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 Improving Information Extraction From EEG on Cerebral Anesthetic Drug Effects (NCT02043938), a na na study. The primary outcome is Patient State Index (PSI) Comparison, Baseline and Emax.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02043938 |
| Phase | NA |
| Condition | Anesthesia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 46 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Masimo Corporation |
| Results posted | Yes |
2. Clinical Question
Population
The population described for the primary outcome is healthy volunteers. The registry states that all 36 participants experienced each of the four interventions. The broader study enrollment is listed as 46, but the record does not explain how that enrollment relates to the 36 participants described for the primary outcome.
Intervention
The study used four anesthesia regimens: propofol only, sevoflurane only, propofol with remifentanil, and sevoflurane with remifentanil. SedLine EEG sensors were placed on participants’ foreheads during the sessions. The study collected raw EEG waves during standardized drug titration.
Comparator
The regimens offer within-participant contrasts across different drug combinations. However, the record does not establish a parallel control group or report a randomized comparison between regimens. The allocation field is listed as not reported, and the registry cautions that the arms are not a like-for-like control comparison.
Primary question
The primary outcome concerns Patient State Index comparisons at baseline and maximum drug effect. The study description also frames the comparison around how PSI-1 and PSI-2 correlate with measured propofol and sevoflurane concentrations, with or without remifentanil, using estimated pharmacodynamic model parameters. Numerical results for those comparisons are not reported in the registry record.
In statistical terms, the study asks whether processed EEG measures capture changes associated with anesthetic exposure across the specified regimens. It also considers whether a newer PSI algorithm performs differently from PSI-1, particularly in low-power EEG. That is a measurement and pharmacodynamic question, not a test of clinical outcomes. The record does not report estimates that would show the size or precision of any difference between algorithms or regimens.
3. Trial Design
This completed interventional study enrolled healthy volunteers and collected EEG data during anesthesia. The registry lists the start date as 2013-12-16 and the primary completion date as 2015-06-04. The stated study focus is the cerebral effects of propofol, sevoflurane, and remifentanil as measured by spontaneous EEG. SedLine EEG sensors were the listed device intervention.
The primary-outcome description identifies 36 participants who each experienced all four regimens: propofol only, sevoflurane only, propofol with remifentanil, and sevoflurane with remifentanil. This is a repeated-exposure structure: measurements from the same participant across regimens are related and should not automatically be treated as independent observations. The record does not describe the order of sessions, the method used to assign that order, or any washout procedures.
There is a difference between the listed enrollment of 46 and the 36 participants described for the primary outcome. The registry record does not explain this difference or provide a participant-flow account. Its brief summary calls the study randomized, but allocation is listed as not reported, and the record cautions that this is not a randomized comparison. The sequence generation, allocation procedures, and any role of masking are therefore not established by the registry fields. Masking is listed as none.
The record marks the study completed and lists no analysis records. It identifies four outcome measures, but numerical estimates for the primary endpoint are not present in the available description. Details of the protocol, analytic plan, and the rationale for the enrollment target 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
| Stage | Healthy Volunteers |
|---|---|
| STARTED | 46 |
| COMPLETED | 36 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Healthy Volunteers |
|---|---|
| Withdrawal by Subject | 7 |
| Unable to place EEG sensors on patient | 1 |
| No show by subject | 1 |
| Investigator decision | 1 |
Analysis population for the primary outcome, as defined in the registry: All 36 participants experienced all four interventions: Propofol only (P), Sevoflurane only (S), Propofol with Remifentanil (PR), and Sevoflurane with Remifentanil (SR).
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 | Healthy Volunteers |
|---|---|---|
| Participants analysed | 36 | |
| Age, Continuous | years | 43.3 (20 to 70) |
| Sex: Female, Male: Female | Participants | 20 |
| Sex: Female, Male: Male | Participants | 16 |
| Region of Enrollment: Netherlands | Participants | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Patient State Index (PSI) Comparison, Baseline and Emax, measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | index |
| Endpoint classification | Continuous Endpoint |
The primary outcome is titled Patient State Index comparison at baseline and Emax. PSI is a processed EEG parameter intended to quantify the level of EEG inhibition. The record describes PSI as unitless, with a scale from 100, representing an awake state, to 0, representing no detectable electrical brain activity. PSI-1 is the existing measure described in the record, while PSI-2 is a newer algorithm intended to improve performance in low-power EEG.
Baseline refers to PSI-2 measurements when no drug is present. Emax refers to PSI in the presence of the maximum drug effect. The endpoint description also discusses comparing PSI-1 and PSI-2 in their correlation with measured propofol and sevoflurane concentrations, including regimens with remifentanil. The model parameters include C50, the drug concentration associated with 50% of the maximum drug effect; the concentration units differ by drug, as stated in the registry description.
Using EEG measures alongside measured drug concentrations can characterize how a signal changes across anesthetic exposure. Such measures are useful for studying pharmacodynamic relationships, but they are not themselves direct evidence about patient-centered clinical outcomes. The registry lists the endpoint as a mean with standard error, but its numerical estimates and uncertainty intervals are not reported in the registry record. Consequently, the direction, magnitude, and precision of the PSI comparisons cannot be assessed from the recorded results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry gives a clear description of the scientific target: compare EEG-derived measures across anesthetic exposures and assess how PSI measures relate to measured drug concentrations. It does not, however, provide the numerical primary-outcome results. There are no reported group means, standard errors, effect estimates, confidence intervals, or test results in the record available for this analysis. The endpoint title alone cannot establish whether PSI-1 or PSI-2 had a stronger relationship with drug concentration, or whether any observed contrast was large or precise.
The listed outcome is a mean with standard error. A mean describes the average value in the analyzed observations, while a standard error describes the precision of an estimated mean under the analysis used. It does not describe the spread of individual EEG values in the same way as a standard deviation. Without the actual means and standard errors, neither the location of the estimated PSI values nor the uncertainty around them can be interpreted.
The primary-outcome description refers to baseline and Emax, as well as estimated pharmacodynamic parameters. These are distinct features of the analysis: baseline characterizes measurements in the absence of drug, while Emax describes the PSI at maximum drug effect. The record also describes C50 as a concentration parameter. No estimates of baseline, Emax, C50, or other model parameters are reported, so the concentration-response pattern cannot be reconstructed from the registry entry.
The study’s repeated-exposure structure matters when interpreting any comparison. Since the same 36 participants experienced all four regimens, measurements across regimens are linked within people. An analysis that accounts for this relationship can differ in its uncertainty from an analysis that treats all regimen observations as independent. The statistical model used for the posted endpoint is not reported in the registry record, so its treatment of within-participant correlation cannot be evaluated.
The registry lists no analysis records. It also does not provide a numerical estimate that can be independently checked or recalculated from summary statistics. Therefore, there is no basis in this record for judging statistical significance, estimating the size of an effect, or assessing how sensitive a result might be to modeling choices. The absence of numerical results in the registry does not establish that the study found no association or no difference; it means that the registry record does not report the estimates needed to assess those questions.
9. Statistical Methods Explained
The following statistical explanations are general. The registry record does not describe the methods used to produce the primary outcome estimates, so these concepts explain how such results are commonly interpreted rather than asserting which procedures this study used.
What does a mean and standard error describe?
A mean summarizes the central value of a continuous measurement across observations included in an analysis. The standard error describes the statistical precision of an estimated mean, given the observations and model. It is not interchangeable with the standard deviation: the standard deviation describes variability among observations, while the standard error concerns uncertainty in an estimated quantity. A smaller standard error generally indicates a more precise estimate under the assumptions of the analysis, but it does not show whether the estimate is clinically important or whether the model is appropriate.
The registry labels the primary outcome as a mean with standard error, but it does not report the means or standard errors. Readers therefore cannot assess the observed values, the degree of uncertainty, or whether the precision differs across regimens. No confidence interval for the primary endpoint is reported in the registry record.
What does a confidence interval add?
In general, a confidence interval expresses uncertainty around an estimated quantity using a range of values compatible with the data and the assumptions of the method. Its width reflects precision: a narrower interval indicates more precise estimation than a wider interval, all else being equal. The interval does not give the probability that a fixed true value lies within the particular calculated interval. Since the registry does not report confidence intervals or the underlying numerical estimates for this endpoint, the precision of any PSI contrast cannot be assessed from the record.
Why does the repeated-measures structure matter?
When the same participant contributes observations under multiple conditions, those observations tend to be related because they share characteristics of that participant. General methods for repeated measures account for this dependence, rather than assuming that each observation is unrelated to every other observation. Ignoring the dependence can misstate uncertainty. The record indicates that all 36 participants experienced all four interventions, but it does not identify the model used, the covariance assumptions, or how incomplete measurements were handled.
Within-participant comparisons can control for stable differences between participants, but they do not remove all sources of bias or uncertainty. Session order, changes over time, measurement error, and other time-varying factors can still matter. The registry record does not report enough session-level detail to assess these issues.
How should the pharmacodynamic terms be read?
In general, a pharmacodynamic model describes how a measured response changes with drug exposure. Emax represents a modeled maximum effect, while C50 represents the concentration associated with half of that maximum effect, as defined in the registry description. These are model-based parameters, not direct summaries of every individual measurement. Their interpretation depends on the chosen model, the quality and range of concentration measurements, and the way repeated observations are handled. The registry does not report fitted parameter values, model equations, diagnostics, or uncertainty estimates.
PSI-1 and PSI-2 are processed EEG measures, and the study description frames their comparison in relation to measured drug concentrations. Correlation describes the strength and direction of an association between measured quantities. It does not by itself establish that one quantity causes another, and it does not necessarily describe agreement between two measurement methods. The record does not report the correlations or specify their calculation, so it is not possible to evaluate their magnitude or precision.
What does over-dispersion mean in general?
Over-dispersion occurs when observed variability is greater than a statistical model expects. It is most often discussed with count outcomes, but the broader lesson is that a model’s assumptions about variation should be checked. If variability is understated, uncertainty estimates can be too small and tests can appear more decisive than warranted. This endpoint is described as continuous, and the registry does not report a variance assessment or a model diagnostic. It would therefore be inappropriate to claim that over-dispersion occurred in this study.
What can a planning illustration say?
A sample-size calculation is a planning exercise: it estimates how many participants per arm might be needed under specified assumptions to detect a chosen effect with a chosen power. It is not an observed result and does not establish the power achieved by a completed study. The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also distinguishes planning for participants per arm from total events in time-to-event settings.
Those assumptions do not establish the study’s original design rationale. The record says the planning illustration is based on the observed effect and is not the trial’s own design. No numerical planning estimates are reported in the registry record here, and no sample-size justification, interim-analysis plan, or analysis plan is reported. A planning illustration should not be described as observed power or used to infer whether the study was adequately powered.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures but does not provide the complete outcome definitions or numerical results for them. It reports no analysis records. The primary outcome description includes several related features: PSI-1 and PSI-2, baseline and Emax, different anesthetic regimens, measured drug concentrations, and estimated pharmacodynamic parameters. This creates multiple possible statistical comparisons, but the registry record does not state which comparisons were prespecified as primary, how many were tested, or how multiplicity was handled.
Multiplicity matters because examining many outcomes or contrasts can increase the chance of obtaining a seemingly notable result by chance. General approaches can include prespecifying a primary contrast, adjusting inference across a defined family of tests, or presenting estimates with appropriate caution. The record does not report whether any such method was used. It would not be appropriate to assume either that adjustment occurred or that it was unnecessary.
Missing-data methods are also not reported. The outcome description says that all 36 participants experienced all four interventions, but that does not establish that every planned EEG measurement was available or included in every analysis. The registry lists enrollment as 46 and identifies 36 participants for the primary outcome, without explaining the relationship between those counts. Reasons for non-inclusion, missing session data, exclusions, and any imputation or sensitivity analyses are not reported in the registry record.
The analysis population is not fully specified beyond the primary-outcome description. The record does not state whether analyses included all available measurements, required complete measurements across regimens, or used another rule. These omissions limit assessment of potential selection effects and the reproducibility of the statistical results.
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 |
|---|---|---|---|
| Healthy Volunteers, Propofol (P) | 0 | 36 | 0.0% |
| Healthy Volunteers, Sevoflurane (S) | 0 | 36 | 0.0% |
| Healthy Volunteers, Propofol With Remifentanil (PR) | 0 | 36 | 0.0% |
| Healthy Volunteers, Sevoflurane With Remifentanil (SR) | 0 | 36 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Healthy Volunteers, Propofol (P) | 0 of 36 |
| Healthy Volunteers, Sevoflurane (S) | 0 of 36 |
| Healthy Volunteers, Propofol With Remifentanil (PR) | 0 of 36 |
| Healthy Volunteers, Sevoflurane With Remifentanil (SR) | 0 of 36 |
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 |
|---|---|
| Healthy Volunteers, Propofol (P) | 1 of 36 |
| Healthy Volunteers, Sevoflurane (S) | 2 of 36 |
| Healthy Volunteers, Propofol With Remifentanil (PR) | 1 of 36 |
| Healthy Volunteers, Sevoflurane With Remifentanil (SR) | 7 of 36 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Healthy Volunteers, Propofol (P) | Healthy Volunteers, Sevoflurane (S) | Healthy Volunteers, Propofol With Remifentanil (PR) | Healthy Volunteers, Sevoflurane With Remifentanil (SR) |
|---|---|---|---|---|---|
| Vomiting | General disorders | 0 of 36 | 2 of 36 | 0 of 36 | 2 of 36 |
| Urine tract infection | Renal and urinary disorders | 0 of 36 | 0 of 36 | 1 of 36 | 2 of 36 |
| Hypotension | Vascular disorders | 0 of 36 | 0 of 36 | 0 of 36 | 1 of 36 |
| Pain at arterial line site | Injury, poisoning and procedural complications | 0 of 36 | 0 of 36 | 0 of 36 | 1 of 36 |
| Temporary numb sensation in hand | General disorders | 1 of 36 | 0 of 36 | 0 of 36 | 0 of 36 |
| Short phase of nodale ECG rhythm | Cardiac disorders | 0 of 36 | 0 of 36 | 0 of 36 | 1 of 36 |
The adverse-event record lists four regimen-specific groups, each with 36 participants at risk. It reports 0 serious adverse events and 0 deaths for each regimen. These are registry counts for the recorded categories; they should not be interpreted as proof that the risk of serious harm is absent. The registry does not provide a comparative safety analysis or uncertainty estimates for these counts.
Other adverse events were recorded as 1 for propofol, 2 for sevoflurane, 1 for propofol with remifentanil, and 7 for sevoflurane with remifentanil. The registry does not provide detail in this record about the event terms, severity, timing, attribution, or whether the same participant could contribute events under more than one regimen. Because the primary description says the same 36 participants experienced all four interventions, the regimen-specific entries should not be added together or treated as independent groups.
The adverse-event counts describe what the registry recorded, not a randomized between-group safety comparison. The allocation field is not reported, and the study is not described as a like-for-like control comparison. The record does not report the duration of safety follow-up beyond the endpoint timeframe, or provide additional information needed to assess comparative safety. These figures are descriptive and should be read within those limits.
12. What the Result Does, and Does Not, Mean
The study is designed to examine EEG measurements during anesthetic exposure in healthy volunteers. Its primary endpoint concerns PSI at baseline and maximum drug effect, with the broader description focused on comparing PSI-1 and PSI-2 in relation to measured propofol and sevoflurane concentrations, including regimens with remifentanil. The registry thus frames a measurement and pharmacodynamic question.
The available record does not report the numerical primary-outcome results. It does not show the estimated PSI values, the difference between algorithms or regimens, the fitted concentration-response parameters, or the uncertainty around those quantities. Consequently, the record cannot establish the direction, magnitude, precision, or statistical significance of the primary comparisons. A missing result in the registry is not evidence that the effect was absent; it means that the result cannot be evaluated from the recorded information.
Even if an association between PSI and measured drug concentration were reported, that association would not by itself establish that the measure improves clinical outcomes or is suitable for every setting. PSI is a processed EEG parameter, and this study’s stated focus is on its behavior as an EEG measure during controlled anesthetic sessions in healthy volunteers. The registry does not report outcomes that would support conclusions about clinical benefit, patient management, or performance in other populations.
The within-participant exposure to all four regimens is relevant to interpretation because measurements are related within individuals. The registry does not specify the statistical model, session order, missing-data approach, or multiplicity strategy. These omissions prevent a full assessment of whether the analyses addressed dependence, selection, and the range of planned comparisons.
The safety record reports no serious adverse events or deaths in the listed regimen groups, and it records other adverse events. These descriptive counts do not constitute a comparative safety estimate. Taken together, the registry offers useful information about the study question, exposure structure, and planned endpoint, but does not provide the numerical findings required to judge what the primary analysis showed.
13. Why This Trial Matters Statistically
This study raises an important statistical measurement question: whether processed EEG indices track changes in anesthetic exposure, and whether PSI-2 behaves differently from PSI-1 in low-power EEG. Such questions are distinct from asking whether a treatment changes a clinical outcome. Separating measurement performance from clinical effectiveness helps readers understand what an endpoint can and cannot establish.
The design also highlights why repeated measurements need careful analysis. Each participant experienced all four regimens, so observations from the same person are connected. Recognizing this dependence is central to valid uncertainty estimates and fair comparisons. A within-participant design can be informative, but only if the analysis reflects its structure and if the session procedures and missing observations are clearly documented.
The pharmacodynamic framing is another statistical feature of interest. Baseline, Emax, and C50 describe different aspects of a modeled concentration-response relationship. Reporting these estimates with uncertainty, model details, and diagnostics would allow readers to assess whether the model is supported by the observed data and how precisely each parameter is estimated. The registry describes these quantities but does not report their values.
The record also illustrates the difference between a study description and a usable results record. It identifies the population, interventions, endpoint concepts, and adverse-event counts, while the numerical primary findings and analysis details are absent. Without estimates and uncertainty, readers cannot judge the strength or stability of the reported statistical evidence. Transparent reporting of the analysis population, missing-data handling, multiplicity decisions, and model specification would make the measurement question more reproducible and interpretable.
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 main limitation for statistical interpretation is that the registry record does not report numerical primary-outcome estimates. Means, standard errors, confidence intervals, test results, and pharmacodynamic parameter estimates are absent. This prevents direct evaluation of effect size, precision, and the relationship between PSI measures and drug concentrations.
The participant counts are not fully reconciled. Enrollment is listed as 46, while the primary-outcome description says that all 36 participants experienced all four interventions. The registry does not explain this difference, report participant flow, or identify reasons for non-inclusion in the primary outcome. It also does not report whether all sessions and measurements were complete.
Important design and analysis details are missing. Allocation is listed as not reported, although the brief summary calls the study randomized; the record also cautions that this is not a randomized comparison. The order of regimens and any procedures to address order effects are not described. The statistical model, treatment of within-participant dependence, model diagnostics, missing-data methods, and multiplicity procedures are not reported in the registry record.
The endpoint is a processed EEG measure, and the study description concerns healthy volunteers under the specified anesthesia sessions. The record does not provide results that establish performance in other populations or connect PSI differences to clinical outcomes. The adverse-event information is also limited to regimen-specific counts, without detailed event descriptions or a comparative analysis. These limitations mean the registry can describe the study’s aims and structure, but it cannot support a complete assessment of its statistical findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Improving Information Extraction From EEG on Cerebral Anesthetic Drug Effects — NCT02043938.
- Registry record last updated 2018-05-02; status last verified 2018-03.
- Results first posted 2018-05-02.
- 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
NCT02043938 is a completed interventional study of EEG measurements during propofol and sevoflurane anesthesia, with and without remifentanil, in healthy volunteers. The record lists enrollment of 46 and states that all 36 participants in the primary-outcome description experienced all four regimens. SedLine EEG sensors were used during the sessions.
The primary endpoint is a PSI comparison at baseline and Emax. The description discusses PSI-1 and PSI-2, measured drug concentrations, and pharmacodynamic parameters. Numerical primary-outcome results and analysis details are not reported in the registry record. Serious adverse events and deaths are recorded as 0 in each regimen group; other adverse-event counts are also listed. The allocation field is not reported, and the registry cautions that the regimens are not a like-for-like control comparison.