The Effects of Scalp Block With Bupivacaine Versus Levobupivacaine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Scalp Block With Bupivacaine Versus Levobupivacaine (NCT02497040), a randomized phase 4 study. The primary outcome is Change in Mean Arterial Pressure.

2. Clinical Question

3. Trial Design

This was a completed, randomized, double-blind, parallel-group, Phase 4 study. The registry record lists 90 enrolled participants. Its summary describes three groups: bupivacaine, levobupivacaine, and saline placebo, with 30 participants in each group. The scalp block was performed 5 min before head pinning. The study start is recorded as 2008-03, and primary completion as 2009-03. Uludag University is listed as the sponsor.

The active treatments were 20 ml of 0.5% bupivacaine and 20 ml of 0.5% levobupivacaine; the placebo was saline. Randomization means treatment assignment was determined by chance rather than being selected solely by the treating team or participant. A parallel design means participants were assigned to a group and the groups were compared, rather than each participant receiving every study treatment in sequence. The record identifies the trial as double-blind, but does not specify which roles were masked or describe allocation concealment.

The primary outcome is listed as change in mean arterial pressure, expressed in mmHg. The registry records the timeframe as “220+-70 minutes”; it does not clarify how that notation should be interpreted. The study summary names heart rate, visual analogue scale scores, and additional intraoperative and postoperative drug use as secondary outcomes. However, secondary outcome results are not reported in the registry record. The posted results include one outcome measure and no analyses, so the available numerical comparison is limited to the reported group summaries and unadjusted contrasts.

The intervention descriptions and arm labels are not entirely straightforward: the registry includes a combined “Bupivacaine,Levobupivacaine” arm label as well as separate Levobupivacaine and Bupivacaine labels. The study summary describes three treatment groups, but the record does not fully resolve the mismatch in wording. Interpretation of the posted comparisons should therefore follow the comparison labels and their stated reference mean, without assuming additional details about treatment coding.

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

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 Change in Mean Arterial Pressure, measured over 220+-70 minutes.

The primary endpoint is titled “Change in Mean Arterial Pressure” and is expressed in mmHg. Mean arterial pressure is a continuous measure of arterial pressure over the cardiac cycle. In this trial, it was used to assess the hemodynamic response associated with head pinning after a scalp block. The registry summary identifies MAP as the primary outcome, while heart rate, pain scores, and additional drug use are described as secondary outcomes.

The record reports a mean and standard deviation for each posted arm. The reported means are 110.0 mmHg for the arm labeled “Bupivacaine,Levobupivacaine,” 105.0 mmHg for Levobupivacaine, and 100.0 mmHg for Bupivacaine; each group has a reported standard deviation of 20.0. The comparison estimates use the first of those means as the reference. Because the endpoint is called a change but the record does not describe the baseline measurement, calculation of change, or direction of subtraction, the displayed values should be interpreted as the registry's reported endpoint summaries, not as a reconstructed analysis of individual measurements.

As a general statistical point, a continuous endpoint retains information about the measured value rather than reducing it to a count of participants above or below a threshold. The mean describes the group average, while the standard deviation describes variability among observations. Neither alone shows the full distribution or the precision of a between-group contrast; the confidence intervals on the contrasts address that latter question.

7. Results Posted in the Registry

• Levobupivacaine: mean 105.00 versus 110.00 on control; difference -5.00 (95% CI -15.12 to 5.12), standardized effect d = -0.25; z-test p = 0.333.
• Bupivacaine: mean 100.00 versus 110.00 on control; difference -10.00 (95% CI -20.12 to 0.12), standardized effect d = -0.50; z-test p = 0.053.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcome is continuous, and the registry reports group means and standard deviations. The comparison estimates are unadjusted mean differences based on those group summaries. In general, a mean difference expresses the gap between two group averages in the original measurement units; a negative estimate indicates that the comparison group's mean is lower than the reference mean under the stated subtraction order. Here, the posted estimates are -5.0 mmHg for Levobupivacaine and -10.0 mmHg for Bupivacaine, each relative to the reference mean of 110.0 mmHg.

What does the standard deviation describe?

Standard deviation describes how spread out individual measurements are around their group mean. It is not the same as the standard error of a mean difference or the confidence interval. The registry reports a standard deviation of 20.0 for each arm and a pooled standard deviation of 20.0 for the comparisons. As a general statistical point, greater variability makes it harder to distinguish a group contrast from ordinary variation, while less variability can make a given contrast more precisely estimated. The standard deviation does not by itself show whether the measurements are symmetric, contain outliers, or follow a particular distribution.

What does an unadjusted comparison mean?

An unadjusted comparison uses the posted summaries to estimate a difference without accounting for other participant characteristics or covariates. This is distinct from an adjusted model that might account for baseline MAP or other factors. No adjusted model result is reported in the registry record. The record also does not report a detailed statistical analysis plan, so it is not possible to establish from the registry how the analysis was specified before the data were examined. Randomization supports a comparison of assigned groups, but it does not eliminate the importance of knowing how outcomes and analysis populations were handled.

How should the confidence interval be understood?

A confidence interval gives a range of values compatible with the data and the method's assumptions. In repeated use of a valid procedure, intervals constructed in this way would cover the fixed underlying effect at the stated rate. It is not correct to treat a particular interval as assigning a probability to the true effect after observing the data. For Levobupivacaine, the reported interval runs from -15.12 to 5.121 mmHg. For Bupivacaine, it runs from -20.12 to 0.121 mmHg. Since each interval contains zero, each is compatible with no mean difference as well as with nonzero differences in either direction.

The registry gives standard errors of 3.651 for each arm in both comparisons. A standard error describes uncertainty in an estimate, rather than variability among individual measurements. General statistical interpretation links a smaller standard error with a narrower interval when the other features of the calculation are held constant. The posted confidence intervals are more informative about uncertainty than the point estimates alone, but they do not account for possible bias from missing data, departures from the analysis plan, or selection among multiple outcomes.

What do the p-values add?

The posted unadjusted p-values are 0.333 for the Levobupivacaine comparison and 0.053 for the Bupivacaine comparison. A p-value is calculated under a null hypothesis and a statistical model; it describes how often results at least as extreme would occur if that null model held. It does not give the probability that a treatment has no effect, and it does not measure the probability that a result will replicate. The registry record does not report a multiplicity adjustment, so these p-values should not be treated as adjusted for the range of outcomes or comparisons that may have been considered.

For general context, a conventional significance threshold is sometimes used to organize hypothesis tests, but the registry does not report the trial's original threshold or testing plan. The sample-size illustration lists a two-sided significance level of 0.05; that planning assumption is not, by itself, documentation of the original trial's analysis rule. The bupivacaine p-value is close to that planning value, but the estimate and interval remain the key description of direction and precision. A near-threshold p-value does not turn an uncertain estimate into a definitive finding.

What can be inferred from the standardized effects?

The registry reports standardized differences of -0.25 for Levobupivacaine and -0.5 for Bupivacaine. A standardized effect expresses a mean difference relative to a standard deviation, allowing a scale-free comparison of magnitude. It can be useful when comparing measures expressed in different units, but it depends on the variability used for standardization and is not a substitute for the original-unit estimate. For interpretation in this study, the mmHg differences and their intervals remain central. No clinical importance threshold is reported, and no standardized-effect interval is provided.

All statistical methods described beyond the posted summaries are general explanations. The registry record does not report whether assumptions such as the distribution of values, equal variances, or handling of repeated measurements were assessed. It also does not report model diagnostics, baseline adjustment, or sensitivity analyses. These omissions limit the ability to evaluate whether the unadjusted summary comparison captures all relevant features of the study data.

10. Confidence Intervals and Precision

The Levobupivacaine mean difference is -5.0 mmHg, with a 95% confidence interval from -15.12 to 5.121 mmHg. The Bupivacaine mean difference is -10.0 mmHg, with a 95% confidence interval from -20.12 to 0.121 mmHg. These intervals describe uncertainty around the estimated group contrasts, not the range of individual participants' MAP values.

Both intervals include zero, so the posted data do not rule out a null mean difference under the calculation used. They also extend to negative values, and each extends to positive values. Thus, each estimate remains compatible with contrasts in both directions. The Bupivacaine interval reaches close to zero at its upper end, while still allowing a small positive difference; the Levobupivacaine interval extends further above zero. The exact interval limits matter: a point estimate alone would conceal this uncertainty.

As a general statistical point, a confidence interval's width reflects precision. Wider intervals indicate that a broader range of effect sizes remains compatible with the data and method; narrower intervals indicate greater precision. The intervals should not be interpreted as probability statements about the true effect, and they do not account for unreported sources of bias or analysis choices. They are based on the unadjusted comparison and the posted summaries.

The registry does not report a clinically important difference threshold for MAP. Without such a threshold, statistical uncertainty can be described, but the interval cannot be classified against a trial-defined benchmark for practical importance. The registry also does not report adjustment for multiple comparisons. The confidence intervals are therefore best read as precision summaries for the stated contrasts, rather than as a complete assessment of all uncertainty surrounding the study conclusions.

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 planning figures are participants per arm for each two-arm comparison, not total events. They are illustrations computed from the observed effect, not the trial's own design justification. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses the stated fraction of the observed effect as the effect to detect. The registry record does not report the trial's original sample-size assumptions or justification.

The 80% power column describes the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding planning number for a design with a 90% chance under the same assumptions. These are design calculations, not guarantees about a future study's result. They are not observed power: observed power is not a useful substitute for interpreting the effect estimate and its confidence interval after the trial has been completed.

For the Levobupivacaine comparison, planning for 100% of the observed effect gives 252 participants per arm for 80% power and 337 participants per arm for 90% power. Planning for 75% gives 447 participants per arm for 80% power and 598 participants per arm for 90% power. Planning for 50% gives 1,005 participants per arm for 80% power and 1,345 participants per arm for 90% power.

For the Bupivacaine comparison, planning for 100% of the observed effect gives 63 participants per arm for 80% power and 85 participants per arm for 90% power. Planning for 75% gives 112 participants per arm for 80% power and 150 participants per arm for 90% power. Planning for 50% gives 252 participants per arm for 80% power and 337 participants per arm for 90% power. In each comparison, smaller effects require more participants to detect under the same assumptions. The calculations rely on the observed effects, which are uncertain estimates, and should be treated as planning illustrations rather than evidence that the original trial was adequately or inadequately sized.

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 = -5.000; pooled standard deviation σ = 20.000.
2. n = 2 × (1.96 + 0.842)² × 20.000² / -5.000² = 251.2, rounded up to 252 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 <- -5                      # observed difference in means
sigma <- 20                     # 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(2497040)
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 = 252 (80% power), 337 (90% power)
 75% of observed effect: n per arm = 447 (80% power), 598 (90% power)
 50% of observed effect: n per arm = 1,005 (80% power), 1,345 (90% power)
power.t.test: 252.1 
Simulated power at n = 252 per arm: 0.803 (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 record reports one outcome measure and no analyses, and it does not post results for the secondary outcomes named in the study summary. Those secondary outcomes include heart rate, visual analogue scale scores, and additional intraoperative and postoperative drug use. It is not reported in the registry record whether these outcomes were measured, analyzed, or omitted from the posted results. The reason for their absence is also not reported in the registry record.

Multiplicity arises when several outcomes, time points, groups, or statistical comparisons are tested. As a general statistical point, considering many tests can increase the chance of at least one apparently unusual result even when no underlying effect exists. Methods such as a prespecified testing hierarchy or adjustment can address some multiplicity concerns, but the registry record does not report a multiplicity plan or adjustment. The posted p-values are unadjusted.

The record does not report the analysis population definition, whether participants were analyzed according to randomized assignment, or how withdrawals and protocol deviations were handled. It does not report the amount or pattern of missing outcome data, the method used to handle missing values, or sensitivity analyses. These details matter because analyses restricted to participants with observed measurements can differ from analyses that retain all randomized participants under specified assumptions.

Additional details that could clarify interpretation—including baseline outcome summaries, the prespecified analysis plan, the original sample-size justification, interim analyses, and model diagnostics—are not reported in the registry record. Their absence does not establish that these procedures were not conducted; it means the posted record does not document them. As a result, the reported unadjusted comparisons can be described, but the registry information does not support a full assessment of multiplicity control, missing-data handling, or the analysis population.

14. 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.

Most frequent non-serious adverse event terms

The adverse-event record lists 0 serious adverse events among the 30 participants at risk in the Bupivacaine,Levobupivacaine arm, 0 among the 30 at risk in the Levobupivacaine arm, and 0 among the 30 at risk in the Bupivacaine arm. The record also lists 0 other adverse events among the 30 participants at risk in each of those groups. These are the posted counts for the recorded categories.

A count of zero means no event in that category was recorded for the stated group in this registry entry. It does not establish that the risk is absent, and it cannot by itself show that the treatments have equivalent safety. When event counts are small or absent, the data may provide limited precision about uncommon harms. The registry record does not provide event descriptions because no serious-event terms are listed. Death counts are not reported in the registry record.

The safety figures should be interpreted as reported, rather than as a comprehensive assessment of every possible adverse effect. The record does not describe how adverse events were defined, how long safety follow-up lasted, or whether all events were actively collected. The study summary gives a postoperative assessment context for pain, but it does not establish the safety follow-up period. These details are not reported in the registry record.

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

The posted results show group mean MAP values of 110.0 mmHg for the reference arm, 105.0 mmHg for Levobupivacaine, and 100.0 mmHg for Bupivacaine. The corresponding unadjusted mean differences are -5.0 mmHg and -10.0 mmHg. Their confidence intervals include zero, and the p-values are 0.333 and 0.053. In statistical terms, the estimates are uncertain and do not establish a clear difference from the reference group on the reported primary outcome.

This does not demonstrate that the groups are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether the plausible difference lies within that margin; no such margin or equivalence analysis is reported in the registry record. Nor do these results prove that there is no effect. The intervals allow a range of possible contrasts, and the record does not report a clinical threshold for judging the importance of those values.

The outcome is described as change in MAP, but details of the measurement and calculation are absent from the registry entry. The recorded timeframe is “220+-70 minutes,” and its meaning is not clarified. The arm labels also do not align cleanly with all of the treatment descriptions. These reporting limits make it important to interpret the numerical results as posted, without inferring unreported measurement or analysis details.

The registry summary names secondary outcomes, but their results are not reported in the registry record. Therefore, the primary MAP summaries cannot answer questions about heart rate, pain scores, or additional medication use. Similarly, the adverse-event counts document zero recorded events in the listed categories, but do not establish absence of risk. The most defensible conclusion is limited to the posted group summaries and their unadjusted precision; broader conclusions about all trial outcomes or clinical consequences are not supported by the registry information alone.

16. Why This Trial Matters Statistically

This study illustrates why a clinical trial result should be read through both its point estimate and its uncertainty. The means and estimated contrasts provide a direction and scale for the observed differences, while confidence intervals show that the data remain compatible with a range of values. Reporting a p-value without the interval would obscure how much uncertainty remains; reporting only the means would not directly quantify the between-group contrast.

It also highlights the difference between statistical evidence and clinical importance. The record does not state a threshold for a meaningful change in MAP, so the estimates cannot be judged against a trial-defined clinical benchmark. A result that is statistically uncertain is not automatically unimportant, just as a numerical difference is not automatically important. The outcome context and a prespecified threshold would be needed to make that distinction responsibly.

The registry's sample-size illustrations reinforce another statistical point: the number of participants needed depends on the effect a study is designed to detect. The planning figures rise as the target effect becomes smaller. These are illustrations based on the observed effects, not evidence about the trial's original rationale or its achieved power. Treating them as retrospective proof of adequacy would confuse planning with inference.

Finally, the record demonstrates the importance of complete reporting. Secondary outcomes, analysis-population details, missing-data methods, multiplicity handling, and the original design assumptions are not reported in the registry record. Such information helps readers understand what was measured, how many questions were tested, and how robust the findings may be. The available results remain interpretable as posted summaries, but their limits should remain visible alongside the numerical comparisons.

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.

The primary endpoint is labeled as a change in MAP, but the registry does not describe the baseline value, measurement schedule, calculation of change, or direction of subtraction. Its timeframe is recorded as “220+-70 minutes,” without an explanation of the notation. This limits reconstruction of exactly what the posted means represent.

Arm naming is also unclear. The results include an arm labeled “Bupivacaine,Levobupivacaine,” while the summary describes separate bupivacaine, levobupivacaine, and saline groups. The accompanying arm descriptions do not clearly resolve all treatment-to-label mappings. This makes careful reading of the named comparisons important; the record does not provide enough detail to independently reconstruct the full allocation and coding.

The posted analysis is limited to group summaries and unadjusted mean differences. The registry record does not report baseline MAP, covariate adjustment, model diagnostics, missing-data handling, or a defined analysis population. Secondary results are not reported in the registry record despite the summary naming several secondary outcomes. The original sample-size justification, analysis plan, interim analyses, and multiplicity procedures are also not reported in the registry record.

Finally, the safety information is limited to the recorded adverse-event counts and does not describe event definitions or follow-up duration. The record lists no serious or other adverse events in the groups, but does not report deaths. These reporting limits prevent a detailed assessment of safety precision or completeness. They do not establish that unreported methods or assessments were not conducted; they indicate that those details cannot be evaluated from the registry entry.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: The Effects of Scalp Block With Bupivacaine Versus Levobupivacaine — NCT02497040.
• Registry record last updated 2018-01-05; status last verified 2017-12.
• Results first posted 2018-01-05.
• 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.

21. Record Summary

The registry record describes a completed, randomized, double-blind, parallel-group Phase 4 study sponsored by Uludag University. It lists 90 enrolled participants and compares scalp blocks using bupivacaine or levobupivacaine with saline placebo. The study summary describes the block as being performed 5 min before head pinning in patients classified as ASA Physical Status I-II.

The primary posted outcome is change in mean arterial pressure in mmHg. The group means are 110.0, 105.0, and 100.0, with a standard deviation of 20.0 in each group. The unadjusted mean differences versus the reference mean are -5.0 mmHg for Levobupivacaine and -10.0 mmHg for Bupivacaine; both confidence intervals include zero.

Secondary outcome results, the original sample-size justification, missing-data procedures, analysis-population details, and multiplicity methods are not reported in the registry record. The adverse-event counts list zero serious and zero other events in each group; deaths are not reported in the registry record.