Analgesic Effect of Peripheral Dexmedetomidine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Analgesic Effect of Peripheral Dexmedetomidine (NCT00971178), a randomized phase 3 study. The primary outcome is Pain Score at Rest.

2. Clinical Question

3. Trial Design

This is a Phase 3 randomized trial with a parallel-group design. The registry lists quadruple masking, indicating that the study was recorded as masked at four levels, but it does not identify those roles or explain how masking was maintained. The University of Hong Kong is the sponsor. The record gives a total enrollment of 105 and lists 33 participants in each of the three arms.

The study compares local dexmedetomidine with normal saline and includes a separate intravenous dexmedetomidine arm. The arm descriptions are blank, and the intervention entries do not state doses or administration schedules. Further details of allocation procedures, concealment, treatment delivery, and follow-up are not reported in the registry record.

The study start is recorded as 2006-02, primary completion as 2008-03, and status as completed. The clinical setting is bilateral third molar surgery under general anaesthesia. The primary outcome is pain score at rest measured across the postoperative 72 hours, summarized as an area under the curve. The registry describes the measure as continuous and reports group means and standard deviations.

The registry names a Kruskal-Wallis test for comparing the primary outcome among the three groups. However, it records no analyses and posts no result for that overall test. The pairwise mean differences and associated intervals and p-values discussed in the interpretation are unadjusted recalculations from the posted group summaries, not a substitute for the stated three-group analysis. The record does not report the original analysis plan, sample-size justification, or details of analysis populations.

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: The patients were assessed by the scheduled anesthesiologist the day before surgery, were fasted for at least 6 hours and did not receive any premedication before arrival at the operation room.

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 Pain Score at Rest, measured over 72 hours after surgery.

The primary endpoint is pain score at rest over 72 hours after surgery. The registry describes assessment with the Numerical Rating Scale, where 0 corresponds to no pain and 10 to the worst pain imaginable. It summarizes the repeated pain scores over postoperative 72 hours as an area under the curve, calculated using the trapezoid rule. The reported unit is score on a scale×hr.

An area under the curve combines measurements across the stated follow-up period into a summary that reflects the pattern of scores over time. This can represent the overall burden of recorded pain rather than relying on a single assessment. General statistical interpretation: such a summary depends on the timing and completeness of the repeated measurements, as well as on the calculation method. The registry names the trapezoid rule but does not report the individual measurement schedule or how missing score assessments were handled.

The registry says the three groups were to be compared using the Kruskal-Wallis test. That is a rank-based method for assessing whether the outcome distributions differ among groups; it does not directly test a difference between arithmetic means. The record nevertheless posts means and standard deviations for each arm. Those summaries offer a description of the group results, but they do not provide the result of the specified overall test. No secondary results are posted in the registry record.

7. Results Posted in the Registry

• Normal Saline: mean 218.20 versus 165.50 on control; difference 52.70 (95% CI -11.45 to 116.85), standardized effect d = 0.40; z-test p = 0.107.
• IV Dexmedetomidine: mean 233.80 versus 165.50 on control; difference 68.30 (95% CI -0.89 to 137.49), standardized effect d = 0.48; z-test p = 0.053.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry names the Kruskal-Wallis test for the primary comparison among the three arms. It also posts arm-level means and standard deviations and includes pairwise mean differences with confidence intervals and p-values. These are different statistical summaries, and their roles should be kept distinct.

What does the Kruskal-Wallis test assess?

General statistical explanation: the Kruskal-Wallis test ranks observations across groups and evaluates evidence that the outcome distributions are not the same. It is often used when an outcome is continuous or ordinal and a comparison based directly on means is not the intended analysis. Its interpretation is about group distributions or ranks; it is not automatically a test of a difference in arithmetic means. The registry does not report the test statistic, degrees of freedom, p-value, or any post-test comparisons for the stated analysis. Therefore, its result cannot be reconstructed from the posted means and standard deviations.

General statistical explanation: rank-based tests can be useful when observations are skewed or when the assumptions of a mean-based model are questionable. They still require an appropriate design and valid outcome data, and their interpretation can be affected by differences in distribution shape. The registry does not report distribution plots, medians, or other information that would allow a fuller assessment of the outcome's shape.

What do the means and standard deviations describe?

The posted means are 165.5 for local dexmedetomidine, 218.2 for normal saline, and 233.8 for intravenous dexmedetomidine. The standard deviations are 133.0, 132.9, and 153.1, respectively. A mean describes the arithmetic average of the observed outcome values. A standard deviation describes their spread around that average. General statistical explanation: a large standard deviation relative to a mean indicates that individual observations vary considerably around the group average; it does not itself show whether the group means differ reliably.

The outcome is an area under the curve built from repeated pain scores. Thus, each participant's summary depends on a sequence of measurements, not a single score. The record says the trapezoid rule was used, a method that approximates the area by connecting successive observations with straight segments. The registry does not state the measurement schedule or how an incomplete sequence was treated, so the calculation cannot be independently assessed from the record.

How should the pairwise recalculations be read?

The pairwise estimates are unadjusted recalculations from posted summary statistics. For normal saline compared with local dexmedetomidine, the mean difference is 52.7, with a confidence interval from -11.45 to 116.8 and p = 0.107. For intravenous dexmedetomidine compared with local dexmedetomidine, the mean difference is 68.3, with an interval whose lower bound is just below zero and whose upper bound is 137.5, and p = 0.053. Each estimate is the comparison-arm mean minus the local dexmedetomidine mean. These recalculations use the means and standard deviations and are not the registry's stated Kruskal-Wallis analysis. The record does not report sponsor-generated pairwise analyses.

General statistical explanation: a confidence interval represents a range of values compatible with the data and the method used to calculate the interval. It expresses uncertainty in an estimate, rather than the range of individual participant outcomes. A p-value measures how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the test. A p-value does not give the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an observed difference.

Why can means and ranks tell different stories?

Means are sensitive to the magnitudes of observed values, especially unusually high or low values. Rank-based procedures instead use the ordering of observations. When outcome distributions are skewed or contain extreme values, the mean and rank-based comparisons can emphasize different features of the data. General statistical explanation: over-dispersion refers to variability greater than a model or analysis expects. If variability is not adequately represented, uncertainty estimates may be too narrow and tests may be poorly calibrated. The posted standard deviations indicate substantial spread, but the registry does not give enough individual-level information to assess distributional shape or over-dispersion.

The registry's comparison across all three groups and the pairwise mean recalculations should therefore not be treated as interchangeable. The former is the stated primary method; the latter offer descriptive, unadjusted contrasts based on means. Because the overall test result is not reported, and because the registry records no analyses, the primary inferential finding remains unavailable in the registry record.

10. Confidence Intervals and Precision

The confidence intervals quantify uncertainty around the pairwise mean-difference estimates. For normal saline compared with local dexmedetomidine, the estimated difference is 52.7, and the interval ranges from -11.45 to 116.8. For intravenous dexmedetomidine compared with local dexmedetomidine, the estimate is 68.3; the lower interval bound is just below zero and the upper bound is 137.5. Both intervals include zero, so the posted recalculations do not rule out no mean difference.

The intervals also allow for positive differences larger than the point estimates. This breadth indicates limited precision: the data are compatible with a range of possible differences, including values near zero and appreciably larger positive values. The point estimates alone should not be treated as exact or as a complete account of uncertainty. The p-values of 0.107 and 0.053 likewise do not replace the intervals; they summarize evidence against a null value under the assumptions of the unadjusted recalculations.

General statistical explanation: a confidence interval is not a prediction interval for individual outcomes and does not mean that most participant scores fall within its bounds. It concerns uncertainty about a group-level parameter, here a mean difference, under the method's assumptions. The recalculated intervals are unadjusted and based on summary statistics. They do not incorporate a correction for multiple comparisons and are not the result of the registry's stated Kruskal-Wallis test.

The posted standard deviations, ranging from 132.9 to 153.1, are large compared with the observed mean differences. This provides context for why estimates from the listed group sizes remain uncertain, but the standard deviations describe within-arm variation rather than uncertainty in the means themselves. The registry does not post confidence intervals for the three group means or for the overall rank-based comparison.

11. 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 estimates are planning illustrations based on the observed pairwise effects, not a record of the trial's original design calculations. For the comparison of normal saline with local dexmedetomidine, the estimates are 100 participants per arm for 80% power and 134 participants per arm for 90% power when planning for 100% of the observed effect. For the intravenous dexmedetomidine comparison, the corresponding figures are 70 and 93 participants per arm.

The estimates also consider planning for 75% and 50% of the observed effect. For the normal saline comparison, planning for 75% gives 178 participants per arm for 80% power and 238 for 90% power; planning for 50% gives 400 and 535. For the intravenous comparison, planning for 75% gives 124 and 165, while planning for 50% gives 277 and 371.

These are participants per arm, not total participants or total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect. The 80% power column means the planned design would have an 80% chance of detecting an effect of that specified size under the assumptions if the effect were present. The 90% column has the analogous interpretation for 90% power. Smaller effects need more participants to detect with the same power under these assumptions.

These figures are not observed power. They are hypothetical planning estimates derived from the observed effects and do not establish the adequacy of the completed trial's design. The trial's own sample-size assumptions and justification are not reported in the registry record.

12. 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 = 52.700; pooled standard deviation σ = 132.950.
2. n = 2 × (1.96 + 0.842)² × 132.950² / 52.700² = 99.9, rounded up to 100 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 <- 52.7                      # observed difference in means
sigma <- 132.950009402031                     # 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(971178)
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 = 100 (80% power), 134 (90% power)
 75% of observed effect: n per arm = 178 (80% power), 238 (90% power)
 50% of observed effect: n per arm = 400 (80% power), 535 (90% power)
power.t.test: 100.9 
Simulated power at n = 100 per arm: 0.793 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary comparison among three groups using the Kruskal-Wallis test. It does not report the result of that test, any follow-up comparisons, or a plan for handling multiple comparisons. The pairwise p-values discussed for the mean differences are unadjusted recalculations, so they do not account for examining more than one comparison. Without a reported multiplicity strategy, those p-values should be viewed as exploratory descriptions rather than as a complete family-wise analysis.

The record lists two outcome measures, but it does not post secondary results. No analysis results are recorded. The registry does not report whether there were prespecified secondary endpoints beyond the count of measures, or how outcomes were prioritized if several analyses were considered.

Missing-data handling is not reported in the registry record. In particular, the record does not say whether every randomized participant contributed a primary outcome, how incomplete pain-score sequences were handled when calculating the area under the curve, or whether any imputation was used. The analysis population is also not reported: the record does not identify an intention-to-treat, per-protocol, or other population for the outcome analysis.

These omissions matter because the primary outcome combines repeated measurements over time. If some measurements are absent, the area-under-the-curve calculation and the set of participants included in the analysis may depend on the handling rules. Without those rules, readers cannot determine whether missingness could have influenced the group summaries or the recalculated comparisons.

The registry also does not report an adjusted model, baseline outcome values, or covariates used in analysis. The posted pairwise estimates are unadjusted comparisons based on summary statistics. No information is given about interim analyses, stopping rules, or the original statistical analysis plan. Those details are not reported in the registry record and cannot be inferred from the posted results.

14. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 33 participants at risk for serious adverse events in each arm. It records zero serious adverse events for local dexmedetomidine, zero for normal saline, and zero for intravenous dexmedetomidine. The listed death count is zero in each arm. These are the registry's reported counts; they do not establish that no events occurred outside the record's reporting scope.

For other adverse events, the record lists 32 affected participants in the local dexmedetomidine arm, 30 in the normal saline arm, and 33 in the intravenous dexmedetomidine arm, with 33 at risk in each arm. The registry does not list the terms or types of these other events. The affected-participant counts should not be interpreted as event counts, since the record does not say whether participants could experience multiple events or how the categories were defined.

These data are descriptive and do not establish comparative safety. The record provides no event-level detail, severity breakdown, timing, attribution method, or statistical comparison. The absence of listed serious events and deaths in these groups is not evidence that risks are absent, particularly without further information on ascertainment and follow-up.

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

The posted primary outcome summaries show lower mean area-under-the-curve pain scores in the local dexmedetomidine group than in the normal saline and intravenous dexmedetomidine groups. The recalculated mean differences are positive when expressed as the comparison-arm mean minus the local-arm mean. Their confidence intervals are broad and include zero, and their unadjusted p-values are 0.107 and 0.053.

This pattern describes the observed group averages; it does not establish that local administration caused lower pain scores. The estimates are uncertain, are based on summary statistics, and do not represent the registry's stated overall Kruskal-Wallis analysis. The record does not post that test's result, so the primary inferential conclusion cannot be recovered from the record.

Nor do these results establish that the groups were equivalent. A confidence interval that includes zero can be compatible with no difference, but it may also be compatible with meaningful differences in either direction. The record does not report an equivalence or non-inferiority design, a prespecified margin, or a result assessing equivalence. Absence of clear evidence of a difference is not the same as evidence that differences are absent.

The endpoint measures pain scores summarized over the postoperative 72 hours and does not, by itself, describe every aspect of recovery, adverse events, or longer-term outcomes. The registry posts no secondary outcome results. The adverse-event record lists no serious adverse events or deaths in the arms, but other event details are not provided, and the available counts alone do not settle comparative safety.

Interpretation is further limited by unreported analysis populations, missing-data procedures, and participant characteristics. The record does not provide doses or detailed intervention procedures. Accordingly, the posted material supports a description of the recorded summaries and their uncertainty, but not a broad claim about treatment effects or how the findings apply beyond the trial setting.

16. Why This Trial Matters Statistically

This trial is statistically instructive because its registry record places a rank-based, three-group primary analysis alongside group means and pairwise mean-difference recalculations. The distinction matters: the Kruskal-Wallis test addresses differences in group distributions or ranks, whereas a mean difference describes an arithmetic-average contrast. One kind of result cannot be substituted for the other.

The group means show an ordering, with the local dexmedetomidine arm having the lowest posted mean. Yet the pairwise intervals are broad and include zero. The example illustrates why a visible difference in averages is not enough to establish a precise or reliable treatment contrast. Uncertainty needs to be read alongside the estimate, and p-values do not convey the size or practical importance of a difference.

The registry also illustrates the limits of incomplete reporting. It names the primary test but does not post its result, and it does not report the analysis population, missing-data procedures, or multiplicity plan. Because the endpoint summarizes repeated measurements, these details are important for understanding how the reported values were obtained and what participants contributed to them.

Finally, the planning illustrations show how sample-size requirements depend on the target effect under stated assumptions. Estimates based on smaller fractions of the observed effect require more participants per arm. They are planning scenarios rather than evidence about the power achieved by the completed trial. Together, these features make the record a useful case for distinguishing observed summaries, inferential analyses, and prospective planning calculations.

17. 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 follow from what the registry does not report. Participant eligibility criteria and characteristics are absent, so it is not possible to assess the makeup of the enrolled population or how closely it reflects other settings. The record identifies bilateral third molar surgery under general anaesthesia, but provides no further clinical detail about participants or procedures.

The intervention descriptions do not give doses, timing, or other administration details. The masking entry says quadruple, but does not identify who was masked or describe the masking procedures. Allocation is recorded as randomized, but the method of sequence generation and allocation concealment is not reported in the registry record.

The primary outcome depends on repeated pain scores over postoperative 72 hours. The record does not state the exact measurement schedule, completeness of follow-up, or how incomplete score sequences were handled in the area-under-the-curve calculation. It also does not identify the analysis population or any imputation approach. These omissions limit assessment of possible missing-data effects.

The registry names a Kruskal-Wallis test but does not post its result. It records no analyses and provides no analysis plan, multiplicity procedure, interim-analysis information, or sample-size justification for the original trial. The pairwise mean comparisons are unadjusted recalculations and do not supply the missing primary result. Although the record reports other adverse-event counts, it does not list event terms or provide detail on severity, timing, or attribution.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Analgesic Effect of Peripheral Dexmedetomidine — NCT00971178.
• Registry record last updated 2020-12-11; status last verified 2020-11.
• Results first posted 2020-12-11.
• 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.

21. Record Summary

NCT00971178 is a completed Phase 3 randomized, quadruple-masked, parallel trial sponsored by The University of Hong Kong. It evaluates local dexmedetomidine, normal saline, and intravenous dexmedetomidine in the setting of bilateral third molar surgery under general anaesthesia. The registry records enrollment of 105 and lists 33 participants in each arm.

The primary outcome is pain score at rest over 72 hours after surgery, expressed as an area under the curve and reported as a mean with standard deviation. The registry names the Kruskal-Wallis test for the three-group comparison but does not post its result. Unadjusted recalculated pairwise mean differences have broad intervals that include zero.

The record also lists adverse-event counts, with zero serious adverse events and zero deaths in each arm. Other event terms are not reported. Analysis populations, missing-data procedures, and the original sample-size rationale are not reported in the registry record.