Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine (NCT00671931), a randomized phase 1 study. The primary outcome is Motor Evoked Potential Amplitude.

2. Clinical Question

The clinical context is intraoperative monitoring of neurological structures during scoliosis surgery. The registry describes these signals as important for informing the surgical team about spinal-cord integrity, and notes that anesthetic regimens can affect monitoring modalities. Its stated hypothesis is that clinically relevant dexmedetomidine blood levels could affect transcranial motor-evoked-potential amplitude either independently or through interaction with propofol.

The trial therefore addresses a measurement and anesthetic-exposure question, rather than reporting a comparison of surgical or long-term neurological outcomes. The endpoint captures a substantial decrease in an electrophysiological signal against each participant’s baseline. Whether the five combinations produce different rates of that event is a statistical question, but the registry record gives counts by group without comparative estimates, confidence intervals, or tests.

3. Trial Design

The registry identifies this as a completed phase 1, randomized, unmasked, factorial study with enrollment of 44. The recorded condition is scoliosis. The start date is 2007-04 and the primary completion date is 2009-01. The sponsor is Children's Hospital Medical Center, Cincinnati. Additional details about the recruitment setting and participant eligibility are not reported in the registry record.

Five groups are listed: low dexmedetomidine with low propofol; high dexmedetomidine with low propofol; low dexmedetomidine with high propofol; high dexmedetomidine with high propofol; and intermediate levels of both drugs. The reported group sizes are 8, 8, 9, 8, and 7 participants, respectively. The record labels the design factorial, consistent with variation in levels of two drugs, but does not describe the allocation procedure, sequence generation, concealment, or the intended factorial contrasts.

Randomization means allocation is intended to reduce systematic differences between groups, but it does not guarantee that groups are alike in every characteristic, particularly in a small study. The study was unmasked. The registry does not state whether participants, clinicians, outcome assessors, or analysts knew treatment allocation, nor whether any procedures were used to reduce assessment bias.

The primary outcome timeframe is described as baseline and 30 minutes. The registry does not give further detail on the timing of drug administration in relation to the measurement, how the targeted blood levels were achieved or confirmed, or whether additional measurements were taken. The protocol’s dose levels, study procedures, sample-size justification, and planned statistical model are not reported in the registry record. These omissions limit the extent to which the design can be reconstructed from the posted record alone.

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: There is no wash out, run-in, or transition period in this protocol

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 Motor Evoked Potential Amplitude, measured over baseline, 30 minutes.

The primary endpoint is the number of participants whose motor-evoked-potential amplitude was reduced by more than 70% compared with baseline. The registry lists measurements at baseline and 30 minutes and describes the outcome in terms of participants, making the posted result a count of participants meeting a threshold rather than a continuous summary of amplitude values.

Transcranial motor-evoked potentials are electrophysiological signals used in the monitoring context described by the registry. Comparing amplitude with baseline focuses the outcome on a change in the signal within a participant. A prespecified threshold can make a potentially important signal reduction easier to count and compare across groups. It also discards detail: a participant just beyond the threshold and one with a much larger reduction are both counted as events, while changes not crossing the threshold are not counted as events.

The record does not explain why the more-than-70% threshold was selected, whether it was established before data collection, or how amplitude was measured and summarized when there were repeated signals. It also does not report continuous amplitude results, participant-level changes, or measurement variability. Thus, the posted counts describe how many participants crossed the stated threshold; they do not show the full distribution of amplitude changes or establish the cause of any change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods needed to interpret this study depend on the endpoint’s form and the multi-group design. The registry identifies the outcome as a count of participants with an event: a reduction in motor-evoked-potential amplitude by more than 70% relative to baseline. The available results give event counts and group sizes. They do not include inferential analyses, so the statistical concepts below are general explanations, not a description of analyses documented for this trial.

What does a binary endpoint represent?

General explanation: a binary endpoint classifies each participant into one of two categories, such as meeting or not meeting a defined threshold. The count of participants meeting the threshold is easy to describe, but it contains less information than the underlying measurements. Here, the endpoint does not distinguish the magnitude of reductions once the threshold is crossed. It also does not display changes that fall short of the threshold. Continuous amplitude data would be needed to examine the range and distribution of changes in more detail; such results are not reported in the registry record.

What can randomization and a factorial design contribute?

General explanation: random allocation can help make groups comparable on average, including with respect to characteristics that are not measured. In a factorial design, more than one intervention factor is varied, allowing questions about each factor and whether the factors interact. An interaction means that the effect associated with one factor may differ depending on the level of the other factor. The five recorded combinations vary dexmedetomidine and propofol levels, but the registry does not state the planned contrasts or statistical model. The label “factorial” alone is not enough to know how the investigators intended to estimate these effects.

Group-by-group comparisons and a factorial analysis answer different questions. A comparison between two groups can describe their contrast, while a factorial model may combine information across multiple groups to estimate a drug effect and interaction under specified assumptions. The record reports no such estimates or tests. It also does not describe whether any baseline factors were to be adjusted for, or how missing endpoint measurements would be handled.

Why are uncertainty estimates important?

General explanation: a confidence interval is a range of values compatible with the observed data under a specified statistical method. It communicates the precision of an estimate and helps distinguish a fairly precise estimate from one that remains uncertain. A p-value, when used, describes how compatible data are with a specified null hypothesis and model; it is not a measure of clinical importance and does not establish that a hypothesis is true or false. Neither confidence intervals nor p-values are reported for the comparisons in this registry record. With small groups and a binary event, uncertainty around group rates and contrasts can be considerable, but its size cannot be quantified from the posted inferential results because none are present.

What does the record say about the analysis plan?

The registry lists no analyses. It does not report the planned statistical test, model specification, significance threshold for the primary comparison, handling of multiple comparisons, or analysis population. The sample-size justification is also not reported in the registry record. It is therefore not possible to determine whether the study was designed to estimate a particular effect with a prespecified precision or to test a particular factorial hypothesis. A planning illustration based on an observed effect, when available, is not a substitute for the trial’s design justification and must not be interpreted as observed power.

The endpoint counts can be used to describe the participants recorded in each group, but a new inferential calculation would require choices about the comparison, method, and assumptions. No such recalculation is needed to read the registry’s descriptive results, and no new statistical result should be inferred from the counts alone. The record does not report whether an interim analysis was planned or performed. It also does not describe whether outcome assessors were masked, how repeated amplitude measurements were combined, or whether any data quality rules were applied.

For a reader, the practical distinction is between description and inference. The posted counts describe observed endpoint classifications. A statistical comparison would add an estimate of the contrast and uncertainty around it, using a method suited to a binary endpoint and the randomized multi-arm design. Because those estimates and methods are absent, the registry record supports a descriptive reading only. The hypothesized effects of dexmedetomidine, propofol, and their interaction cannot be evaluated from the posted analyses.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Low Dexmedetomidine/Low Propofol", "High Dexmedetomidine/Low Propofol", "Low Dexmedetomidine/High Propofol", "High Dexmedetomidine/High Propofol", "Intermediate Dexmedetomidine/Intermediate Propofol")
n      <- c(8, 8, 9, 8, 7)
events <- c(1, 3, 1, 4, 4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Low Dexmedetomidine/Low Propofol  8  1  12.5  0.3  52.7  2.2  47.1  2.8  48.2
ARM  High Dexmedetomidine/Low Propofol  8  3  37.5  8.5  75.5  13.7  69.4  13.7  70.1
ARM  Low Dexmedetomidine/High Propofol  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5
ARM  High Dexmedetomidine/High Propofol  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8
ARM  Intermediate Dexmedetomidine/Intermediate Propofol  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no secondary outcomes. It records zero analyses, so there is no reported set of primary or secondary statistical tests to evaluate. The intended primary contrast, any additional pairwise comparisons, and any adjustment for multiple testing are not reported in the registry record.

Multiplicity arises when several hypotheses or outcomes are tested. General explanation: when many tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the number and structure of the tests. This is especially relevant to a five-group design, where several comparisons could be considered. The record does not establish which comparisons were prespecified or whether any multiplicity procedure was planned. It would therefore be inappropriate to infer that the posted group counts represent a particular set of formal tests.

The record does not describe missing endpoint data or give an analysis population. The group sizes are reported, but the handling of participants without an evaluable measurement, withdrawals, protocol deviations, or exclusions is not stated. It is also not reported whether the analysis was intended to follow randomized assignment or to use another population definition. These details matter because exclusions or missing measurements can affect a comparison if they are related to treatment assignment or endpoint status.

No interim analyses, stopping rules, or missing-data methods are reported in the registry record. Their absence from the posted information does not establish that no such procedures existed; it means their use cannot be assessed from this record. The descriptive counts should therefore be interpreted alongside the limited information about analysis populations and data completeness.

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.

For serious adverse events, the registry reports zero affected participants in each of the five groups. The numbers at risk are listed as 8, 8, 9, 8, and 7 across the low/low, high/low, low/high, high/high, and intermediate/intermediate combinations, respectively. The registry also reports zero participants with other adverse events in each group, using the same group sizes.

These figures are counts recorded in the registry. They do not establish that an event was impossible, nor do they provide a precise estimate of event frequency beyond the participants and observation period recorded. The duration of safety follow-up, the method for collecting adverse events, and the criteria used to classify events are not reported in the registry record. Death counts are also not reported in the registry record.

The absence of reported affected participants in these groups should be read as a descriptive safety result for this study, not as proof that the drug combinations carry no risk. The small group sizes limit what can be learned about uncommon events. The registry lists no serious adverse-event terms, so there are no event descriptions to characterize further.

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

The results show that participants meeting the primary endpoint were recorded in each of the five anesthetic-combination groups. The posted counts range from 1 participant in two groups to 4 participants in two other groups; the intermediate-level group also has 4 recorded events. These figures describe the study observations at the stated threshold. They do not by themselves show that one combination caused more signal reductions than another.

The endpoint is a thresholded change from baseline at the recorded 30-minute timeframe. It is not a direct report of spinal-cord injury, postoperative neurological deficit, or a clinical outcome after surgery. The registry’s background explains why monitoring signals matter during scoliosis surgery, but the posted outcome counts should not be treated as evidence about surgical outcomes or patient benefit.

The study’s stated hypothesis includes both an independent dexmedetomidine effect and an interaction with propofol. Assessing those questions requires suitable comparisons and statistical estimates. Since no analyses are posted, the registry does not establish whether there is a dose-dependent pattern, whether propofol modifies an effect, or how precise any difference might be. Actual targeted blood levels are not reported, further limiting interpretation of the relationship between drug exposure and amplitude.

Likewise, the descriptive safety counts do not establish the absence of risk. They reflect the recorded participants, with no reported serious or other adverse events in the listed groups, but safety follow-up details and death counts are not reported in the registry record. The record supports cautious description of what was recorded, not a definitive claim about comparative efficacy, safety, or mechanism.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it combines two anesthetic factors and measures a signal that can be affected by the anesthetic regimen. The stated hypothesis is not limited to a simple difference between two treatments: it asks whether dexmedetomidine affects motor-evoked-potential amplitude and whether that effect depends on propofol. A factorial design can be suited to such questions when the contrasts and analysis are specified clearly.

The endpoint also illustrates the trade-off involved in turning a continuous measurement into a binary outcome. Counting participants whose amplitude reduction exceeds a threshold makes the result straightforward to describe, but it removes information about the size and pattern of changes. This distinction matters when interpreting event counts and considering what additional summaries would clarify the observed signal behavior.

The record’s main statistical limitation is that it provides group counts without comparative analyses. The study’s randomized design does not, on its own, reveal the precision of group contrasts or establish an interaction. Small group sizes make the descriptive counts sensitive to individual classifications, and the absence of confidence intervals or planned-model details leaves uncertainty difficult to characterize.

For clinical researchers, the record highlights the importance of prespecifying factorial contrasts, outcome definitions, analysis populations, and the handling of multiple comparisons and missing data. Those elements are not reported in the registry record. The trial therefore offers a useful example of how an informative research question and a randomized design can still leave key statistical interpretations unresolved when analysis methods and inferential results are 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 registry record does not provide detailed eligibility criteria, baseline characteristics, or information about the clinical setting. It identifies scoliosis as the condition but does not describe the participant population further. Generalizability to other populations or settings cannot be assessed from the record alone.

The five infusion combinations are named by relative levels, but actual infusion rates and targeted or measured blood concentrations are not reported in the registry record. This prevents direct interpretation of exposure levels and makes it difficult to assess the stated question about clinically relevant blood levels. The record also does not explain how those levels were selected or maintained.

Outcome measurement details are limited. The registry states the threshold and baseline-to-30-minute timeframe, but does not describe the amplitude measurement procedure, repeat-measurement handling, assessor masking, or rationale for the threshold. Continuous outcome summaries are not reported. Consequently, the counts do not convey the magnitude or distribution of signal changes.

Although the study is labeled randomized and factorial, details of the randomization process, allocation concealment, intended contrasts, and analysis model are not reported in the registry record. The record includes no comparative statistical analyses, uncertainty estimates, or sample-size justification. It also does not report missing-data methods, analysis populations, interim analyses, or multiplicity procedures. These gaps prevent a full appraisal of the planned and conducted statistical analysis.

Finally, the group sizes are small, and the record’s adverse-event reporting does not include follow-up duration or death counts. The posted zero counts cannot establish that events are absent beyond the observed study record. These limitations mean the results are best treated as descriptive evidence from the recorded participants, with comparative conclusions remaining unresolved.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine — NCT00671931.
• Registry record last updated 2013-08-23; status last verified 2013-08.
• Results first posted 2013-08-23.
• 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

This completed phase 1 trial is recorded as randomized, unmasked, and factorial, with enrollment of 44 and scoliosis as the condition. It compares five combinations of low, high, or intermediate dexmedetomidine and propofol infusion levels. The primary outcome is the number of participants whose motor-evoked-potential amplitude fell by more than 70% relative to baseline at the 30-minute assessment.

The posted event counts are 1 of 8, 3 of 8, 1 of 9, 4 of 8, and 4 of 7 across the five groups. The registry lists zero serious and zero other adverse events in each group. No statistical analyses are posted, and comparative estimates, confidence intervals, and p-values are absent. Actual blood levels, analysis methods, sample-size justification, analysis populations, and detailed missing-data procedures are not reported in the registry record. The counts therefore describe observed endpoint classifications but do not resolve the hypothesized drug effects or interaction.