Effects of IV Administration of Ketamine on the Analgesia Nociception Index (ANI) Measured With the PhysioDoloris: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of IV Administration of Ketamine on the Analgesia Nociception Index (ANI) Measured With the PhysioDoloris (NCT01717521), a registered phase not stated study. The primary outcome is Mean ANI Changes After Intubation.

2. Clinical Question

ANI is a dimensionless index generated by a pain monitor. The registry describes its range as 0–100, with 100 indicating absent pain and lower values corresponding to greater pain. The study therefore focused on a monitor-derived measure rather than a directly reported pain rating. Its primary endpoint is listed as mean ANI changes after intubation, with the timeframe described as before versus after intubation.

This question is narrower than whether ketamine changes pain or improves patient outcomes. The registry record does not report an untreated or placebo comparison, and the primary time comparison is between measurements around intubation. It also does not report numeric endpoint results. Consequently, the record supports describing the question and measurement, but not estimating the change or attributing any change specifically to ketamine.

3. Trial Design

The record describes a completed pilot study sponsored by the University of Washington. It lists a start date of 2012-08 and a primary completion date of 2012-12. The recorded enrollment is 20, and the study population is described as women undergoing abdominal hysterectomies. The listed condition is intraoperative monitoring.

The study is identified as a single group with intervention. Allocation is not stated, and the record explicitly does not present a randomized, like-for-like control comparison. The primary endpoint uses a before-and-after time comparison around intubation. That is a within-study time contrast, not a comparison between ketamine and a separate control treatment. The record does not explain whether the same measurement schedule or any other protocol features were used beyond the stated timeframe.

The study title and summary identify intravenous ketamine and evaluation of its effects on ANI measurements. The record also lists secondary outcomes concerning BIS, heart rate, and mean arterial pressure at specified perioperative events, including intubation, a ketamine bolus, and skin incision. These listed outcomes describe the study’s measurement scope; numeric results for them are not reported in the registry record.

The record lists 14 outcome measures but contains no entered analysis records. It does not report a detailed statistical analysis plan, randomization procedures, masking, eligibility criteria, or a sample-size justification. Those design details should not be inferred from the single-group label, the pilot description, or the listed endpoints. The completed status indicates the registry’s recorded status, but by itself does not establish what analyses were conducted or whether all planned measurements were available.

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

Analysis population for the primary outcome, as defined in the registry: This pilot study included 20 women undergoing abdominal hysterectomies

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: Twenty women, 18 years of age or older, of American Society of Anesthesiology Physical Status I-III scheduled for an abdominal hysterectomy under sevoflurane anesthesia were recruited.

6. Primary Endpoint

The registry lists the primary outcome as Mean ANI Changes After Intubation, measured over Before vs after intubation.

The primary endpoint is mean change in ANI after intubation, with the comparison described as before versus after intubation. ANI stands for Analgesia Nociception Index. The registry describes it as a dimensionless monitor-derived value ranging from 0–100; a value of 100 indicates absent pain, and lower values correspond to greater pain. This makes the endpoint a physiological monitoring index, not a direct report of a participant’s subjective pain.

A mean summarizes the central level of a continuous measurement across observations. A change endpoint focuses on how measurements differ across the stated time points. For a before-and-after measure, interpretation depends on how the observations are paired and how the change is defined; the registry record does not give those analytic details. It identifies standard deviation as the dispersion measure for the primary outcome, which describes variation in the measurements around their mean.

Monitoring ANI around intubation can be used to describe how the index behaves during a defined perioperative event. However, the record does not provide the mean values, mean change, standard deviation, or a confidence interval. The size, direction, and precision of the endpoint therefore cannot be evaluated from the registry record. Nor does an ANI change alone establish a change in patient-experienced pain or a causal effect of ketamine.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the endpoint’s scale and design. ANI is described as a continuous, dimensionless index ranging from 0–100. The primary outcome is a mean change around intubation, rather than a binary event count or time-to-event outcome. For a continuous endpoint, a mean describes the central value, while a standard deviation describes spread around that mean. These quantities answer different questions: the mean characterizes the average measurement or change, and the standard deviation characterizes variability among measurements.

What does a mean change represent?

A change score compares measurements at two stated times. In a before-and-after design, the natural unit of analysis may be each participant’s own change, because the measurements are taken on the same person. An analysis of paired changes can account for the fact that measurements from one person may be more alike than measurements from different people. A comparison that treats the two time points as independent would not make that allowance. The registry record names a before-versus-after timeframe but does not report how the change was calculated or which statistical test was used, so the actual analytic approach cannot be confirmed.

For paired measurements, the spread of individual changes is not necessarily the same as the spread of measurements at either time point. The standard deviation attached to a mean change would describe variability in the change values if that is how it was calculated. The record identifies standard deviation as the dispersion measure, but does not provide its value or explain exactly which measurements it summarizes. Without a reported estimate and its variability, neither the typical change nor variation among participants can be assessed.

What would uncertainty add?

A confidence interval is a range expressing uncertainty around an estimated effect under the assumptions of the analysis. A narrow interval generally indicates greater precision than a wide interval, although interpretation also depends on the endpoint and study design. A confidence interval can help readers distinguish a precise estimate from one that is uncertain. The registry record does not report a confidence interval for the primary outcome. It also does not report a test statistic or p-value for that outcome, so the statistical evidence cannot be reconstructed from the posted record.

A p-value, in general, measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions are correct. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. Because no primary result or p-value is reported, there is no basis for describing statistical significance. In any event, significance alone would not show that an effect is large, precisely estimated, or attributable to ketamine.

Why does the single-group design matter?

The primary contrast is before versus after intubation in a single group with intervention. A within-person comparison can describe the time-related change among the observed participants, but the record does not identify a separate group receiving no ketamine or another comparator. Without such a comparison, changes associated with the intervention cannot be separated from changes associated with the procedure or other events occurring over time. This is a design limitation for causal interpretation, regardless of the statistical method used.

The registry lists secondary measures at several perioperative events, including measures related to intubation, ketamine bolus, and skin incision. Repeated measurements can be correlated within a participant, and analyses of multiple outcomes or time points may need to account for that dependence. General statistical practice also considers the risk of chance findings when many outcomes are examined. The registry record does not report whether repeated-measures methods, multiplicity adjustments, or another approach were used.

How should the planning assumptions be read?

The record describes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect is a planning target defined relative to the observed effect; it is not a new observed result. Such an illustration estimates a hypothetical sample size under its assumptions. It is not observed power and does not change what was measured in the completed single-group study.

The illustration’s assumptions describe a hypothetical two-arm design, whereas the trial record describes one group with intervention and no like-for-like control comparison. The registry record does not report the numeric illustration estimates or the observed primary effect needed to assess them. It also does not report a trial-specific sample-size justification. Accordingly, the illustration should be read as a planning exercise, not as evidence that this study was designed or analyzed as a two-arm trial.

Over-dispersion is a general concern when variability exceeds what a chosen statistical model assumes. If a model understates variability, standard errors and uncertainty intervals may be too small, making results appear more precise than warranted. The primary outcome is continuous, and the record identifies standard deviation, but does not provide enough information to evaluate the distribution of the measurements or whether any model assumption was checked. Thus no claim about over-dispersion or model adequacy can be made for this study.

Overall, the statistical methods that were actually used are not reported in the registry record. General principles clarify what mean changes, standard deviations, confidence intervals, and planning calculations would mean, but they cannot substitute for the missing endpoint values and analysis description.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Single Group")
n   <- c(20)
m   <- c(2.11)
sp  <- c(20.11)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Single Group  20  2.110  20.110  -7.302  11.522

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including the primary ANI outcome and secondary outcomes concerning BIS, heart rate, and mean arterial pressure. It does not provide numeric results for these measures or analysis records. The registry record does not report whether a hierarchy among outcomes was prespecified, whether statistical tests were adjusted for multiple comparisons, or how outcomes were selected for reporting.

Multiplicity matters when many outcomes or time contrasts are examined: the chance of at least one apparently notable result can increase when multiple tests are conducted. This is a general statistical consideration, not a claim that a particular adjustment was needed or omitted in this study. Without the analysis plan and results, the handling of multiplicity cannot be evaluated.

The record also does not report missing-data counts, reasons for missingness, or the method used to handle missing measurements. Enrollment alone does not show how many participants contributed data to each endpoint. No analysis population is described, and the record does not state whether all enrolled participants were included in each analysis. These details are important for understanding the denominator behind an estimate and for assessing possible bias due to incomplete measurements.

The absence of analysis entries in the registry record should not be interpreted as proof that analyses were not performed. It indicates that the posted record does not document those analyses. A statistical plan, missing-data description, and outcome-specific results are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists one intervention group and reports 20 participants at risk for serious adverse events, with 0 serious adverse events. It also reports 20 participants at risk for other adverse events, with 0 other adverse events. These are the registry’s posted event counts for the categories shown.

The death count is not reported in the registry record. The listed zero event counts do not establish that no event could occur, nor do they show that the intervention is free of risk. In a small pilot study, an absence of recorded events is limited evidence about uncommon harms, and the record does not provide event definitions, surveillance procedures, follow-up duration, or a detailed safety analysis.

These figures should be read as descriptive registry entries, not as a comparative safety estimate. The study is recorded as a single group with intervention, and no control-group event counts are reported. Therefore, the event counts cannot establish whether risk differed from another treatment or from no intervention. They also do not address the primary ANI endpoint or establish a clinical benefit.

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

The registry record establishes that this completed pilot study examined ANI around intubation in women undergoing abdominal hysterectomies, in the context of intravenous ketamine administration. It identifies the endpoint, its measurement scale, and the stated before-and-after timeframe. It also describes the study as a single group with intervention and lists related perioperative outcomes.

What the record does not establish is the numeric result. No mean ANI change, standard deviation, confidence interval, or p-value is reported. The direction, magnitude, and precision of the primary change are therefore unknown from the registry record. The listed outcome titles are not substitutes for outcome estimates. Nor can the result be reconstructed from the enrollment or the endpoint description.

Even if a before-and-after change were reported, that contrast would describe change over time in the measured group. Without a separate comparison group, it would not isolate ketamine’s effect from intubation or other concurrent perioperative influences. The record also does not report a connection between ANI values and patient-reported pain in this study. The monitor’s scale description should not be stretched into a claim about clinical benefit or harm.

The safety entries record 0 serious adverse events and 0 other adverse events in the listed group, while the death count is not reported. Those entries are descriptive and do not establish comparative safety. The record’s completed status does not fill in the missing outcome estimates or analysis details.

In short, the registry record identifies the question and the measurement, but it does not support a quantitative conclusion about the observed ANI change or a causal conclusion about ketamine. The study should be interpreted as a pilot record with outcome results and key analysis details not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically instructive because it distinguishes a clearly named measurement from a fully interpretable result. The registry defines ANI and identifies a before-and-after primary endpoint, but without the mean change and its variability, readers cannot estimate the size or precision of the measured change. Endpoint definitions are necessary for interpretation, but they are not a substitute for numeric findings.

The single-group structure also highlights the difference between observing change and attributing change. Measurements around intubation can describe what happened over time in the group studied. Without a separate comparison group, however, the record cannot isolate a ketamine effect from the procedure or other events. That distinction matters even when the outcome is measured objectively by a monitor: an objective measurement does not, by itself, create a causal comparison.

The record lists multiple outcome measures, yet does not document analysis entries, missing-data handling, or multiplicity procedures. These omissions show why transparent reporting includes more than an outcome name and a study status. Analysis methods, denominators, uncertainty estimates, and the treatment of multiple outcomes help readers evaluate the strength and limits of evidence.

Finally, the planning assumptions describe a hypothetical sample-size illustration, not an observed result or observed power. Keeping planning calculations separate from trial findings is important because assumptions about a future design cannot answer what the completed study found. Here, the registry record supports understanding the study’s statistical question and design constraints, while leaving its quantitative answer unavailable.

15. 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 numeric results for the primary endpoint are not reported in the registry record. The mean change, standard deviation, and any confidence interval or test result are absent. The direction, size, variability, and precision of the measured change therefore cannot be assessed.

The study is described as a single group with intervention, with allocation not stated and no like-for-like control comparison. The primary timeframe is before versus after intubation. This structure can describe a within-group time contrast but cannot isolate the effect of ketamine from the effects of intubation or other perioperative events. The record does not report further design details that might clarify the timing or conduct of measurements.

The population is described as 20 women undergoing abdominal hysterectomies, and the study is identified as a pilot. The registry does not report additional eligibility criteria or participant characteristics. The extent to which observations apply outside this described population cannot be assessed from the record.

Although 14 outcome measures are listed, the registry does not report their numeric results, an analysis plan, or analysis records. Missing-data handling, outcome-specific analysis populations, multiplicity procedures, and model checks are also not reported in the registry record. The recorded adverse-event counts are descriptive, and the death count is not reported. These limitations restrict both quantitative interpretation and assessment of the completeness of the posted evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of IV Administration of Ketamine on the Analgesia Nociception Index (ANI) Measured With the PhysioDoloris — NCT01717521.
• Registry record last updated 2019-08-05; status last verified 2019-06.
• Results first posted 2019-08-05.
• 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.

19. Record Summary

The University of Washington sponsored a completed pilot study of intravenous ketamine and ANI monitoring, recorded as NCT01717521. The registry lists enrollment of 20 and describes women undergoing abdominal hysterectomies. The start date is 2012-08, and the primary completion date is 2012-12.

The primary endpoint is mean ANI change after intubation, with a before-versus-after timeframe. ANI is described as a dimensionless index ranging from 0–100, where 100 indicates absent pain and lower values correspond to greater pain. The study is recorded as a single group with intervention, not a randomized comparison.

The record lists 14 outcome measures but no analysis records. Numeric primary and secondary outcome results, analysis details, missing-data methods, and a trial-specific sample-size justification are not reported in the registry record. The listed safety counts are 0 serious adverse events and 0 other adverse events; the death count is not reported.