Anesthesia During Neurophysiologic Monitoring in Scoliosis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anesthesia During Neurophysiologic Monitoring in Scoliosis Patients (NCT01549873), a randomized na study. The primary outcome is Amplitude Required to Elicit the MEP.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with no masking. It lists idiopathic scoliosis as the condition and Nationwide Children's Hospital as the sponsor. The study began in 2012-01, reached primary completion in 2013-04, and is listed as completed. The listed enrollment is 30. The phase is recorded as not applicable.

Participants were assigned to TIVA or inhaled anesthesia. Propofol and desflurane are listed as the interventions. The arm descriptions do not include further regimen details. The registry summary explains that the investigators measured MEP and SSEP during spinal surgery and compared the two anesthesia approaches. It also notes that the hospital typically used inhaled anesthesia and was able to obtain these measurements. That background is not itself a trial result.

The primary outcome was the amplitude required to elicit the MEP at the time of surgery. The registry reports a mean and standard deviation for each arm. Two secondary outcomes are listed: SSEP amplitude and SSEP latency, each measured on the day of surgery. The primary outcome results report 15 participants in the TIVA arm and 14 in the inhaled-anesthesia arm. The adverse-event results list 15 at risk in each arm. The reason for the differing reported counts is not reported in the registry record.

The registry record does not report the randomization sequence method, allocation concealment, detailed eligibility criteria, participant flow, or the trial's original sample-size justification. It also does not report masking procedures beyond listing the trial as unmasked.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Amplitude Required to Elicit the MEP, measured over at time of surgery.

The primary endpoint is the amplitude required to elicit the MEP, measured in milliamperes at the time of surgery. An MEP is a response recorded during neurophysiologic monitoring after stimulation; the endpoint captures the stimulation amplitude associated with eliciting that response. The registry describes it as a measure used to compare neuromonitoring data between the anesthesia groups.

Comparing a continuous measurement between randomized groups can describe how the recorded stimulation requirement differed under the two anesthesia approaches in this trial. The arm means and their standard deviations describe the observed values and their variability. The mean difference gives the contrast between the group averages, while its confidence interval conveys uncertainty about the estimated contrast.

The registry record does not provide a clinical threshold for interpreting a difference in this measure, nor does it report how the endpoint was operationally measured beyond its definition and timing. The results therefore describe the posted MEP amplitude measure; they do not, by themselves, establish what size of difference would be clinically important or what it would mean for patient outcomes.

7. Results Posted in the Registry

• Inhaled Anesthesia: mean 417.00 versus 307.00 on control; difference 110.00 (95% CI 53.67 to 166.33), standardized effect d = 1.43; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Amplitude of the SSEPs

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Inhaled Anesthesia: mean 0.84 versus 0.83 on control; difference 0.01 (95% CI -0.23 to 0.25), standardized effect d = 0.03; z-test p = 0.935.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inhaled Anesthesia and the control. The interval gives the range of effects that remain compatible with the data.

Latency of the SSEP's

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Inhaled Anesthesia: mean 28.20 versus 27.60 on control; difference 0.60 (95% CI -0.82 to 2.02), standardized effect d = 0.31; z-test p = 0.408.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inhaled Anesthesia and the control. The interval gives the range of effects that remain compatible with the data.

The two secondary outcomes examine different aspects of SSEP recordings: amplitude and latency. Taken together, their posted estimates do not show the same pattern as the primary MEP amplitude comparison. The secondary comparisons are centered close to no mean difference, and their confidence intervals include zero. Their unadjusted p-values do not indicate strong evidence of a difference under the corresponding null comparisons.

These results complement the primary finding by showing that the posted MEP amplitude comparison did not coincide with a similarly clear contrast in the listed SSEP measures. That is a description of the observed endpoint pattern, not proof that the anesthesia approaches have identical effects on SSEP measurements. The secondary estimates have uncertainty, and the registry record does not provide a clinically important threshold for either measure.

Secondary outcomes usually carry less interpretive weight than a primary outcome, particularly when the analysis plan and multiplicity strategy are not documented. In general, examining several outcomes creates more opportunities for chance findings if each is assessed independently. The registry record lists two secondary measures but does not report whether they were prespecified in a detailed analysis plan, whether any adjustment was intended, or whether additional analyses were conducted. The posted comparisons are unadjusted.

The secondary findings should therefore be read as supportive descriptive information rather than as definitive tests of equivalence or absence of effect. A confidence interval spanning zero means the observed data and method are compatible with no difference as well as with some nonzero differences within the interval. It does not establish that the groups are the same. More complete interpretation would require a prespecified framework, suitable precision for meaningful differences, and clear reporting of missing data and analysis methods, none of which is fully available in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Amplitude of the SSEPs
• Latency of the SSEP's

9. Statistical Interpretation

10. Statistical Methods Explained

What does a comparison of means describe?

For a continuous outcome, a group mean is the arithmetic average of the recorded measurements in that group. The primary outcome is continuous and is reported as a mean with a standard deviation. The mean summarizes the center of the observed values; the standard deviation describes how spread out those values are around the mean. Neither measure describes the full distribution, and a mean difference does not imply that every participant had a response equal to the group average.

The posted comparison is expressed as a mean difference for inhaled anesthesia relative to TIVA. Its estimate is 110.0 milliamperes. A positive value in this direction corresponds to a higher reported mean in the inhaled-anesthesia arm. Keeping the contrast direction explicit matters: reversing the order of the groups would reverse the sign while leaving the underlying comparison unchanged.

How should the p-value be understood?

The unadjusted p-value for the primary comparison is <0.001. In general, a p-value measures how incompatible the observed data are with a specified null model, under the assumptions used to calculate it. A small p-value is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The registry record does not identify the specific test, its assumptions, or a complete analysis plan, so the test procedure should not be inferred from the reported summary statistics.

The word “unadjusted” indicates that the posted p-value is not presented as adjusted for multiple comparisons. The registry lists secondary outcomes as well as the primary endpoint, but it does not report a multiplicity strategy. As a general statistical principle, considering several outcomes or comparisons can increase the chance of at least one apparently unusual result when each is assessed separately. This is one reason to give the prespecified primary endpoint more interpretive weight than exploratory or unadjusted secondary findings.

What does the standard deviation contribute?

The primary standard deviations are 72.0 in the TIVA arm and 82.0 in the inhaled-anesthesia arm. They characterize within-arm variability, whereas the standard error characterizes uncertainty in an estimated quantity such as a mean. A spread of participant measurements and uncertainty about the group mean are related but not interchangeable. The registry comparison also reports standard errors for the arm means, but the record does not describe the calculation procedure or whether any additional modeling was used.

In general, variability matters because greater variation makes a group contrast harder to estimate precisely when the amount of information is otherwise similar. Small samples can also make estimates sensitive to individual observations. The registry record does not provide participant-level values, distribution plots, or diagnostics, so the impact of unusual observations and the shape of the outcome distribution cannot be assessed from the posted summaries.

What can be inferred from the design and analysis record?

Randomized allocation is intended, in general, to support a comparison by reducing systematic differences in baseline characteristics between groups. Whether that goal was achieved in this trial cannot be assessed fully from the information reported: baseline characteristics and details of the randomization process are not reported in the registry record. The record lists no masking, so participants and study personnel were not described as masked. It does not explain whether outcome assessors or analysts were masked.

The reported comparison is accompanied by a confidence interval and an unadjusted p-value, but the registry lists no reported analyses. A detailed statistical analysis plan, including the precise test, covariate adjustment, handling of missing outcomes, and analysis population, is not reported in the registry record. These omissions limit assessment of whether the posted analysis followed an original prespecified plan. No discrepancy is flagged for the posted calculations, but this does not supply the missing methodological details.

As a general principle, statistical significance and precision are different ideas. The p-value relates to compatibility with a null model under specified assumptions. The confidence interval gives a range of estimates compatible with the data and method, and helps show the uncertainty around the estimated mean difference. Neither alone resolves questions about clinical importance, measurement quality, or generalizability.

11. Confidence Intervals and Precision

The primary mean difference is 110.0 milliamperes, and its 95% confidence interval extends from 53.67 to 166.3. The interval expresses uncertainty in the estimated difference under the method used to construct it. It is not a range containing a stated proportion of individual participants' measurements, and it is not a guarantee that the true effect lies within those limits.

For the stated contrast— inhaled anesthesia minus TIVA—the full interval is positive. The limits therefore indicate that the posted comparison is not centered near zero and that the estimated direction is consistent across the reported interval. The width of the interval still matters: estimates within its limits represent meaningfully different sizes of group-mean contrast. The registry record does not state what difference would be clinically important.

In general, confidence intervals reflect both the observed estimate and its uncertainty. More information can often make an interval narrower, while greater variability can make it wider, though the exact result depends on the analysis. The primary outcome results report 15 participants for TIVA and 14 for inhaled anesthesia, with standard deviations of 72.0 and 82.0, respectively. These figures provide context for the precision but do not reveal the distribution of individual values.

The interval should be interpreted alongside the study's reporting limits. The registry does not report the exact confidence-interval method, missing-data handling, or a full statistical analysis plan. The interval describes precision for the posted mean comparison; it does not account for every possible source of uncertainty, such as measurement procedures or limitations in how participants were selected.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning figures are illustrations based on the observed effect, not the trial's original design justification. The trial's own sample-size assumptions are not reported in the registry record. The planning assumptions listed are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each scenario uses a stated fraction of the observed effect as the effect to detect.

All figures for these continuous outcomes are participants per arm, not totals across both arms. The planning rows describe detecting 100%, 75%, or 50% of the observed effect. The 80% power column gives the estimated participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true one. The 90% power column gives the corresponding estimate for a 90% chance. These are planning probabilities conditional on assumptions, not guarantees for a future study.

Smaller effects require more participants to detect with the same power and significance level. This general pattern is reflected in the planning scenarios, where the participant requirements increase as the target effect becomes a smaller fraction of the observed effect. The estimates rely on the observed effect, which can be uncertain, especially in a small trial. They should not be treated as a validated estimate of the effect a future study would encounter.

These figures are not observed power. They are prospective planning illustrations derived from the posted effect and the stated assumptions. They do not describe the probability that this completed trial detected an effect, nor do they replace the uncertainty shown by the confidence interval.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 110.000; pooled standard deviation σ = 76.977.
2. n = 2 × (1.96 + 0.842)² × 76.977² / 110.000² = 7.7, rounded up to 8 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 110                      # observed difference in means
sigma <- 76.9771490864755                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1549873)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 8 (80% power), 11 (90% power)
 75% of observed effect: n per arm = 14 (80% power), 19 (90% power)
 50% of observed effect: n per arm = 31 (80% power), 42 (90% power)
power.t.test: 8.8 
Simulated power at n = 8 per arm: 0.756 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and two secondary outcomes. It does not report a multiplicity adjustment or a hierarchy for interpreting the secondary outcomes. The primary comparison has an unadjusted p-value, and the secondary comparisons are also unadjusted. In general, when multiple outcomes are tested separately, the chance of at least one apparently notable result can increase. The size of that concern depends on the analysis plan and relationships among outcomes, details that are not reported in the registry record.

The record lists no reported analyses. It does not report whether the investigators planned to adjust for baseline characteristics, how the primary comparison was to be analyzed, or how any deviations from a planned analysis would be handled. The exact statistical test is also not reported. These missing details make it difficult to determine how closely the posted summaries reflect a prespecified analysis.

Missing-data handling and analysis populations are not reported in the registry record. The primary results list 15 participants for TIVA and 14 for inhaled anesthesia, while the listed enrollment is 30. The adverse-event results list 15 at risk in each arm. The reason for these differences in reported counts, and whether outcome data were missing or excluded, is not reported. It would be inappropriate to infer the number or reasons for any missing observations from these counts alone.

The registry record does not describe whether the analysis used an intention-to-treat population, a per-protocol population, or another definition. It also does not report the number randomized by arm, withdrawals, exclusions, or participant flow. These omissions matter because the population used for analysis can affect the interpretation of a randomized comparison. The posted results remain informative as reported summaries, but a fuller assessment of multiplicity, missingness, and analysis populations is not possible from the registry record.

15. 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 adverse-event results list 15 participants at risk in each arm. For serious adverse events, the posted count is 0 in the TIVA arm and 0 in the inhaled-anesthesia arm. For other adverse events, the posted count is also 0 in each arm. The registry lists no serious adverse-event terms.

These figures describe the adverse-event counts recorded in the registry; they do not establish that no events occurred beyond what was reported or that the two approaches have equivalent safety. The registry record does not provide further details about event definitions, surveillance procedures, duration of follow-up, or completeness of adverse-event reporting. Death counts are not reported in the registry record.

With a small number of participants reported at risk, zero recorded events should be interpreted as an absence of reported events in these data, not as proof that an event cannot occur. Safety interpretation depends on how events were collected and on the amount of follow-up, details that are not reported in the registry record.

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

The posted results show that the mean amplitude required to elicit an MEP was higher in the inhaled-anesthesia group than in the TIVA group in this trial. The estimated mean difference is 110.0 milliamperes, with a 95% confidence interval from 53.67 to 166.3 and an unadjusted p-value of <0.001. This describes the recorded endpoint under the trial conditions.

The result does not establish that one anesthesia approach is better overall, nor does it show that a higher or lower stimulation amplitude leads to a difference in patient health or surgical outcome. The registry's question concerns the measurement of MEP and SSEP. It does not report an outcome that directly assesses broader clinical benefit, nor does it define a clinically important difference in the MEP amplitude measure.

The secondary SSEP results do not provide a clear parallel signal in the posted comparisons, but they do not prove equivalence between the approaches. The registry does not report an equivalence margin or a plan designed to establish equivalence. Likewise, a non-significant secondary comparison is not evidence that the true difference is exactly zero.

The randomized design supports a comparative interpretation, but limitations in reporting leave important questions unresolved. Details of randomization, baseline characteristics, analysis populations, missing-data handling, and the full analysis plan are not reported in the registry record. The differing participant counts across the primary outcome and safety results are not explained. The findings should be understood within this reporting context and should not be generalized beyond the studied setting without additional evidence.

17. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between an outcome-specific difference and a broad claim about treatment. The primary endpoint is a continuous measure of stimulation amplitude during neuromonitoring. Its mean comparison can quantify how the recorded measure differed across randomized groups, but it does not by itself answer whether that difference matters to patients or to surgical outcomes.

The reported primary estimate is accompanied by a confidence interval and an unadjusted p-value, allowing readers to consider both direction and precision rather than relying on a significance label alone. The secondary results provide a contrasting pattern: their estimates do not show a similarly clear group difference. That contrast makes it important to distinguish the endpoint that was designated primary from additional measures that may be less well protected against multiple-comparison concerns.

The record also demonstrates why statistical interpretation depends on reporting quality. Randomization is stated, but the method and allocation procedures are not described. The registry does not report a full analysis plan, analysis populations, missing-data procedures, or multiplicity handling. These details help readers judge whether the statistical comparisons were prespecified and how robustly they reflect the trial design.

Finally, the sample-size illustrations show how planning depends on the effect size a future study aims to detect and on stated design assumptions. They are not a substitute for the trial's original justification, which is not reported in the registry record. Taken together, the trial offers a focused comparison of monitoring measurements while underscoring the limits of interpreting statistical results without broader methodological and clinical context.

18. 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.

Several trial-specific limitations affect interpretation. The registry reports a randomized design but does not describe how the sequence was generated or how allocation was concealed. It lists no masking, and does not specify whether outcome assessors or data analysts were masked. Baseline characteristics and detailed eligibility criteria are not reported, so balance between groups and the population represented by the results cannot be assessed from the registry record.

The listed enrollment is 30, while the primary outcome results list 15 participants in the TIVA arm and 14 in the inhaled-anesthesia arm. The adverse-event results list 15 at risk in each arm. The reasons for these reporting differences are not reported. Participant flow, withdrawals, missing outcome data, and analysis populations are also not described.

The registry record lists no reported analyses and does not provide a detailed statistical analysis plan. The exact test, any planned covariate adjustment, multiplicity strategy, and missing-data procedures are not reported. The reported secondary results are unadjusted, so they should be interpreted cautiously alongside the primary outcome.

The record does not report detailed anesthesia protocols, measurement procedures, or the clinical importance of a difference in the primary endpoint. It also does not report follow-up beyond the surgery-time or day-of-surgery measurements. These limits constrain interpretation to the posted monitoring measures and prevent conclusions about longer-term or broader clinical outcomes.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Anesthesia During Neurophysiologic Monitoring in Scoliosis Patients — NCT01549873.
• Registry record last updated 2015-02-26; status last verified 2015-02.
• Results first posted 2015-02-26.
• 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.

22. Record Summary

The registry record describes a completed, randomized, parallel-group trial with no masking, sponsored by Nationwide Children's Hospital. It lists idiopathic scoliosis, enrollment of 30, and a study period beginning in 2012-01 with primary completion in 2013-04. The comparison was TIVA, with propofol listed, versus inhaled anesthesia, with desflurane listed.

The primary outcome was the mean amplitude required to elicit an MEP at surgery. The posted mean difference favored a higher measured amplitude in the inhaled-anesthesia arm, with a confidence interval that excludes zero. Two secondary SSEP outcomes were also posted, without similarly clear evidence of a group difference.

The registry does not report a detailed statistical analysis plan, analysis populations, missing-data handling, or multiplicity procedures. The reasons for differences in the reported participant counts are not reported in the registry record. The results describe neuromonitoring measurements and should not be taken as evidence about broader clinical outcomes.