The Influence of Age on EEG Signals and Consciousness During Anesthesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Influence of Age on EEG Signals and Consciousness During Anesthesia (NCT04765046), a na na study. The primary outcome is BIS50.

2. Clinical Question

The central scientific question concerns how age relates to EEG signals and consciousness during anesthesia, and whether collected data can support improvement of the current BIS algorithm for older adults. The registry record describes a prospective, multicenter, non-invasive, interventional data-collection study. It does not describe a randomized treatment comparison or a separate control arm. The study therefore should be read as collecting observations with the BIS system during usual elective surgery under general anesthesia, rather than testing the monitor against an assigned alternative.

The primary endpoint links the BIS index to a clinical classification of unconsciousness based on MOAA/S. It is intended to characterize a BIS value associated with that classification in half of subjects. This is a population-level summary, not a value guaranteed to classify every individual participant. Whether the endpoint differs by age, and how precisely it was estimated, cannot be determined from the registry record because the primary outcome result is not reported there.

3. Trial Design

NCT04765046 is listed as a completed prospective, multicenter, non-invasive, interventional data-collection study. Its title is “The Influence of Age on EEG Signals and Consciousness During Anesthesia,” and the official title includes the acronym TIARA. The listed condition is anesthesia. The sponsor is Medtronic - MITG. Enrollment is recorded as 90. The study start date is 2021-08-18, and primary completion is recorded as 2023-04-03.

The design is listed as single-group, with allocation marked NA and masking listed as none. The registry describes enrolled subjects undergoing standard-of-care elective surgery under general anesthesia. They were equipped with the BIS™ System to measure and interpret brain wave activity non-invasively during the surgery duration. Thus, the monitor is used for data collection within the described surgical setting; the record does not describe an assigned alternative monitor or a randomized comparison.

The outcome record lists one primary measure, BIS50, as a continuous endpoint summarized by a mean and 95% confidence interval. Its stated timeframe is 8 hours. The definition relates the BIS index to the point at which 50% of subjects are considered unconscious according to MOAA/S scores of 0-2. No outcome analysis is listed in the registry record, and the endpoint estimate is not reported there.

These design details set limits on interpretation. The study can be described as collecting monitor data in a clinical setting, but its single-group structure does not by itself establish that differences between age groups are caused by age or by the monitor. The registry record does not report detailed eligibility criteria, the planned approach to selecting participants, or a statistical analysis plan. Those design details should not be inferred from the study title or its stated objective.

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

Reasons for not completing this period:

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: 15 subjects excluded from final analysis due to disqualification of BIS data

6. Primary Endpoint

The registry lists the primary outcome as BIS50, measured over 8 hours.

BIS50 is the primary endpoint. It uses the Bispectral Index, a scale from 0-100, where 0 represents no brain activity and 100 represents fully conscious, and identifies the value at which 50% of subjects are anesthetized at a level considered unconscious by the stated MOAA/S classification of 0-2. The registry describes the endpoint as a mean with a 95% confidence interval and gives an 8 hours timeframe.

The endpoint is intended to connect a monitor-derived index with a clinical assessment of consciousness. That connection is relevant to the study’s aim of examining age-related EEG signals and consciousness during anesthesia. A summary such as BIS50 can describe the index value associated with the stated threshold in the study population; it does not mean that every participant has the same BIS value at that threshold. Individual readings may vary, and a population mean does not convey the full spread of participant-level values.

A confidence interval communicates uncertainty around an estimated population quantity. A narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates less precision. The registry record does not report the BIS50 estimate or its confidence interval, so neither the estimated value nor its precision can be assessed from this record. The endpoint definition also does not, on its own, establish the accuracy of the BIS system or show whether the algorithm changed clinical decisions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists a continuous primary endpoint summarized by a mean and a 95% confidence interval. Those choices describe a statistical summary, but they do not reveal the full analysis method. The record does not report the calculation procedure for BIS50, assumptions used to estimate it, handling of repeated monitor readings, or the statistical model, if any. Such details are not reported in the registry record and should not be inferred from the endpoint name.

What does the mean describe?

As a general statistical concept, a mean is an average that summarizes a set of measurements. It can be useful when a study seeks a central value, but it does not describe every individual measurement or the amount of variation between participants. A mean may also be influenced by unusually high or low values. For BIS50, the registry states that the mean is the summary parameter, but does not report the observed estimate or other distributional summaries. Readers therefore cannot assess the observed spread or whether the mean represents the participant-level data well.

What does a confidence interval communicate?

As a general explanation, a confidence interval expresses uncertainty in an estimate under the assumptions of the method used to construct it. It is not a range intended to contain a fixed proportion of individual participant measurements. A confidence interval’s width reflects both the information in the data and the analysis method. The registry specifies a 95% confidence interval for BIS50, but does not report its limits. Without those limits, there is no basis to describe the precision of the primary estimate.

Why does the endpoint definition matter?

BIS50 is tied to a threshold defined using MOAA/S scores of 0-2 and to the point where 50% of subjects are classified as anesthetized at that level. This makes the endpoint dependent on how the monitor index and the consciousness classification are linked in the observed data. The endpoint definition does not explain how assessments were timed relative to BIS readings, how repeated readings were handled, or how the point associated with 50% was estimated. Those operational and analytical details are not reported in the registry record.

What can be learned from a single-group design?

As a general statistical principle, a single-group study can describe observations collected in its study setting, but it does not offer the same protection against confounding as a randomized comparison. Age is not assigned at random, and the registry record does not describe a randomized age comparison. Differences between age categories, if analyzed, could reflect other differences between participants or their clinical circumstances. The record does not report an age-stratified primary analysis, covariate adjustment, or a strategy for addressing confounding. The listed age categories in the safety record should not be treated as evidence of a primary-outcome comparison.

How should planning calculations be understood?

As a general distinction, planning calculations describe hypothetical study sizes under specified assumptions; they are not observed outcomes and are not evidence that a study had a particular probability of detecting an effect. The registry record states assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as stated fractions of an observed effect. It also specifies that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations use total events. These are planning assumptions, not a description of this study’s single-group design. The registry record does not report the study’s own sample-size justification, and no primary observed effect is reported in the registry record. Therefore those assumptions cannot be used to infer the study’s achieved precision or observed power.

Why does over-dispersion matter in general?

As a general statistical concept, over-dispersion occurs when observed variability is greater than the model expects. If a model assumes less variability than is present, standard errors and confidence intervals can be too small, making estimates appear more precise than the data warrant. The registry record does not identify a count-data model or report an over-dispersion assessment for this continuous endpoint. This concept is therefore relevant only as general statistical background, not as a reported feature of the analysis.

What analysis details remain unknown?

The registry record lists no analyses and does not report an analysis population, missing-data approach, treatment of repeated measurements, adjustment for covariates, or handling of protocol deviations. It also does not report interim analyses or a statistical analysis plan. These omissions limit reproducibility: readers cannot determine exactly how the endpoint would be calculated from participant-level observations or how uncertainty was quantified. The endpoint’s stated summary and timeframe are not substitutes for a complete statistical methods description.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analyses. It does not report a multiplicity plan, such as how statistical error would be controlled if multiple hypotheses, outcomes, or subgroup comparisons were evaluated. The presence of one listed primary measure does not establish that no additional analyses were performed; the record simply does not describe them. Any multiplicity procedures are not reported in the registry record.

Missing-data methods are also not reported in the registry record. There is no description of how missing BIS readings, incomplete consciousness assessments, withdrawals, or other unavailable measurements were handled. The record does not specify whether participants had to contribute a minimum amount of monitoring data to enter the primary analysis, or how any incomplete observation period would affect the endpoint. These omissions matter because the primary outcome depends on relating monitor values to a consciousness classification over the stated timeframe.

The analysis population is not reported in the registry record. Enrollment is recorded as 90, but the record does not state how many participants contributed to the primary outcome or define which enrolled participants would be included. The safety record has age-specific counts, but it does not establish the primary analysis denominator. Readers should not assume that enrollment and the analysis population are identical.

The registry record does not report prespecified subgroup analyses by age, adjustment methods, interim analyses, or a statistical analysis plan. It is therefore not possible to tell whether analyses were planned before data collection, how age was to be modeled, or whether any comparisons were exploratory. These are unknowns, rather than evidence that a particular method was or was not used.

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 adverse-event record lists two age categories. For Age 18-64, 39 participants are listed as at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. For Age 65+, 33 participants are listed as at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. No top serious adverse-event terms are listed.

These entries describe the counts recorded in the registry safety summary. A zero count means that no event of that listed type is recorded for the group in this registry entry; it does not establish that the event is impossible or that monitoring would never identify an event in other circumstances. The record does not report event definitions, ascertainment procedures, follow-up duration for safety, or whether all enrolled participants were included in these denominators.

The age-specific safety entries are not a randomized comparison. The registry record also does not report a causal safety analysis or estimates comparing risks between groups. These counts should therefore be read descriptively, without inferring that age or the BIS system caused or prevented an event. The relationship between the safety denominators and enrollment is not reported in the registry record.

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

The registry record documents a study designed to collect BIS measurements during standard-of-care elective surgery under general anesthesia. It identifies BIS50 as the primary endpoint and gives a clinical definition based on MOAA/S scores of 0-2. Those details explain what the study set out to measure. They do not reveal the observed endpoint value or the degree of uncertainty around it, because the primary result is not reported in the registry record.

The study title and stated purpose place age and the BIS algorithm at the center of the research question. But the record does not report an age-specific primary outcome, an age comparison, or evidence of algorithm performance. The listed age groups in the safety summary do not answer whether BIS50 varies with age. Nor can the objective of improving an algorithm be treated as evidence that an improvement occurred.

The primary endpoint is a population summary linked to a classification of unconsciousness. It is not an individual diagnostic guarantee. Even if a BIS50 estimate were reported, it would need to be interpreted alongside its confidence interval, the distribution of participant readings, the timing and quality of assessments, and the analysis methods. Those outcome details are absent from the registry record.

The completed status indicates the study is recorded as completed, but it does not supply the missing primary outcome result. The safety record reports zero recorded serious adverse events, other adverse events, and deaths in each listed age category, but does not provide enough detail to make broader safety claims. The appropriate conclusion from this record is limited: the study’s design and endpoint are described, while the primary findings and key analysis details are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically interesting because it links an instrument-derived signal to a clinical classification of consciousness, while focusing on whether age matters for the interpretation of those signals. Such a question involves more than reporting an average monitor value. It requires defining the clinical reference classification, specifying how readings and assessments are paired, and estimating uncertainty in the relationship between them. The registry identifies BIS50 and its MOAA/S-based definition, making the intended measurement target clear at a broad level.

The single-group design also highlights a distinction between collecting informative data and making comparative claims. Measurements gathered during routine elective surgery can describe the setting in which the monitor was used, but age-related differences would require an analysis that addresses how age is represented and what other factors may vary across participants. The registry record does not report such an analysis, so the scientific objective and the available result must be kept separate.

For biostatisticians and clinical researchers, the record illustrates why an endpoint definition is only part of an interpretable result. The estimate, uncertainty interval, analysis population, missing-data handling, and methods for repeated observations are all important to evaluating what the data support. Here, the endpoint definition and selected design characteristics are reported, but the primary result and detailed analysis methods are not reported in the registry record.

The safety counts likewise demonstrate the importance of describing denominators and ascertainment. Recorded zero events are informative as registry entries, but their meaning depends on who was observed, how events were captured, and for how long. Those details are not reported in the registry record. The statistical significance of the study’s topic should therefore not be confused with evidence of a particular result.

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 most direct limitation for interpretation is that the primary BIS50 result and its 95% confidence interval are not reported in the registry record. The record lists no analyses. As a result, readers cannot assess the estimate, its precision, the distribution of measurements, or whether the stated primary question was answered. There is also no reported age-stratified analysis of BIS50, despite age being central to the study title and objective.

The design is recorded as single-group, without allocation to a comparison condition and without masking. It is described as non-invasive data collection during standard-of-care elective surgery under general anesthesia. This supports a descriptive reading of the setting, but it does not provide a randomized control comparison. The registry record does not report whether or how the analysis would account for differences among participants or clinical circumstances.

Several details needed to assess the endpoint are not reported in the registry record: the operational timing of MOAA/S assessments relative to BIS values, handling of repeated readings, the estimator used for BIS50, the analysis population, and the approach to missing measurements. Detailed eligibility criteria and the representativeness of enrolled participants are also not reported. Without these details, the generalizability of any result cannot be evaluated from the registry entry.

The safety summary gives age-specific denominators and zero recorded events, but the record does not explain how safety events were defined or collected, the relevant observation period, or how the listed denominators relate to total enrollment. The registry record also does not report the study’s sample-size justification, statistical analysis plan, or interim analyses. These absences should be treated as limits of what the registry record reports, rather than evidence about what investigators may have done outside the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Influence of Age on EEG Signals and Consciousness During Anesthesia — NCT04765046.
• Registry record last updated 2024-07-03; status last verified 2024-06.
• Results first posted 2024-07-03.
• 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

NCT04765046 is recorded as a completed prospective, multicenter study of BIS monitoring during standard-of-care elective surgery under general anesthesia. Enrollment is recorded as 90. The listed primary endpoint is BIS50, a continuous mean with a 95% confidence interval, defined in relation to a MOAA/S unconsciousness classification of 0-2 and an 8 hours timeframe.

The registry describes a single-group, non-invasive data-collection design and states an aim of improving the current BIS algorithm in the elderly adult population. The primary BIS50 result, its confidence interval, and any primary outcome analysis are not reported in the registry record. The safety summary lists Age 18-64 and Age 65+ groups with zero recorded serious adverse events, other adverse events, and deaths in each. Detailed analysis, missing-data, and safety-ascertainment methods are not reported in the registry record.