The Effect of Depth of Anesthesia as Measured by Bispectral Index (BIS) on Emergence Agitation in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Depth of Anesthesia as Measured by Bispectral Index (BIS) on Emergence Agitation in Children (NCT00990769), a randomized na study. The primary outcome is Peak Pediatric Assessment of Emergence Delirium (PAED) Score Within the First 30 Minutes of Reaching the Recovery Room (Post-Anesthesia Care Unit).

2. Clinical Question

The central statistical question is whether the average peak PAED score differed between the randomized groups. The PAED outcome is a continuous score, so the posted group means and standard deviations describe average scores and their variability. A mean difference provides a direct comparison, while its confidence interval conveys how uncertain that estimate is in light of the observed data.

The study record describes random assignment and double masking, but does not report the precise randomization procedure, allocation concealment, or who was masked. Those details matter to understanding how assignment and outcome assessment were protected from bias; they cannot be inferred from the labels alone. The record identifies Duke University as sponsor and lists the study status as completed.

The result addresses the recorded endpoint and timeframe, rather than every possible aspect of recovery or anesthesia. Secondary outcomes included time to emergence and a FLACC pain score, but the primary question remains the comparison of peak PAED scores. The statistical evidence should therefore be read as evidence about the reported measure in these groups, with attention to uncertainty and the limits of what the registry record documents.

3. Trial Design

The registry record describes a randomized, double-masked, parallel-group trial with an enrollment of 40. Its listed phase is NA. The study concerned children age 2 - 8 years old having ophthalmologic surgery under general anesthesia. Recruitment began in 2009-09, primary completion was recorded in 2010-09, and the study status is completed. These dates describe the record; they do not supply details about the conduct or timing of individual assessments.

Participants were allocated to one of two depth targets. In the high-normal BIS group, anesthesia depth was titrated to BIS 55-60 and described as lighter anesthesia. In the low-normal BIS group, depth was maintained at BIS 40-45 and described as deeper anesthesia. The listed intervention type is OTHER, with the intervention named depth of anesthesia. The registry record does not describe the precise allocation sequence generation or concealment procedure, so the mechanics of randomization are not reported in the registry record.

The primary measure was peak Pediatric Assessment of Emergence Delirium score within 30 minutes of arrival in the recovery room. The record also lists time to emergence from anesthesia and FLACC pain score as secondary outcomes. These are distinct measures of recovery and pain; the record does not establish that they were part of a single combined outcome.

The parallel randomized design supports a between-group comparison, but the interpretation depends on the conduct and analysis details available. The record says all patients in each group were analyzed for the primary endpoint. It does not report a detailed participant-flow account, a specific missing-data approach, the original sample-size justification, or a full prespecified statistical analysis plan. Randomized and double-masked are useful design descriptions, but they do not resolve those unreported details.

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: Fifty-seven patients were approached for participation; of these, fourteen declined and three were unable to participate due to surgery cancellation or rescheduling.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients in each group were analyzed.

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 Peak Pediatric Assessment of Emergence Delirium (PAED) Score Within the First 30 Minutes of Reaching the Recovery Room (Post-Anesthesia Care Unit), measured over Within 30 minutes of arrival in recovery room.

The primary endpoint is the peak Pediatric Assessment of Emergence Delirium score recorded within 30 minutes of arrival in the recovery room. The PAED measure is described as a validated observational assessment of five aspects of behavior during emergence from anesthesia: caregiver eye contact, purposeful movement, evidence of awareness of surroundings, restlessness, and inconsolability. Ratings are summed into a score from 0 - 20, with higher values indicating greater severity of emergence agitation.

The endpoint is relevant to the stated research question because it quantifies observed agitation during the specified recovery period. Using the peak score focuses on the highest recorded score in that period rather than an average across repeated observations. The registry record does not state how often observations were made, who made the ratings, or how disagreements between observers were handled. Those procedures can affect measurement consistency and are not reported in the registry record.

For a continuous score, the group mean describes the average observed score, and the standard deviation describes the spread of individual scores around that average. Neither quantity alone describes the full score distribution. The comparison of means provides a concise summary of the difference in average scores between the two target groups, while the confidence interval indicates the range of differences compatible with the reported estimate under the calculation’s assumptions.

The endpoint is not a direct measurement of every dimension of emergence or later recovery. It is an observational scale, tied to a particular assessment period and behaviors. Conclusions about this endpoint should therefore remain specific to peak PAED score within the recorded recovery-room timeframe.

7. Results Posted in the Registry

• Low-normal BIS: mean 6.70 versus 8.60 on control; difference -1.90 (95% CI -4.97 to 1.17), standardized effect d = -0.38; z-test p = 0.225.

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.

Time to Emergence From Anesthesia

• 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:
  • Low-normal BIS: mean 12.00 versus 14.00 on control; difference -2.00 (95% CI -4.79 to 0.79), standardized effect d = -0.44; z-test p = 0.160.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low-normal BIS and the control. The interval gives the range of effects that remain compatible with the data.

Pain Score: Faces, Legs, Activity, Cry, and Consolability (FLACC)

• 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:
  • Low-normal BIS: mean 3.50 versus 5.30 on control; difference -1.80 (95% CI -4.03 to 0.43), standardized effect d = -0.51; z-test p = 0.114.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Low-normal BIS and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover time to emergence from anesthesia and FLACC pain score within 30 minutes of arrival in recovery. Their posted means follow a direction in which the low-normal BIS group has lower averages than the high-normal BIS group, as do the primary group means. The uncertainty intervals for the recalculated secondary comparisons include zero, and their unadjusted p-values do not meet a conventional significance threshold. The endpoint-specific numerical details are best read alongside their own units, timeframes, and intervals rather than treated as a single combined result.

This broad directional pattern is consistent with, but does not independently confirm, the primary comparison. Secondary outcomes address different aspects of recovery and are not interchangeable with peak PAED score. A pattern in the same direction across outcomes can be descriptive, but it does not establish a common underlying effect or a causal mechanism. The registry record does not report a joint analysis of these outcomes.

Secondary findings generally carry less confirmatory weight when multiple outcomes are examined without a reported adjustment or prespecified hierarchy. Each additional comparison creates more opportunity for a nominally notable result to occur by chance. Here, the secondary p-values are explicitly unadjusted in the recalculations. The multiplicity plan and any correction for testing several outcomes are not reported in the registry record, so these findings should be treated as exploratory rather than as separate definitive tests.

The registry lists two secondary outcomes, while the overall record includes three outcome measures. It does not report whether there were additional analyses or endpoints that were considered but not posted. The secondary results can provide context about recovery, but they do not remove uncertainty in the primary result and should not be used to turn an inconclusive primary comparison into a definitive conclusion.

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

• Time to Emergence From Anesthesia
• Pain Score: Faces, Legs, Activity, Cry, and Consolability (FLACC)

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference represent?

For a continuous outcome, a mean difference compares the average score in one group with the average score in another. The recalculated contrast is defined as low-normal BIS minus high-normal BIS. Under that ordering, the estimate is -1.9 PAED units: the posted average in the low-normal group is lower. Reversing the order reverses the sign but not the magnitude. The sponsor’s reported value of 1.9 is consistent with the reverse ordering. Group order is therefore essential when interpreting a signed difference.

A mean difference is expressed in the original outcome units, which in this case are units on the PAED scale. It is not a percentage change and does not describe each participant’s score. Individuals may have scores above or below their group average. The standard deviations of 5.3 and 4.6 show that observed scores varied within both groups; a group mean does not capture that individual variation.

What does a confidence interval add?

A confidence interval gives a range of estimates compatible with the observed data under the method’s assumptions. The recalculated 95% interval for the low-normal minus high-normal comparison runs from -4.969 to 1.169. Because this range crosses zero, the data are compatible with a negative difference, no difference, or a positive difference. It does not mean there is a 95% probability that the true value lies in this particular computed interval. In general, confidence intervals reflect sampling uncertainty under a repeated-sampling framework and the assumptions of the calculation.

The unadjusted p-value of 0.225 measures how unusual the data would be under a specified null hypothesis of no group difference and the test assumptions. It is not the probability that the null hypothesis is true, nor a measure of the probability that the finding is due to chance. A p-value above a conventional threshold does not demonstrate equivalence. To establish equivalence or rule out differences considered important, an appropriate margin and design would be needed; neither is reported in the registry record.

Why use a t-test?

The sponsor reports a two-sided t-test comparing final values. A t-test evaluates whether the data are compatible with a difference in group means, accounting for the variability and amount of information in the groups. “Two-sided” means departures in either direction are considered, rather than only a prespecified increase or decrease. The record does not report additional details about the exact variance assumptions or whether any covariate adjustment was used, so those aspects are not reported in the registry record.

The recalculation uses the posted group means, standard deviations, and group sizes to form an unadjusted comparison. It does not incorporate participant-level data, covariates, repeated observations, or corrections for multiple outcomes. The estimate and interval should therefore be understood as a simple summary-based calculation, not as a reconstruction of every feature of the trial’s original analysis.

What does variability imply?

Standard deviation describes the spread of participant scores around a group mean. It is different from the standard error, which describes uncertainty in an estimated mean. A wide spread can make a group mean less precise, particularly when information is limited. The mean and standard deviation alone do not reveal skewness, outliers, or other features of the distribution. The registry record does not provide participant-level scores or a distribution plot in the registry record described for this interpretation.

In general, over-dispersion matters when the observed variability is greater than assumed by a statistical model. If a model understates variability, standard errors may be too small and inferential results may appear more precise than justified. The posted analysis is a comparison of continuous means, and no over-dispersion issue is reported for this trial; this general point should not be mistaken for a finding about these data.

How should the recalculation be distinguished from the trial analysis?

The sponsor’s analysis is the reported trial analysis: a two-sided t-test with a mean difference of 1.9 and p > 0.05. The posted registry information does not give a confidence interval for that result. The separate recalculation uses summary statistics and reports the contrast in the opposite order, along with a 95% confidence interval and unadjusted p-value. Since the registry comparison does not flag a discrepancy, the two descriptions are not in conflict on the broad inference; their signed estimates reflect opposite contrast ordering.

Recalculated results are useful for transparent interpretation, particularly when a posted estimate lacks interval limits. However, summary-based calculations may not reproduce details that depend on the original participant-level data or a fuller analysis plan. In general, a trial’s prespecified and reported analysis takes precedence over a simple recalculation when they differ. No discrepancy is indicated in this record.

What can and cannot be inferred?

The results describe evidence about average PAED scores for the randomized groups and the specified time window. They do not determine whether a difference is important to patients or caregivers, because an interpretation threshold is not reported in the registry record. They also do not prove that the groups have identical outcomes. Statistical uncertainty, the measurement process, and limits in documentation all matter when translating a numerical comparison into a substantive conclusion.

11. Confidence Intervals and Precision

The recalculated mean difference for peak PAED score is -1.9 for low-normal BIS minus high-normal BIS, with a 95% confidence interval from -4.969 to 1.169. The interval spans zero. Thus, the observed data are compatible with a range of contrasts in both directions, including no average difference. The interval should be considered together with the point estimate; reporting only the estimate would conceal the substantial uncertainty around it.

In general, a confidence interval is more informative than a significance label alone because it displays both the direction and the range of plausible values under the calculation’s assumptions. Here, the interval is not narrow enough to identify a precise effect size. It does not establish equivalence, and its limits do not automatically define what would be clinically meaningful. The registry record does not report a clinically important difference threshold or an equivalence margin.

The sponsor reports p > 0.05 for the two-sided t-test but no confidence limits for that result. The recalculated interval comes from the posted group summaries and is unadjusted. It is useful for describing precision, but it should not be confused with a sponsor-reported interval or a participant-level adjusted estimate.

Precision is also distinct from validity. A narrow interval would not by itself address possible measurement bias, incomplete reporting, or generalizability; a wide interval does not show that the treatment targets are equivalent. The registry states that all patients in each group were analyzed for the primary outcome, but details of missing observations and data handling are not reported in the registry record. Those omissions limit how fully the reported precision can be assessed.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the original trial’s design calculation. The entries are participants per arm for 80% power and participants per arm for 90% power. They are not total sample sizes or total events. The stated planning assumptions are a two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original design assumptions, including any original target power or effect-size justification, are not reported in the registry record.

In plain terms, the 80% power column gives an illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is present. The 90% power column uses a higher target chance of detecting that effect. These are design calculations, not evidence about what the completed trial achieved. They do not give the probability that the observed result is true, and they are not observed power.

The rows for planning for 100%, 75%, and 50% of the observed effect illustrate how the assumed target size changes the planning requirement. Smaller effects need more participants to detect under otherwise unchanged assumptions, so the smaller-effect rows have larger per-arm requirements. The curve presents the same planning relationship visually and should be read as an illustration of assumed effect size and required enrollment, not as a new outcome result.

These planning values use the observed effect as their starting point, which is uncertain in a small study. They should not be interpreted as a definitive recommendation for a future trial. A design would require a justified target effect, endpoint assumptions, and an analysis plan; those original design details are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.900; pooled standard deviation σ = 4.999.
2. n = 2 × (1.96 + 0.842)² × 4.999² / -1.900² = 108.7, rounded up to 109 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.9                      # observed difference in means
sigma <- 4.99897357885649                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(990769)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 109 (80% power), 146 (90% power)
 75% of observed effect: n per arm = 194 (80% power), 259 (90% power)
 50% of observed effect: n per arm = 435 (80% power), 582 (90% power)
power.t.test: 109.6 
Simulated power at n = 109 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor reports a two-sided t-test for final values, with a mean difference of 1.9 and p > 0.05. The registry record does not report a confidence interval for the sponsor’s estimate. The recalculation gives a mean difference of -1.9 for low-normal BIS minus high-normal BIS, with a 95% confidence interval from -4.969 to 1.169 and an unadjusted p-value of 0.225.

The signs differ because the contrasts are ordered in opposite directions: the sponsor’s positive 1.9 corresponds in magnitude to the recalculated negative 1.9. The registry comparison does not flag a discrepancy. Both presentations indicate that the reported comparison did not cross the stated conventional significance threshold, while the recalculation makes uncertainty visible through an interval that includes zero.

The sponsor’s own analysis remains the primary reported inferential result. The recalculation is an unadjusted check derived from posted group summaries; it cannot account for any analysis features not represented in those summaries. The record does not report sufficient detail to determine whether additional adjustments were part of the sponsor’s analysis. The recalculation therefore complements, rather than replaces, the sponsor’s reported test.

Neither result demonstrates that the groups are equivalent. The sponsor’s p-value and the recalculated interval address evidence for a difference under their respective methods; they do not establish the absence of a potentially meaningful difference. No equivalence margin or clinical interpretation threshold is reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary PAED outcome and secondary outcomes for time to emergence and FLACC pain score. It reports one analysis for the primary comparison, but does not provide a complete statistical analysis plan or a multiplicity strategy. It is therefore not reported in the registry record whether the primary endpoint was tested within a prespecified hierarchy, whether secondary endpoints were formally confirmatory, or whether adjustments were planned for multiple comparisons.

In general, multiplicity arises when several hypotheses or outcomes are tested. Considering many unadjusted tests increases the chance that at least one result appears statistically notable even if there is no true effect across the outcomes. This is why secondary findings with unadjusted p-values should be interpreted cautiously. The registry’s posted secondary recalculations are unadjusted, and no correction is described in the record. This is a limitation in what can be inferred from the collection of outcomes, not evidence that the results are wrong.

The primary endpoint description states that all patients in each group were analyzed. The registry does not give a detailed account of missing endpoint values, withdrawals, exclusions, or how missing observations were handled. It also does not report whether the analysis followed intention-to-treat principles or how adherence to assigned BIS targets was evaluated. These details are not reported in the registry record, and it is not appropriate to assume a particular approach.

Randomization can support a fair comparison when analyzed appropriately, but the analysis population and handling of missing data affect the meaning of that comparison. Without a participant-flow account or details of missing-data procedures, readers cannot assess whether the analyzed groups fully correspond to all randomized participants or whether missing observations could have influenced the estimates.

Likewise, the record does not describe interim analyses, stopping rules, or the original statistical plan. Those details are not reported in the registry record. Their absence from the registry should be treated as an information gap, not as proof that the procedures were or were not used.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event record lists zero serious adverse events in the high-normal BIS group among 22 at risk, and zero in the low-normal BIS group among 18 at risk. It also lists zero other adverse events in the high-normal group among 22 at risk and zero in the low-normal group among 18 at risk. These are the counts posted for the recorded categories and groups.

A zero count in a registry entry means that no events are reported for that category in the displayed record; it does not establish that there was no possibility of harm, nor does it demonstrate equivalent safety between groups. The study was small, and event counts alone do not quantify the precision of safety comparisons. The registry record does not provide a detailed adverse-event narrative, event definitions, or a broader assessment of safety outcomes.

Death counts are not reported in the registry record. No top serious adverse-event terms are listed. The absence of listed terms should not be interpreted as a comprehensive account of every possible event beyond what the record reports. Safety interpretation should remain limited to these posted counts and their recorded categories.

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

The posted primary results show average peak PAED scores of 8.6 in the high-normal BIS group and 6.7 in the low-normal BIS group. The recalculated contrast, low-normal minus high-normal, is -1.9, with a 95% confidence interval from -4.969 to 1.169 and an unadjusted p-value of 0.225. The sponsor’s own two-sided analysis reports a mean difference of 1.9 and p > 0.05. The signs reflect opposite group ordering, and neither analysis provides clear statistical evidence of a difference at the conventional threshold.

This does not mean that the anesthesia targets produce identical PAED scores. The confidence interval includes zero but also includes differences in either direction. The result leaves meaningful uncertainty about the size and direction of any group difference. The record does not report an equivalence margin or threshold for a clinically important difference, so the analysis cannot establish equivalence or determine clinical importance.

Nor should the observed group means be treated as a causal answer independent of design and measurement. The study is described as randomized and double-masked, but details of allocation, masking implementation, outcome assessment, missing data, and adherence are not reported in the registry record. These information gaps constrain how fully the result can be evaluated.

The finding is specific to children age 2 - 8 years old undergoing ophthalmologic surgery under general anesthesia, the two recorded BIS targets, and peak PAED score within 30 minutes of recovery-room arrival. It does not automatically generalize to other ages, procedures, anesthesia approaches, or outcome timeframes. The secondary results provide additional descriptive context but do not change the uncertainty in the primary comparison.

In general, a non-significant result is not proof of no effect. It indicates that the analysis did not provide sufficiently strong evidence against the null hypothesis under the method used. The appropriate reading is therefore a statistically inconclusive comparison with a broad interval, rather than a claim that one target is better, worse, or the same.

18. Why This Trial Matters Statistically

This trial illustrates why clinical trial results should be read through both the estimated contrast and its precision. The group means alone point to a lower observed average PAED score in the low-normal BIS group, but the confidence interval extends across zero and allows differences in either direction. A directional pattern is not enough to establish a reliable group difference.

It also demonstrates the importance of stating contrast orientation. The sponsor’s reported difference is positive, while the recalculation is negative, because the groups are subtracted in opposite orders. Without clear labels, readers could mistake a sign reversal for a disagreement in results. Once the ordering is recognized, the estimates correspond in magnitude.

The distinction between a reported analysis and a summary-based recalculation is another useful statistical lesson. A recalculation can make an interval available from posted means, standard deviations, and group sizes, but it cannot reproduce unreported features of the original analysis. The sponsor’s own test and the unadjusted summary-based result should be presented as related but not interchangeable evidence.

Finally, the trial shows why absence of statistical significance should not be equated with equivalence, and why planning illustrations should not be confused with observed power. The uncertainty in a small study can remain substantial even when the point estimate is easy to state. Readers need the outcome definition, comparison direction, interval, and reporting limitations together to understand what the trial does and does not establish.

19. 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 posted sample is limited, with group sizes of 22 and 18. The primary interval is broad and crosses zero, leaving considerable uncertainty about the magnitude and direction of the mean difference. The registry record does not report an equivalence margin or clinically important difference threshold, so the result cannot be judged against such a criterion.

Important design and analysis details are not reported in the registry record. These include the method for generating and concealing the allocation sequence, how double masking was implemented, how outcome assessors were trained, and whether PAED observations were repeated at a specified frequency. The record also does not describe adherence to the assigned BIS ranges or how deviations were handled.

The endpoint is an observational score over a defined recovery-room period. The record does not report who rated behavior, whether ratings were independent, or how missing or ambiguous ratings were handled. The reported statement that all patients in each group were analyzed does not substitute for a detailed participant-flow description or an account of missing values.

The sponsor’s reported analysis gives no confidence limits in the registry record. The available recalculation is unadjusted and uses posted summary statistics, so it may not reflect analyses using participant-level information or covariate adjustment. The original statistical analysis plan, sample-size rationale, interim analyses, and multiplicity strategy are also not reported in the registry record.

Generalizability is bounded by the study population and setting described: children age 2 - 8 years old having ophthalmologic surgery under general anesthesia. The record does not establish that the results apply to other procedures, ages, or settings. These limitations concern the available evidence and documentation; they do not establish that any unreported procedure was absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: The Effect of Depth of Anesthesia as Measured by Bispectral Index (BIS) on Emergence Agitation in Children — NCT00990769.
• Registry record last updated 2013-05-31; status last verified 2013-05.
• Results first posted 2013-05-31.
• 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.

23. Record Summary

The registry record describes a completed, randomized, double-masked, parallel-group study sponsored by Duke University. It enrolled 40 children undergoing ophthalmologic surgery under general anesthesia, comparing a high-normal BIS target of 55-60 with a low-normal BIS target of 40-45.

The primary outcome was peak PAED score within 30 minutes of recovery-room arrival. The group means were 8.6 and 6.7, respectively. The sponsor reported a two-sided t-test with mean difference 1.9 and p > 0.05. An unadjusted recalculation using low-normal minus high-normal gives -1.9, with a 95% confidence interval from -4.969 to 1.169 and p-value 0.225.

The interval includes zero and does not establish a clear average difference or equivalence. Secondary outcomes concerned emergence time and FLACC pain score. The registry reports zero serious and other adverse events in each group’s listed at-risk counts; death counts are not reported in the registry record. Several details of trial conduct, missing-data handling, and the original analysis plan are not reported in the registry record.