates no observed difference on that scale. Here, the displayed group results are 10 of 10 in each arm, and the reported risk difference is 0.0. The registry does not report a primary-outcome p-value or the method used to construct the primary confidence interval.

A confidence interval is generally used to show a range of values compatible with data under a particular statistical method. It depends on the method and assumptions used, and it is not a guarantee that the true effect lies in the reported range. The primary interval runs from 0.0 to 0.0, but its construction method is not reported in the registry record. With no observed failures and only 10 participants per group, the displayed interval should not be interpreted as definitive evidence of no possible difference in the wider population.

The secondary outcome is a continuous measure, anesthetic vapor concentration at extubation, summarized as a mean and standard deviation. The posted means are 3.8 for Group 1 and 0.8 for Group 2, with standard deviations of 0.0 and 0.1, respectively. The reported mean difference is -3.0, with a confidence interval from -3.062 to -2.938. General statistical context: a mean difference expresses the contrast between group averages on the outcome’s original scale. The sign indicates the direction of the contrast as represented in the posted comparison; the negative value corresponds to the lower mean in Group 2.

The secondary result also has an unadjusted p < 0.001. General statistical context: a p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. Since the registry does not report the test used or a broader analysis plan, the posted p-value should be read as an unadjusted result rather than as a fully documented confirmatory analysis.

Over-dispersion is a concern in some count outcomes when observed variation exceeds what a simple model expects. General statistical context: this issue is not central to the posted primary endpoint, which is presented as participant counts with a binary outcome, nor is a count-rate model described in the registry record. The secondary endpoint is reported as a mean with a standard deviation, not as an over-dispersed count. No model details are available to assess whether other distributional assumptions were examined.

The registry includes a sample-size planning illustration based on the observed secondary effect, with equal allocation, a two-sided significance level of 0.05, and a normal approximation. It presents planning for 100%, 75%, and 50% of the observed effect. General statistical context: such calculations ask how many participants might be needed under stated assumptions to detect an effect of a chosen size with a chosen power. They are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The registry does not report the trial’s own sample-size justification, so the illustration cannot be used to infer the original enrollment rationale.

The very small standard deviations in the posted secondary data, including a standard deviation of 0.0 in Group 1, can strongly affect a calculation that uses the observed effect and variability. General statistical context: a planning result derived from an unusually large standardized observed contrast can be unstable and may suggest unrealistically small sample sizes. The illustration should therefore be viewed as a mathematical scenario under its stated assumptions, not as a recommendation for a future study. A design should use an independently justified effect size and suitable variability assumptions; those choices are not reported.

The record does not report whether analyses were intention-to-treat, per-protocol, or based on another population. It does not describe missing-data handling, protocol deviations, covariate adjustment, interim analyses, or multiplicity procedures. The absence of these details is an information limitation, not evidence that any particular procedure was or was not used outside what the registry states.

11. Confidence Intervals and Precision

The primary comparison has a risk difference of 0.0 and a reported confidence interval from 0.0 to 0.0. This agrees with the displayed counts: 10 of 10 participants met the success definition in each group. The interval is unusually narrow in appearance, but the registry does not report the method used to calculate it. The interval should not be taken to mean the underlying success probabilities are known without uncertainty.

In general, a confidence interval describes uncertainty around an estimate according to a specified method and its assumptions. Its width is influenced by the information in the data, including the number of participants and the distribution of outcomes. When every participant has the same binary outcome, the observed data provide little direct information about how often failures might occur in a wider population. The reported interval’s form and the limited number of participants make it particularly important not to interpret its endpoints as a definitive boundary on possible population differences.

For the secondary continuous outcome, the reported mean difference is -3.0, with a confidence interval from -3.062 to -2.938. This interval is narrow around the observed contrast. However, precision in a summary comparison is not the same as generalizability, and it does not resolve questions about the analysis method or multiplicity. The registry record reports standard deviations of 0.0 and 0.1 in the two groups, and such low within-group variation can contribute to a narrow interval. The method behind the interval is not described.

Both intervals are results for this trial, not guarantees about future observations. General statistical context: precision should be considered alongside study size, outcome variability, design, and analysis assumptions. Here, the primary result is based on 10 participants per group, and the secondary result’s variability is very low in the posted summaries. The record does not provide enough method detail to independently assess interval construction. Readers should use the intervals as reported while recognizing these limits.

12. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a hierarchy for primary and secondary outcomes, or a procedure for adjusting for multiple comparisons. It lists three outcome measures, but posts results for one secondary outcome. The record does not explain the status of the other outcome measures or whether they were analyzed. These omissions limit assessment of how the displayed results relate to all outcomes considered by the investigators.

The secondary comparison is reported with an unadjusted p-value. General statistical context: when several outcomes are examined, evaluating each at the same nominal threshold without adjustment can increase the chance of at least one apparently notable result, even when none of the underlying effects is real. A prespecified hierarchy or a multiplicity adjustment can help clarify how evidence is evaluated across outcomes. Neither is reported, so the secondary result should not be treated as if the registry documented such a procedure.

The record also does not state how missing data were handled, whether all randomized participants were included in the outcome analysis, or whether participants were excluded after randomization. The displayed group summaries contain 10 participants in each group, matching the reported enrollment of 20, but that alone does not establish the analysis population or confirm that no other data-handling decisions occurred. No participant flow or outcome-specific missingness details are reported.

Other analysis-population details are also absent. The registry does not say whether the primary analysis was intention-to-treat, per-protocol, or based on another definition. It does not describe protocol deviations, interim analyses, covariate adjustment, or sensitivity analyses. These items are not reported in the registry record; their absence should not be interpreted as evidence that a particular method was used or omitted beyond what is posted.

Without those details, the safest reading is to treat the tables as summaries of the posted results and avoid assuming an undocumented analysis strategy. The primary and secondary results can still be described as shown, but the strength and confirmatory status of the secondary evidence are difficult to assess from the registry record alone.

13. 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, zero other adverse events, and zero deaths in Group 1 and in Group 2. Each group has 10 participants listed as at risk for the serious and other adverse-event summaries. These figures describe events recorded in the trial; they do not show that such events are impossible or establish the safety of either approach.

In general, a zero count in a small study means no event of that type was recorded among the participants represented in the summary. It does not rule out events that could occur in a larger group or under different circumstances. The registry record does not give further details about adverse-event definitions, collection methods, observation duration, or whether any events were assessed as related to the intervention. The figures should therefore be read as limited descriptive safety information, not as a comprehensive evaluation.

The primary endpoint includes a pathologic airway response such as laryngospasm, while the adverse-event summary is a separate registry outcome. The record does not provide enough detail to determine how the endpoint and adverse-event reporting categories were operationally linked. Readers should not infer that the zero adverse-event counts provide additional proof of primary endpoint success beyond the posted endpoint results.

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

The posted primary results show that all 10 participants in each group met the registry’s definition of extubation success immediately after extubation. The reported risk difference is 0.0. This is a straightforward description of the observed participants: no difference in the primary success count appears in the posted data.

That result does not demonstrate that the strategies are equivalent, that their success probabilities are identical, or that either approach is better. A small trial with no observed primary failures cannot reliably characterize uncommon failures or rule out differences that might be present in a larger population. The reported interval of 0.0 to 0.0 should not be treated as removing that uncertainty, particularly because the registry does not report how the interval was calculated.

The secondary results describe anesthetic vapor concentration at extubation. They show a difference in the group summaries, but they do not show that this difference produced the primary outcome pattern. The registry does not report an analysis linking the concentration measure to success at the participant level, and the secondary p-value is unadjusted. The secondary comparison therefore provides a descriptive result with limitations on how strongly it can support a broader conclusion.

The zero adverse-event and death counts are also limited observations from the trial participants. They do not establish the absence of risk. Details on adverse-event definitions and follow-up are not reported in the registry record.

Overall, the trial record supports a narrow account of what was observed in these groups. It does not provide a basis for medical advice or a general recommendation. Important context—including eligibility, analysis populations, missing-data handling, a full statistical plan, and the rationale for enrollment—is not reported in the registry record. Those gaps constrain interpretation beyond the posted counts and summaries.

15. Why This Trial Matters Statistically

This trial illustrates how a result can look simple at the level of the observed counts while remaining uncertain as evidence about a broader population. Both groups have the same primary success count, and the reported risk difference is 0.0. Yet the absence of observed failures among 10 participants per group does not show that failure cannot occur or that the underlying probabilities must be equal. The distinction between a sample result and a population conclusion is central to interpreting small clinical trials.

It also highlights why confidence intervals need to be considered with their method and the data structure in mind. A zero-width interval for the primary comparison may appear unusually definitive, but the registry does not state how it was constructed. Readers should not confuse a reported interval with certainty about the true effect. Sparse binary outcomes can leave important uncertainty even when the observed proportions match exactly.

The secondary outcome offers a separate statistical lesson. Its posted group means differ, and its unadjusted p-value is small, but the registry does not report the analysis hierarchy or a multiplicity plan. A numerical result can be striking without answering the primary question or establishing a causal pathway. Its role depends on the full outcome plan and analysis context, neither of which is fully documented.

Finally, the planning illustration shows why sample-size calculations should be separated from the trial’s actual design rationale. Calculations based on the observed effect and very low observed variability can produce extremely small planning figures. Such figures are not observed power, do not explain the original enrollment decision, and should not be treated as a design recommendation. The registry does not report the trial’s own sample-size justification.

16. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is the small number of participants: the record reports 20 enrolled, with 10 participants in each displayed group. The primary outcome has no observed failures, so the trial provides limited information about the frequency of failures or about differences that might emerge in other participants. The zero-width primary interval also warrants caution because its calculation method is not reported.

The registry describes the study as randomized and unmasked but does not report randomization procedures, allocation concealment, or details of outcome assessment. It does not give participant eligibility criteria or further population characteristics. This limits assessment of how broadly the findings might apply and how the trial was conducted in practice.

Analysis details are sparse. The record does not report a statistical analysis plan, the primary confidence-interval method, the analysis population, missing-data procedures, participant flow, or the handling of protocol deviations. It also does not report how the three listed outcome measures were prioritized, or provide results for more than one secondary outcome. The secondary p-value is unadjusted, and the registry does not describe a multiplicity strategy.

The secondary measure has very low reported variability, including a standard deviation of 0.0 in Group 1. This affects how the observed contrast is represented in inferential and planning calculations. The sample-size illustration uses the observed effect, but the registry does not report the trial’s own sample-size justification. The illustration cannot fill that gap.

Safety information is also limited to the posted zero counts. Definitions, collection procedures, and observation duration for adverse events are not reported in the registry record. These limitations do not invalidate the posted figures; they define the boundaries of what can be concluded from them.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Investigation of Pupillometry as Guide for Extubation Readiness in Anesthetized Children — NCT04947397.
• Registry record last updated 2025-01-22; status last verified 2024-12.
• Results first posted 2025-01-22.
• 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.

20. Record Summary

The registry record identifies NCT04947397 as “Investigation of Pupillometry as Guide for Extubation Readiness in Anesthetized Children.” It lists a randomized, parallel-group study with no masking, sponsored by the University of California, San Francisco. Enrollment is 20, the status is completed, and the phase is listed as NA. The recorded start date is 2022-06-20, and the primary completion date is 2023-02-01.

The primary endpoint is extubation success immediately after extubation. The posted results show 10 successful participants in each group and a risk difference of 0.0. The secondary outcome with posted results is anesthetic vapor concentration at extubation. The registry lists three outcome measures, but results include one secondary outcome. Serious adverse events, other adverse events, and deaths are reported as zero in both groups.

The record does not report a full statistical analysis plan, missing-data procedures, analysis populations, multiplicity methods, or the trial’s sample-size justification. These omissions should be kept in view when interpreting the posted results.