EEG Studies of Ketamine General Anesthesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EEG Studies of Ketamine General Anesthesia (NCT03553758), a na phase 2, phase 3 study. The primary outcome is Average Pain Intensity Pre- and Post-Ketamine Induction.

2. Clinical Question

3. Trial Design

This is a completed, single-group study listed as phase 2 and phase 3. The registry lists Massachusetts General Hospital as the sponsor, the condition as anesthesia, and ketamine as the drug intervention. The recorded enrollment is 16, while the arm description states that 15 subjects underwent ketamine general anesthesia. These are separate entries in the record; the reason for the difference is not reported.

Allocation is listed as not applicable, and masking is listed as none. There is no randomized comparison or like-for-like control arm. The principal design feature relevant to interpretation is that the primary outcome is measured at multiple times around ketamine induction within the study group. Such observations can describe the course of measured pain intensity over time, but without a control group they do not isolate the effect of ketamine from other influences that may change over the same period.

The registry lists a start date of 2018-11-01, a primary completion date of 2019-02-01, and a completed status. Its summary describes EEG measurement of brain electrical activity and assessment of pain responses. It does not report the detailed study setting, eligibility criteria, recruitment procedures, or how the EEG measurements were analyzed. A sample-size justification and the trial's own statistical analysis plan 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 1 patient did not complete assessments after recovery of responsiveness.

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: 1 patient was enrolled in the study, but did not complete any study activities.

6. Primary Endpoint

The registry lists the primary outcome as Average Pain Intensity Pre- and Post-Ketamine Induction, measured over Approximately 125 minutes.

The primary endpoint is average pain intensity before and after ketamine induction. The registry describes the PROMIS Pain Intensity 1a measure, used to assess pain delivered by a pre-calibrated pain cuff. Its scale runs from 0, meaning no pain, to 10, meaning worst imaginable pain. Measurements are described prior to induction and at 30, 60, 75, and 120 minutes after ketamine; the stated timeframe is approximately 125 minutes.

Pain intensity is a patient-reported experience, so repeated assessments can describe how reported pain changes across the study period. Reporting an average gives a summary of the measured scores, while a standard deviation describes variation among scores around that average. These are different features: the average concerns the central level of the scores, and the standard deviation concerns their spread.

The registry lists a mean and standard deviation as the outcome measure, but does not provide the numerical values. One patient did not complete assessments after recovery of responsiveness. The record does not clarify which individual timepoint values are available for that patient or provide a numerical analysis accounting for incomplete assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary measure as continuous and describes it using a mean and standard deviation. In general, a mean is an average across observed measurements. A standard deviation describes how dispersed those measurements are around the mean. A mean alone does not reveal whether the individual observations cluster closely or vary widely, so the two summaries answer different descriptive questions.

What do repeated measurements contribute?

The outcome is assessed before ketamine induction and at several specified times afterward. In general, measurements repeated on the same person can describe within-person change over time, as well as variation between people. The observations from the same person are related rather than independent. A statistical analysis of repeated measurements should account for that dependence if it estimates an overall time pattern or compares timepoints. The registry does not report whether such an analysis was conducted, which model was used, or whether comparisons between timepoints were planned.

A useful general distinction is between describing each timepoint and estimating change. Timepoint summaries describe the observed scores at each assessment. An estimate of change compares measurements across times, ideally making clear which observations contribute and how their relationship is handled. The registry provides the assessment schedule but no numerical summaries or change estimates. It is therefore not possible to describe the observed trajectory or its uncertainty from the registry record.

What does uncertainty mean?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. Its width reflects both the amount and variability of the information available and the method used to calculate it. An interval is not a guarantee that the true value lies within its limits. No confidence interval is reported for the primary outcome in the registry record, so its precision cannot be assessed from the posted information.

A p-value, in general, measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions apply. It does not measure the size or clinical importance of an effect. The registry lists 0 analyses and does not report a p-value for the primary outcome. There is no basis in the record for describing the primary result as statistically significant or not statistically significant.

Why does the design matter for analysis?

Because the study is single group and has no randomized control arm, the main comparison described by the endpoint is across time within the ketamine group. A within-group change is not equivalent to a randomized treatment contrast. General statistical adjustment cannot create the protection against confounding that random allocation to a comparison group can provide when that comparison is absent. The registry does not report an adjusted analysis or any other approach intended to address time-related influences.

The arm description and enrollment entry do not match, and the endpoint description notes incomplete assessments for one patient after recovery of responsiveness. In general, incomplete repeated measurements can affect both the amount of information and the interpretation of an average or change estimate. A complete-case analysis, an analysis using available measurements, and a model-based approach can rely on different assumptions. The registry does not report which approach was used or whether assumptions about missingness were assessed.

What do the planning assumptions represent?

The record describes sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect to detect is a stated fraction of the observed effect. In general, such calculations are planning exercises for a hypothetical design; they are not outcomes from the study and are not observed power. Their assumptions do not match the recorded single-group design. The numerical illustrations and the trial's own sample-size justification are not reported in the registry record.

Over-dispersion is a general concern when count data vary more than a statistical model expects. It is not a stated feature of this continuous pain endpoint, which is summarized as a mean and standard deviation. The registry does not report a distributional assessment or the model used for the pain scores, so no claim about model fit or distribution can be made.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is measured at multiple timepoints, and the registry also lists two secondary outcomes: average dissociation states score before and after ketamine induction, and the difference in mean clinician-administered dissociative states scale before and after midazolam administration. Considering multiple outcomes or multiple timepoint comparisons can increase the chance of finding at least one apparently unusual result by chance. In general, a prespecified analysis plan may identify a primary comparison or describe an adjustment for multiple testing. Neither a multiplicity strategy nor a detailed analysis plan is reported in the registry record.

The registry lists 3 outcome measures and 0 analyses. It does not provide numerical results for the primary or secondary outcomes, nor does it state which comparisons were performed or how they were prioritized. The record therefore does not support an assessment of multiplicity handling or a reconstruction of the reported analysis.

One patient did not complete assessments after recovery of responsiveness. The registry does not report which post-recovery measurements were unavailable, how missing values were handled, or whether the analysis included all available measurements or a defined subset. It also does not report a missing-data assumption or sensitivity analysis. Those details matter because methods for incomplete repeated outcomes can produce different estimates under different assumptions.

The registry does not define an intention-to-treat, per-protocol, or other analysis population. The discrepancy between recorded enrollment of 16 and an arm description of 15 subjects is not explained. It should not be resolved by assuming that either entry represents the analyzed 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 adverse-event record lists the Ketamine group with 15 at risk for serious adverse events and 0 affected. It also lists 15 at risk for other adverse events and 0 affected, with 0 deaths. These are the recorded counts and denominators; they do not describe the nature, timing, or duration of safety monitoring.

A count of 0 means that no events of the specified type are recorded in the listed group in this registry entry. It does not establish that an event could not occur, or that no events occurred outside the period or definitions used for reporting. The registry lists no top serious-event terms. The reason the adverse-event denominators are 15 while recorded enrollment is 16 is not reported in the registry record.

The safety entries do not provide a comparison group. They therefore cannot support a comparative estimate of event risk between ketamine and another treatment. They should be read as the posted event counts for the listed group, not as proof of an absence of risk or as a general safety conclusion.

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

The registry record describes a study intended to investigate ketamine's effects on brain activity and pain responses during general anesthesia. Its primary outcome is average pain intensity assessed before and at several times after induction. The posted information specifies the measure, scale, and assessment schedule, but does not report the numerical outcome values or a statistical analysis.

As a result, the record does not show how pain scores changed, how variable the scores were, or how precisely a change was estimated. It also does not report numerical results for the listed secondary outcomes. Without estimates and their uncertainty, the magnitude and pattern of the measured outcomes cannot be interpreted from this record.

The study's single-group design can describe observations within the ketamine group over time. It cannot, on its own, establish what would have happened over the same period in a control group or separate changes associated with induction from other time-related influences. This is a design limitation, not a conclusion about the direction or size of any measured change.

The listed safety counts are 0 serious adverse events, 0 other adverse events, and 0 deaths among the recorded denominators. These entries are limited to the registry's reported counts and do not show comparative risks or establish that risk is absent. The incomplete assessments and unexplained difference between the enrollment entry and arm description further limit interpretation of who contributed to each outcome.

13. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and a reported result are not the same thing. The registry specifies a continuous pain measure, its scale, and a sequence of assessment times. Those details explain what was intended to be measured, but without numerical estimates they do not reveal the observed pattern or its precision.

Repeated measurements can be valuable because they describe how observations evolve across time. They also create analysis questions: observations from one person are related, assessment completion may vary, and multiple timepoint comparisons can complicate interpretation. The registry does not report how these issues were addressed. Recognizing what is missing is part of evaluating the strength of the statistical evidence, rather than filling gaps with assumed methods.

The single-group structure is equally important. Before-and-after measurements can characterize change within the study group, but they do not provide a randomized comparison. A causal interpretation requires more than observing that measurements differ across time. The design and the absence of a reported analysis constrain what conclusions can be drawn from the registry entry.

The record also separates planning assumptions from evidence. The sample-size illustrations use a hypothetical equal-allocation, two-arm framework, while the trial is recorded as single group. Such illustrations are planning tools and should not be mistaken for trial findings or observed power. Together, these features make the study a useful example of reading outcome definitions, design, missingness, safety counts, and analysis reporting as distinct parts of the evidence.

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.

Numerical results for the primary pain endpoint are not reported in the registry record. There are no posted means, standard deviations, estimates of change, confidence intervals, or p-values for the described assessment times. The listed secondary outcomes also have no numerical results. This prevents assessment of outcome magnitude, variability, and precision.

The study has a single-group design, with no randomized control comparison. Consequently, changes across the assessment period cannot be interpreted as a controlled contrast. Masking is listed as none, and the record does not describe additional safeguards against measurement or observer influences.

One patient did not complete assessments after recovery of responsiveness, but the exact missing measurements and the method used to handle them are not reported. The recorded enrollment is 16, whereas the arm description states 15 subjects; the reason is not provided. The registry does not define the analysis population, so the number contributing to each endpoint cannot be established from the record.

The statistical analysis plan, model for repeated measurements, multiplicity approach, and sample-size justification are not reported. The stated planning assumptions describe an illustration based on an observed effect, not the trial's single-group design. The registry also does not detail eligibility criteria, participant characteristics, EEG analysis methods, or the scope of safety monitoring. These omissions limit both statistical appraisal and the context available for interpreting the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: EEG Studies of Ketamine General Anesthesia — NCT03553758.
• Registry record last updated 2020-08-26; status last verified 2020-08.
• Results first posted 2020-08-26.
• 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

The registry lists NCT03553758, titled “EEG Studies of Ketamine General Anesthesia,” as a completed phase 2 and phase 3 single-group study sponsored by Massachusetts General Hospital. It records ketamine as the drug intervention, anesthesia as the condition, enrollment of 16, and no masking. The arm description states that 15 subjects underwent ketamine general anesthesia.

The primary outcome is average pain intensity before and after induction, measured with PROMIS Pain Intensity 1a using a pre-calibrated pain cuff. Assessments are described before induction and at 30, 60, 75, and 120 minutes afterward. The registry lists 3 outcome measures and 0 analyses. Numerical outcome results and the statistical analysis plan are not reported. One patient did not complete assessments after recovery of responsiveness. The adverse-event record lists 0 serious events, 0 other events, and 0 deaths in the recorded group.