This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Performance Evaluation of the Depth of Anesthesia Monitors in Pediatric Surgery (NCT02240368), a registered phase not stated study. The primary outcome is BISPECTRAL Index.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02240368 |
| Phase | Phase not stated |
| Condition | Anesthesia, Child |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Foggia |
| Results posted | Yes |
2. Clinical Question
Population
Children undergoing surgery with general anesthesia, divided into age groups: Group 1, children age between 1 month to 12 months; Group 2, children age between 13 months and 36 months; and Group 3, children age between 37 months to 144 months.
Intervention
The study evaluates BIS and Entropy EEG depth-of-anesthesia monitors. The registry record does not describe a treatment intervention assigned to participants.
Comparator
The monitor readings are considered in relation to one another and to end-tidal sevoflurane concentration, abbreviated ETsevo. The age groups are not like-for-like control groups, and allocation is not stated.
Primary question
How well do BIS readings track ETsevo during anesthesia, and how does that relationship vary across pediatric age groups? The broader study purpose also asks how BIS and Entropy agree between themselves and with ETsevo in relation to age.
The registry describes a measurement-performance question rather than a comparison of assigned treatments. Its focus is whether monitor values correspond to a reference measure of anesthetic exposure over the course of anesthesia, and whether age is relevant to that correspondence. The primary outcome description specifies a prediction probability for agreement between BIS and ETsevo within each group. The registry also lists awakening outcomes for BIS and Entropy.
This question matters statistically because a monitor reading is useful as an indicator only to the extent that it tracks the state or reference measure of interest. Agreement or association between measurements does not by itself establish that one monitor is better for patient outcomes. Numerical estimates of monitor performance, and the precision of those estimates, are not reported in the registry record.
3. Trial Design
The record describes a completed study sponsored by the University of Foggia, with enrollment of 50. Its recorded start was 2014-09 and its primary completion was 2014-12. The stated setting is pediatric surgery, and the study purpose concerns BIS and Entropy EEG monitor performance in relation to end-tidal sevoflurane concentration and age.
Participants are arranged in three age groups: Group 1 covers children age between 1 month to 12 months; Group 2 covers children age between 13 months and 36 months; and Group 3 covers children age between 37 months to 144 months. These are age-defined groups, not treatment and control arms. The registry record does not state how participants were allocated, and it does not describe a randomized comparison. The groups therefore should not be interpreted as randomized, like-for-like controls.
The primary outcome is titled BISPECTRAL Index. Its description says BIS and ETsevo values are used to generate a prediction probability of agreement over the period of anesthesia for each group. The outcome timeframe describes BIS values from induction to awakening, collected at a 1/5 sec sampling rate over an average of 1 hours. The registry also lists BISPECTRAL Index Awaking and Entropy Awaking as secondary outcomes. It records 4 outcome measures and 4 analyses, but does not provide enough detail to characterize every analysis.
Eligibility criteria, recruitment procedures, the number enrolled in each age group as a design characteristic, and the statistical analysis plan are not reported in the registry record. The record does not explain the rationale for the enrollment target or report a sample-size justification.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| STARTED | 9 | 22 | 19 |
| COMPLETED | 8 | 22 | 18 |
| NOT COMPLETED | 1 | 0 | 1 |
Reasons for not completing this period:
| Reason | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| Surgery lasted less then 20 minutes | 1 | 0 | 0 |
| Entropy failed to detect more than 50% | 0 | 0 | 1 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|---|
| Participants analysed | 8 | 22 | 18 | 48 | |
| Age, Categorical: <=18 years | Participants | 8 | 22 | 18 | 48 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | months | 6.63 (SD 3.7) | 24.95 (SD 8.0) | 82.22 (SD 33.8) | 43.38 (SD 37.56) |
| Sex: Female, Male: Female | Participants | 4 | 8 | 9 | 21 |
| Sex: Female, Male: Male | Participants | 4 | 14 | 9 | 27 |
| Region of Enrollment: Italy | participants | 8 | 22 | 18 | 48 |
6. Primary Endpoint
The registry lists the primary outcome as BISPECTRAL Index, measured over BISPECTRAL index values from the induction moment to the awakening moment, 1/5 sec sampling rate, an average of 1 hours.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled BISPECTRAL Index and is expressed in units on a scale. The endpoint description focuses on prediction probability, written as PK in the registry, for agreement between BIS and end-tidal sevoflurane concentration across the period of anesthesia, calculated for each age group. End-tidal sevoflurane is the measured concentration of sevoflurane at the end of exhalation, used in this study as a reference alongside the monitor readings.
Prediction probability is described in the registry as a measure suited to assessing anesthetic-depth indicators. In general, it evaluates how well an indicator’s values correspond to observed depth or a reference measure, without depending on the indicator’s scale units or on a particular underlying distribution. It is therefore intended to describe tracking performance, not a clinical outcome such as recovery or complications.
The stated measurement window runs from induction to awakening, with BIS values collected at a 1/5 sec sampling rate over an average of 1 hours. The registry’s primary outcome description specifically names BIS and ETsevo; it does not provide a numerical endpoint estimate. Although the broader study purpose mentions both BIS and Entropy, the primary endpoint description does not specify an Entropy-versus-ETsevo estimate. The registry record does not report the endpoint’s numerical results or confidence intervals.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question and measurement approach, but it does not report numerical findings for the primary endpoint. Consequently, it is not possible to describe the observed prediction probability, its uncertainty, or whether the estimates differed across age groups. The record also does not state a result for agreement between BIS and Entropy. Any conclusion about the degree of monitor tracking or age-related variation would require results that are not reported in the registry record.
The endpoint is a measure of how monitor readings correspond to ETsevo during anesthesia. In general, a prediction-probability estimate describes ranking or correspondence between an indicator and a reference; it does not mean the monitor directly measures anesthetic concentration or that the two quantities are interchangeable. Nor does an association establish that monitor-guided decisions improve patient outcomes. The record focuses on monitor performance, not on a randomized comparison of care strategies.
A confidence interval, in general, communicates the precision of an estimate: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The primary outcome lists a 95% confidence interval as its dispersion measure, but the interval limits are not reported in the registry record. Without those limits, the precision of any group estimate cannot be assessed from this record.
The age groups provide a way to examine whether the monitor-reference relationship varies across pediatric ages. They do not, by themselves, establish that age causes any difference. Age groups can differ in other characteristics, and the registry record does not report adjustment methods or details needed to evaluate potential confounding. Because allocation is not stated and the groups are not a randomized control comparison, differences between groups should not be treated as causal treatment effects.
The adverse-event record lists 0 serious adverse events and 0 other adverse events for each group, with the corresponding at-risk counts recorded separately. These entries describe the registry’s reported counts; they do not demonstrate that no events could occur or establish a broad safety profile. The record does not report deaths, ascertainment details, or the observation period for adverse events.
Overall, the record supports a description of the study question, age grouping, and intended measurement framework. It does not support a conclusion about the strength of BIS or Entropy tracking, differences by age, or clinical benefit. The numerical endpoint results and their precision are not reported in the registry record.
9. Statistical Methods Explained
The registry describes prediction probability as the principal statistical measure for assessing BIS performance against ETsevo. It states that the measure quantifies correlation between observed anesthetic depth and indicator values, and that it is nonparametric and independent of scale units and assumptions about underlying distributions. The endpoint description says BIS and ETsevo values generate a prediction probability for each age group over the anesthesia period.
What does prediction probability describe?
In general, prediction probability assesses whether an indicator’s ordering of observations corresponds to the ordering of a reference measure or observed state. It is useful when the scientific question concerns tracking or ranking rather than a direct, unit-for-unit comparison. A nonparametric measure does not require the same distributional assumptions as methods based on a specified parametric model. This does not make the measure assumption-free: the way observations are selected, paired, and analyzed still matters.
In this study, the relevant pairing is between BIS readings and ETsevo during anesthesia. The endpoint description does not provide the estimator’s implementation details, including how repeated observations within a child were handled or how the group-level confidence intervals were constructed. Those details are not reported in the registry record. The record’s general definition should therefore not be taken as a complete statistical analysis specification.
Why is the confidence interval relevant?
The endpoint names a 95% confidence interval. In general, a confidence interval represents uncertainty around an estimate under the assumptions of the method used to calculate it. It helps distinguish a relatively precise estimate from one with substantial uncertainty. It is not a guarantee that the true value lies in the interval, and its width is influenced by the amount and structure of information available.
Repeated measurements can contribute information about patterns over time, but measurements from the same child are usually related rather than independent. In general, treating correlated repeated observations as independent can make standard errors too small and intervals too narrow. Appropriate analysis may account for within-person dependence, but the registry record does not report whether or how that was done. The sampling schedule is described as 1/5 sec, and the outcome period extends from induction to awakening; those details make the handling of repeated measurements important to understanding precision.
What does over-dispersion mean in general?
Over-dispersion occurs when observed variability exceeds what a statistical model assumes. If a model does not accommodate that extra variability, uncertainty can be understated. This is a general consideration for statistical modeling, not a reported feature of this study. The registry record does not identify a model for over-dispersion, nor does it report a model-based analysis plan. The nonparametric description of prediction probability should not be confused with a statement that every source of dependence or variability has been addressed.
How should the age groups be compared?
The record specifies three age-defined groups and describes a group-specific prediction probability. In general, estimates across groups can be compared descriptively, but a difference between estimates is not automatically evidence of an age effect. A formal comparison requires a defined contrast and an uncertainty estimate for that contrast. The registry record does not report a specific hypothesis test or adjustment strategy for comparing age groups. It also does not describe adjustment for other participant or procedural characteristics.
The groups are not described as randomized treatment arms, and allocation is not stated. Thus, the design should not be interpreted as a trial comparing monitor-guided interventions. The estimates address monitor-reference correspondence within age groups, rather than the effect of assigning one monitoring approach instead of another.
What do the planning illustrations mean?
In general, a sample-size illustration based on an observed effect asks how much information a future study might need to detect an effect of a specified fraction of that observed effect, under stated assumptions. It is a planning exercise, not evidence that the current study had a particular probability of detecting an effect. The assumptions described for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These illustrations are not the trial’s own design justification. The registry record does not report the numerical planning results or a sample-size justification for this study. No planning illustration should be read as observed power.
More broadly, the registry identifies 4 outcome measures and 4 analyses, but the available description does not map all analysis procedures to specific estimates. The actual analysis plan, methods for handling missing observations, and any sensitivity analyses are not reported in the registry record. Those omissions limit independent assessment of how the intended endpoint was estimated.
10. Multiplicity, Missing Data and Analysis Populations
The registry records 4 outcome measures and 4 analyses. It names BISPECTRAL Index as the primary outcome and lists BISPECTRAL Index Awaking and Entropy Awaking among the secondary outcomes. The broader study purpose also concerns agreement between BIS and Entropy and their relationships with ETsevo. The record does not identify all analysis hypotheses or state whether a multiplicity adjustment was planned.
Multiplicity matters when several outcomes, groups, or statistical comparisons are examined. In general, the more inferences considered, the greater the chance that at least one result may appear notable by chance if each is judged without accounting for the set of comparisons. Adjustment methods can address this issue, but they also depend on which tests are considered part of the same family. Since the analysis plan and adjustment strategy are not reported, the registry record does not establish how multiplicity was handled.
Missing-data methods and analysis populations are not reported in the registry record. The record does not state how many participants contributed to each endpoint, whether all enrolled participants were analyzed, how missing monitor readings were handled, or whether exclusions occurred. It therefore is not possible to assess whether the reported analysis populations would differ from the enrolled population.
The registry records enrollment of 50, but that fact alone does not establish the number contributing valid observations to any particular analysis. The outcome description involves repeated readings from induction to awakening, so in general, incomplete measurement periods could affect available data. Whether that occurred, and how it was addressed, is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group 1 | 0 | 8 | 0.0% |
| Group 2 | 0 | 22 | 0.0% |
| Group 3 | 0 | 18 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1 | 0 of 8 |
| Group 2 | 0 of 22 |
| Group 3 | 0 of 18 |
The adverse-event entries report 0 serious adverse events and 0 other adverse events for Group 1, with 8 recorded at risk; 0 serious adverse events and 0 other adverse events for Group 2, with 22 recorded at risk; and 0 serious adverse events and 0 other adverse events for Group 3, with 18 recorded at risk. These are registry counts, not estimates of comparative risk.
A zero count means no events in that category are recorded for the listed group in this entry. It does not prove that the event risk is absent. In general, event counts are interpreted in relation to the group observed and the completeness and duration of follow-up. The adverse-event observation period and ascertainment procedures are not reported in the registry record, so the scope of these entries cannot be fully assessed.
No serious adverse-event terms are listed. Deaths are not reported in the registry record. These safety entries do not establish that the monitoring approaches caused or prevented events, and they do not support a comparison between age groups as if they were randomized treatment arms. The registry record gives no further detail about event definitions or individual event descriptions.
12. What the Result Does, and Does Not, Mean
This study addresses a measurement question: how BIS and Entropy EEG monitor readings correspond to ETsevo during pediatric anesthesia, and whether the relationship varies across age groups. The primary endpoint is described as prediction probability for BIS in relation to ETsevo. This can characterize monitor tracking, but it is not a direct measure of patient benefit.
The registry record does not report the numerical primary endpoint results or confidence intervals. It therefore does not show how strong the correspondence was, how precisely it was estimated, or whether it varied across the age groups. Numerical results for the broader BIS-and-Entropy comparison are also not reported. The record cannot support a conclusion that either monitor does or does not perform well.
Even if estimates were available, a measure of correspondence would not by itself show that a monitor improves clinical decisions or outcomes. Establishing that kind of effect would require evidence addressing the consequences of using the monitor, not only how its readings relate to a reference measure. This record describes no randomized comparison of monitoring strategies, and allocation is not stated.
Age-group estimates, if interpreted descriptively, would apply to the groups and setting studied. Differences between groups would not alone establish that age caused a difference, since the registry record does not report adjustment for other characteristics. Likewise, zero adverse-event counts in the registry should not be taken as proof that risk is absent; the event observation period and ascertainment methods are not reported.
The sound interpretation is therefore limited to the study’s stated aim and measurement design. The registry record identifies what the investigators intended to evaluate, but it does not report enough results to assess monitor performance, precision, age-related patterns, or clinical consequences.
13. Why This Trial Matters Statistically
This study raises a useful statistical question about measurement in a population for which the registry says monitor utility was undefined: do monitor readings track a reference measure similarly across pediatric ages? A monitor can produce a value continuously over time, but interpreting that value depends on how well it corresponds to the state or reference of interest. Assessing that correspondence is distinct from simply reporting average readings.
The design also highlights the importance of age as a possible source of variation in measurement performance. Group-specific estimates can help reveal whether a single overall summary might obscure different patterns across ages. However, the groups are age-defined rather than randomized, so estimates should be understood as descriptive comparisons unless a suitable comparative analysis is specified. The registry record does not report a formal test of differences between groups.
Methodologically, repeated monitoring produces measurements that may be dependent within a child. In general, analysis and uncertainty estimation should account for the structure of repeated observations; otherwise, precision may be overstated. The registry’s description of a 1/5 sec sampling rate and a measurement period from induction to awakening makes clear why the approach to repeated observations is important. The method used for that purpose is not reported in the registry record.
The study is also a reminder to separate a performance metric from a clinical effect. Prediction probability can describe correspondence with a reference, but it does not itself establish better care or improved outcomes. Since numerical results and analysis details are absent from the registry record, the statistical importance lies in the question and endpoint framework rather than in a result that can be evaluated from this record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record contains no numerical primary endpoint estimate or confidence interval. As a result, the central question about BIS tracking relative to ETsevo cannot be answered from the recorded results. It also does not provide numerical findings for the broader comparison involving Entropy, or a reported result on differences across age groups.
The study groups are defined by age, and the record states that allocation is not stated and that the arms are not a like-for-like control comparison. Any group differences would therefore need cautious interpretation. The registry record does not report adjustment for participant characteristics, procedure details, or other factors that could influence monitor readings or ETsevo.
The registry gives a sampling rate and a measurement window, but it does not report how repeated readings were paired or summarized, how within-child dependence was handled, or how the confidence intervals were calculated. It also does not describe handling of missing monitor readings, exclusions, analysis populations, or sensitivity analyses. These gaps prevent assessment of the robustness of the intended estimates.
Although 4 outcome measures and 4 analyses are recorded, the registry does not provide a complete statistical analysis plan or explain how multiple outcomes and comparisons were handled. The rationale for enrollment of 50 and the study’s own sample-size justification are not reported in the registry record. The safety entries list zero events, but event definitions, ascertainment, and the observation period are not stated. Together, these omissions limit interpretation of both the measurement findings and the safety record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Performance Evaluation of the Depth of Anesthesia Monitors in Pediatric Surgery — NCT02240368.
- Registry record last updated 2018-08-14; status last verified 2018-07.
- Results first posted 2015-07-09.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02240368 is a completed study sponsored by the University of Foggia, with enrollment of 50. Its recorded start was 2014-09 and its primary completion was 2014-12. The study evaluates BIS and Entropy EEG monitoring in pediatric surgery, with age-defined groups covering children age between 1 month to 12 months, 13 months to 36 months, and 37 months to 144 months.
The primary outcome is titled BISPECTRAL Index and is described as prediction probability for agreement between BIS and ETsevo over anesthesia, estimated by group. The measurement period is described as induction to awakening, with a 1/5 sec sampling rate over an average of 1 hours. Secondary outcomes include BISPECTRAL Index Awaking and Entropy Awaking.
The registry record does not report numerical endpoint results, confidence-interval limits, a complete statistical plan, missing-data methods, or analysis populations. Adverse-event entries record 0 serious and 0 other adverse events in each group. The listed groups are not randomized control comparisons.