Near Infrared Spectroscopy Cortical Response to Noxious and Auditory Stimuli in Subjects Under General Anesthesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Near Infrared Spectroscopy Cortical Response to Noxious and Auditory Stimuli in Subjects Under General Anesthesia (NCT02703090), a randomized na study. The primary outcome is Changes in Cortical Oxyhemoglobin Concentrations to Ablation.

2. Clinical Question

The study title also refers to auditory stimuli, and its brief summary describes measuring cortical responses to noxious stimulation under general anesthesia. The listed primary outcome, however, specifically concerns changes in cortical oxyhemoglobin concentrations to ablation. The registry record does not report a numerical answer to the primary question, so the direction and size of any group differences cannot be described.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group study. It lists the phase as NA and the status as completed. Enrollment is recorded as 44. The study start is listed as 2016-10, and primary completion as 2020-03-10. Boston Children's Hospital is identified as the sponsor.

Three arms are described: placebo, drug lower dose, and drug higher dose. The placebo arm received a normal saline infusion; both drug arms received remifentanil infusion. Specific remifentanil doses, the method used to generate the random allocation, and the people or roles included in the masking are not reported in the registry record. The terms randomized and triple-masked identify design features, but they do not establish details of how those features were implemented.

The primary outcome is a continuous measure: changes in peak oxyhemoglobin concentration, expressed in μM, in response to ablation. The recorded measurement window extends from 5 seconds before the start of an ablation event through the 20 seconds following its start. The outcome description frames the comparison as placebo versus the remifentanil groups. The registry record does not specify a numerical contrast, a model, or how the two remifentanil arms were handled in a primary statistical comparison.

The listed primary outcome population excludes subjects with inadequate fNIRS signals and subjects receiving cyroablation. The record gives n=7 for inadequate signals and n=2 for cyroablation, but does not report whether these exclusions overlap or provide further participant-flow details. The record lists three outcome measures and zero analyses. It does not report a protocol-based sample-size justification or additional design details that would clarify how enrollment was planned.

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: 44 participants were enrolled in the study. 41 participants completed the study. 3 participants were withdrawn from the study prior to any interventions. 32 participants data were analyzed (of the 41 completing the study, 7 participants were excluded due to poor fNIRS signal quality, and 2 participants were excluded because they received only cryoablations).

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled subjects with the exclusion of those with inadequate fNIRS signals (n=7) and those receiving cyroablation (n=2).

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 Changes in Cortical Oxyhemoglobin Concentrations to Ablation, measured over 5 seconds before the start of an ablation event and the 20 seconds following the start of ablation.

The primary endpoint is the change in peak oxyhemoglobin concentration (PeakHbO) in response to ablation, measured in μM. The registry describes the measure as a mean with standard error and defines the observation window as 5 seconds before the ablation event begins and the 20 seconds following its start. The population for this outcome excludes those with inadequate fNIRS signals and those receiving cyroablation.

The stated study aim is to use near-infrared spectroscopy to measure changes in brain blood flow in bilateral somatosensory and prefrontal cortices during noxious stimulation under general anesthesia. The primary endpoint operationalizes the ablation-related cortical response through a peak oxyhemoglobin concentration measure. It is therefore the named outcome for assessing the question about differences between placebo and remifentanil groups. It should not be read as a direct report of all cortical activity or as a clinical outcome beyond the measured concentration change.

In general, a continuous endpoint preserves information about the magnitude of a measurement rather than reducing it to event counts. The mean describes the central value of observations, while the standard error describes uncertainty in an estimated mean. The registry record contains no numerical group means, standard errors, or contrast for this endpoint, so its magnitude and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome type is continuous, and the registry specifies a mean with standard error. In general, a mean summarizes the center of a set of numerical observations. A standard error describes the sampling uncertainty associated with an estimated mean under a statistical model; it is not the same as the spread of individual measurements. A standard deviation describes variation among measurements, whereas a standard error concerns uncertainty in an estimate. The registry record does not provide the numerical means or standard errors needed to characterize this endpoint.

What would a group contrast represent?

A contrast is a defined comparison between groups, such as a difference between two group means. Its interpretation depends on which arms are included and how the comparison is specified. Here, the outcome description names placebo versus the remifentanil groups, and the arm descriptions distinguish lower-dose and higher-dose remifentanil. The registry record does not report the exact primary contrast or analysis model. It would be inappropriate to assume that the two remifentanil arms were pooled or analyzed separately.

In general, an estimate of a contrast is more informative when accompanied by an uncertainty interval. A confidence interval communicates the range of values compatible with the observed data and the assumptions of the analysis. It helps readers judge precision and the range of effects that remain plausible under that analysis. A p-value, if reported, addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the size or importance of an effect. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.

Why does the measurement window matter?

The endpoint is defined around an ablation event: 5 seconds before its start and the 20 seconds following the start. A time window defines which measurements contribute to an outcome, and the choice of summary within that window can affect what the estimate represents. The registry calls the measure peak oxyhemoglobin concentration, but does not report the detailed processing steps used to derive the peak, the timing of peak selection, or the method for handling repeated measurements. These details are not reported in the registry record and should not be inferred.

In general, measurements taken over time from the same subject may be statistically related. An analysis that uses multiple measurements must account for the way observations are grouped or correlated if it treats them jointly. The registry record does not report whether the primary analysis used individual time points, a peak summary, or a model for repeated measurements beyond naming the peak measure and timeframe.

How should randomization and masking be read?

The recorded design is randomized, triple-masked, and parallel. In general, randomization assigns participants to groups through a chance-based process and aims to make group comparisons less vulnerable to systematic differences at baseline. Masking can reduce the influence of group knowledge on study conduct or assessment. These design labels do not reveal how allocation was generated, how masking was maintained, or which roles were masked; those details are not reported in the registry record.

A parallel-group design means the record describes separate groups assigned to the listed arms rather than a sequence of treatments for every subject. The registry identifies placebo, drug lower dose, and drug higher dose arms. The interventions are normal saline and remifentanil, but specific drug doses and the timing or duration of infusions are not reported in the registry record.

What does the record say about statistical planning?

The registry lists zero analyses and does not report a statistical analysis plan, a sample-size justification, a planned model, or interim analyses. Those omissions do not establish what was or was not done outside the registry entry. They mean the posted record cannot be used to verify a prespecified test, adjustment strategy, or analytic decision. In general, prespecification helps readers distinguish planned analyses from choices made after results are known.

Sample-size planning illustrations are not observed power and are not results from the trial. A planning calculation generally depends on assumptions about the effect to detect, variability, significance level, allocation, and statistical method. The registry record does not report the trial's own sample-size justification or the assumptions that would permit one to interpret such planning as the study's design rationale. No new effect estimate or planning value can be derived from the information recorded for the primary outcome.

Finally, the registry says the primary outcome was not reduced to one comparison because it has several categories or time points. This limits direct interpretation of the primary result as a single contrast in the available record. In general, multiple outcomes or comparisons raise multiplicity questions: when many tests are considered, the chance of at least one apparently notable result can increase. Whether and how multiplicity was addressed is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and zero analyses. It does not report a complete statistical analysis plan, a primary comparison method, or any adjustment for testing multiple outcomes or contrasts. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The exact categories or time points used in that decision are not described beyond the endpoint timeframe recorded for ablation.

In general, multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. Without an appropriate plan, interpreting isolated results can overstate the evidence because the number of opportunities to find a seemingly notable result matters. This is a general concern, not a claim that the study used a particular number of tests or that any adjustment was required. The registry record does not report whether multiplicity was addressed.

The stated outcome population excludes subjects with inadequate fNIRS signals and those receiving cyroablation. The record identifies n=7 and n=2 for these respective exclusions. It does not report whether the categories overlap, how many subjects contributed usable endpoint data, whether other measurements were missing, or how any missing measurements were handled. It also does not state whether the analysis followed an intention-to-treat, per-protocol, or other population definition.

These missing details matter because the target population and handling of incomplete data shape the meaning of an estimate. In general, excluding observations can affect both the composition of the analyzed group and the precision of results. No assumptions about the causes or consequences of the listed exclusions can be made from the registry record. The record's endpoint-population description should therefore be distinguished from an undocumented analysis population.

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 registry reports serious adverse event figures separately for placebo, drug lower dose, and drug higher dose. For serious events, the listed numbers at risk are 14 for placebo, 14 for drug lower dose, and 13 for drug higher dose; the corresponding numbers affected are 0, 0, and 0. The registry also lists deaths as 0 in each of these groups.

These counts describe what is recorded for the listed groups. They do not establish that no other adverse events occurred: the figures concern serious adverse events and deaths, and the record does not provide top serious-event terms. Nor do zero recorded serious events establish that the interventions are free of risk. The listed numbers at risk are group-specific and should not be interpreted as the primary endpoint population, whose exclusions are described separately.

In general, safety counts are most informative when the observation period, event definitions, and completeness of reporting are clear. The registry record does not give further detail about event collection, follow-up duration, or the criteria used to classify events as serious. These figures should be read as the recorded counts, not as proof of absence of harm or as a comparison demonstrating a safety difference.

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

The registry record establishes that this was a completed, randomized, triple-masked, parallel-group study of near-infrared spectroscopy under general anesthesia, with placebo and two remifentanil arms. It identifies the primary outcome as change in peak oxyhemoglobin concentration in response to ablation and defines a measurement window around the start of the event. It also describes exclusions from the primary outcome population.

What the registry record does not establish is the direction, size, or precision of the primary group comparison. Numerical endpoint estimates and a statistical analysis are not reported. Therefore, the record does not show whether peak oxyhemoglobin concentrations differed between placebo and remifentanil groups, whether a difference was statistically distinguishable from no difference, or how uncertain any estimate would be. Lack of a reported estimate should not be mistaken for a result showing no difference.

The outcome is a measured cortical oxyhemoglobin response. It is not, by itself, a report of patient benefit, a clinical decision outcome, or a general conclusion about anesthesia or pain. The registry's brief summary states an aim of measuring changes in brain blood flow, while the primary endpoint is specified as oxyhemoglobin concentration. The available record does not provide numerical results that would support further interpretation of the physiological response.

The safety figures record zero serious adverse events and zero deaths in each listed group, with group-specific numbers at risk. Those counts are limited to what is registered and do not prove absence of other harms or establish a comparative safety conclusion. Taken together, the record permits careful description of design, endpoint, exclusions, and recorded safety counts, but not an efficacy conclusion or a quantitative interpretation of the primary result.

13. Why This Trial Matters Statistically

This trial raises statistical questions that are especially visible when a physiological measurement is taken around a defined stimulus. A continuous endpoint such as peak oxyhemoglobin concentration needs a clear definition, a stated comparison, and an account of uncertainty before readers can assess the size and precision of a group difference. The registry record identifies the measure and timeframe, but does not report the numerical comparison or analysis.

The design also includes three arms, with two remifentanil groups and a saline placebo group. That structure makes the exact contrast important: a comparison of each drug arm with placebo answers a different question from a pooled comparison of both drug arms with placebo. The registry describes the primary comparison broadly as placebo versus remifentanil groups but does not specify how that contrast was analyzed. This is a reason to distinguish arm descriptions from a defined statistical estimand.

The outcome population excludes subjects with inadequate fNIRS signals and those receiving cyroablation. Such exclusions make it important to define the analysis population and explain how unavailable measurements are handled. The registry gives the exclusion counts but does not report overlap, additional missing-data details, or the analysis population used. These gaps limit reproducibility and the scope of interpretation.

Finally, the record says the primary outcome had several categories or time points and was not reduced to one comparison, while listing zero analyses. That combination underscores why reporting a prespecified outcome definition, analysis strategy, multiplicity approach, and numerical estimates matters. Without those elements, readers can identify the intended measurement and design but cannot evaluate the primary statistical evidence. The statistical importance lies in separating a clearly stated research question from an unreported 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 main limitation for interpreting this trial from its registry record is that numerical results for the primary endpoint are not reported. The record lists zero analyses, so there is no posted group estimate, contrast, uncertainty interval, or test result to evaluate. The planned or completed statistical method is not reported in the registry record.

The outcome description identifies placebo versus remifentanil groups, while the design has separate lower-dose and higher-dose remifentanil arms. The registry does not define the primary contrast or report how those arms were incorporated. Specific remifentanil doses are also not reported, so the lower-dose and higher-dose labels cannot be linked to numerical doses from the record.

The stated primary outcome population excludes subjects with inadequate fNIRS signals and those receiving cyroablation. Although the record gives n=7 and n=2 for these exclusions, it does not say whether they overlap or report further details about missing endpoint measurements. It does not identify the analysis population or describe missing-data handling.

Other design and analysis details are not reported in the registry record, including how random allocation was generated, which roles were masked, how the peak measure was derived, and what statistical model was planned. The record also does not report a sample-size justification or how multiplicity was addressed. These omissions restrict assessment of reproducibility, precision, and the relationship between the registered question and any analysis.

The safety figures are limited to the recorded serious-event counts and deaths. The record does not provide further event terms or details about ascertainment and follow-up. These limitations do not imply that unreported procedures or events did not occur; they define what can be assessed from the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Near Infrared Spectroscopy Cortical Response to Noxious and Auditory Stimuli in Subjects Under General Anesthesia — NCT02703090.
• Registry record last updated 2025-12-15; status last verified 2025-12.
• Results first posted 2025-12-15.
• 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

NCT02703090 is recorded as a completed, randomized, triple-masked, parallel-group study sponsored by Boston Children's Hospital. Enrollment is listed as 44; the phase is NA. The start is recorded as 2016-10 and primary completion as 2020-03-10.

The study compares normal saline placebo with lower-dose and higher-dose remifentanil arms during general anesthesia. Its primary outcome is the change in peak oxyhemoglobin concentration to ablation, measured in μM over a window from 5 seconds before the event to the 20 seconds following its start. The stated outcome population excludes subjects with inadequate fNIRS signals and those receiving cyroablation.

The registry record reports zero analyses and no numerical primary outcome results. It lists zero serious adverse events and zero deaths in each group, with group-specific numbers at risk. The numerical effect, its precision, and the statistical method for the primary comparison are not reported in the registry record.