Determination of the Duration of Action of a Lidocaine and a Bupivacaine Digital Nerve Block in Human Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Determination of the Duration of Action of a Lidocaine and a Bupivacaine Digital Nerve Block in Human Volunteers (NCT01508832), a randomized phase 4 study. The primary outcome is The Change in the Average Finger Temperature From Baseline to Post-intervention..

2. Clinical Question

The practical statistical focus is the contrast in the primary endpoint, not a direct measurement of how long a block lasted. The posted results give a mean change for each treatment and a mean difference with a confidence interval and p-value. Those summaries describe the observed temperature outcome in this small volunteer study. They do not establish how temperature change corresponds to sensory or sympathetic block duration, nor do they answer questions about other outcomes that were not posted. The study's crossover designation means participants were assigned treatments in a crossover framework, but details needed to assess treatment order, period effects, or within-person analysis are not reported in the registry record.

3. Trial Design

The registry lists this as a completed phase 4 study sponsored by the University of California, San Francisco. It enrolled 12 participants and is described as randomized, double-masked, and crossover. The interventions were a lidocaine digital nerve block and a bupivacaine digital block. The arm descriptions specify lidocaine 1% in a volume of 2 cc and bupivacaine 0.25% in a volume of 2 cc.

The crossover designation indicates that the trial was not registered simply as a conventional parallel-group comparison. However, the registry record does not report the treatment sequence, how randomization was implemented, whether a washout period was used, or how measurements from different treatment periods were handled. It also does not describe who was masked or how masking was maintained. These omissions prevent a more detailed assessment of the design from the registry information alone.

The primary outcome is described as the change in average finger temperature from baseline to post-intervention, in degrees centigrade. Its timeframe is listed as 30 minutes prior and 240 minutes post intervention. The endpoint description states that the correspondingly treated finger of all 12 study participants was included in the analysis for each arm or group. The posted results list 12 participants for lidocaine and 12 for bupivacaine. Those arm-level counts should be read alongside the crossover design; they do not establish that there were 24 distinct participants.

The registry reports one outcome measure and no posted analyses. It lists no posted secondary outcomes. The study's brief summary describes hypotheses about the relative durations of autonomic, sensory, and perfusion-index changes, but there are no corresponding posted results. The registry's original sample-size justification, analysis plan, treatment-period procedures, and approach to missing measurements are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Analysis population for the primary outcome, as defined in the registry: The correspondingly-treated(lidocaine, bupivacaine) finger of all 12 study participants included in analysis for each arm/group

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 The Change in the Average Finger Temperature From Baseline to Post-intervention., measured over 30 minutes prior and 240 minutes post intervention..

The primary endpoint is the change in average finger temperature from baseline to post-intervention, measured in degrees centigrade. The registry gives a timeframe of 30 minutes prior and 240 minutes post intervention. It reports a mean for each treatment group and a standard error as the measure of spread. The endpoint description identifies the correspondingly treated finger of all 12 study participants as the analysis population for each arm or group.

Finger temperature is the outcome used for the posted comparison; the registry does not describe it as a direct measure of sensory block duration or sympathetic block duration. The study's brief summary proposes expectations about how long autonomic and sensory block, and increased perfusion index, would last. Those proposed outcomes are distinct from the one posted primary measure. No outcome results for block duration or perfusion index are reported in the registry record.

Baseline-to-post-intervention change provides a way to describe how the measured temperature differs from its baseline level after treatment. The mean summarizes the average change in the analyzed observations, while the standard error describes uncertainty in that estimated mean. The comparison between treatments is summarized separately as a mean difference. Interpreting this endpoint requires keeping its measurement and timeframe in view: the posted result concerns average temperature change over the stated observation period, not every individual temperature reading, the duration of a block, or a clinical outcome beyond the measured variable.

The registry does not provide further operational details about how temperature was measured, how baseline values were formed, or how observations across the post-intervention period were condensed into the reported change. Those measurement and analysis details are not reported in the registry record.

7. Results Posted in the Registry

• Bupivacaine: mean 0.93 versus -1.35 on control; difference 2.28 (95% CI 0.31 to 4.25), standardized effect d = 0.93; z-test p = 0.023.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a mean change in finger temperature, expressed in degrees centigrade. A mean describes the average value in the observations being summarized. Here, the registry posts separate mean changes for lidocaine and bupivacaine, together with standard errors. A standard error describes the estimated uncertainty in a sample mean; it is not the spread of individual participants' measurements. Individual-level variation would ordinarily be described with a standard deviation or another distributional summary, but the registry's primary results list standard errors.

The treatment comparison is reported as a mean difference. In this record, the comparison is bupivacaine relative to lidocaine, with a posted estimate of 2.28 degrees centigrade. The two arm means are -1.35 and 0.93 degrees centigrade, respectively. The sign and direction of a mean difference depend on which treatment is subtracted from which, so the comparison label matters. The record's estimate expresses the contrast in the outcome's original units, which makes it possible to interpret the size and direction without converting it to another scale.

A confidence interval communicates uncertainty around an estimated quantity. In general, a 95% confidence interval is generated by a method designed to produce intervals that contain the underlying parameter in 95% of repeated applications under the method's assumptions. It is not a statement that there is a 95% probability that this particular interval contains the true value. Here, the interval for the mean difference runs from 0.312 to 4.248 degrees centigrade. Its width reflects uncertainty in the estimated contrast, and the interval should be read together with the study's small participant count and the limitations in the registry's description of analysis methods.

The p-value is another summary of statistical evidence, but it answers a different question from the confidence interval. In general, a p-value measures how compatible the observed result, or a more extreme result, is with a specified null model, assuming the model and analysis assumptions hold. The posted unadjusted p-value is 0.023. It is not the probability that the null hypothesis is true, the chance that the result is wrong, or a measure of effect size. The registry does not report the exact test, degrees of freedom, or a full analysis specification, so those details cannot be independently assessed from the posted record.

The study is identified as randomized, double-masked, and crossover. In a crossover design, participants can receive more than one intervention, allowing comparisons to draw on observations from the same participant. This structure can be statistically useful because a participant can serve as their own reference, but it also makes the handling of repeated observations important. The treatment sequence, period structure, washout, and any assessment of carryover are not reported in the registry record. Nor does the record explain whether the posted mean difference was estimated using paired observations or another model. No particular analysis method should be inferred from the crossover label alone.

General statistical principle: when data are more variable than a model expects, or observations are correlated in ways the model does not account for, uncertainty estimates can be inaccurate. In crossover data, within-participant correlation is one reason the analysis approach matters. In other settings, over-dispersion means that observed variability exceeds the variability assumed by a model, which can make standard errors too small if ignored. The registry does not report an over-dispersion assessment, and there is no basis to claim that over-dispersion was present or relevant to the posted analysis.

The posted standard errors for the treatment means are 0.71 degrees centigrade for each group. The comparison also includes a pooled standard deviation of 2.46 and a standardized effect size of 0.927. A standardized effect expresses a difference relative to a measure of variability rather than in the original temperature units. Such summaries can help compare scales, but their interpretation depends on how the pooled variability was obtained. The record does not give details of that calculation, and the crossover structure cautions against treating summaries as if the observations necessarily came from independent groups.

The registry reports an unadjusted p-value and no posted analyses. It does not describe whether the reported comparison was prespecified in a full statistical analysis plan, whether covariates were used, or how any missing measurements were handled. Consequently, it is possible to explain the meanings of the posted summaries, but not to reconstruct the analysis or verify its assumptions from the registry record. The numerical results should be presented as registry-reported estimates rather than as an independent reanalysis.

The planning illustration uses the observed effect as a reference and asks what sample sizes would correspond to detecting specified fractions of that effect under stated assumptions. These are hypothetical design calculations, not a measure of the probability that this completed study detected an effect. They do not replace an original sample-size justification, which is not reported in the registry record. The illustration's assumptions are described in the sample-size section and should be kept separate from the trial's actual design decisions.

All explanations of confidence intervals, p-values, means, standard errors, crossover analysis, and model assumptions in this discussion are general statistical explanations. The registry's actual analytic procedures beyond the posted summaries are not reported in the registry record.

10. Confidence Intervals and Precision

The reported mean difference for bupivacaine relative to lidocaine is 2.28 degrees centigrade. Its 95% confidence interval extends from 0.312 to 4.248 degrees centigrade. The interval represents uncertainty about the estimated contrast under the analysis used. It includes a range of positive values, so the exact size of the difference remains uncertain even though the point estimate is a single number.

In general, a confidence interval is more informative than a point estimate alone because it displays both the estimated direction and a range of values compatible with the data and method. It is not a guarantee that the true value lies within the interval, nor does it capture every source of uncertainty. In particular, it does not account for limitations that may arise from unreported design details, measurement procedures, missing data, or analysis choices.

The posted endpoint results include 12 participants for each treatment group, while the design is registered as crossover. The registry does not explain the treatment-period analysis or how repeated observations were incorporated into the comparison. The interval should therefore be interpreted as the interval attached to the posted estimate, not as independent confirmation of a particular modeling approach. No alternative or adjusted confidence interval is reported in the registry record.

The confidence interval also concerns the temperature-change contrast only. It does not quantify uncertainty about the proposed duration of sensory or sympathetic block, because those outcomes are not posted. The registry does not state what range of temperature change would be meaningful, so the interval alone cannot settle the practical importance of the finding.

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 table and curve are planning illustrations based on fractions of the observed effect. The figures are participants per arm, not total events. This is a continuous outcome, and the table uses an equal allocation between the two arms. Its stated assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect to detect equal to the listed fraction of the observed effect. The trial's own original design assumptions and sample-size justification are not reported in the registry record.

The column for 80% power shows the number of participants per arm used in the illustration to give an 80% chance of detecting the specified effect under the planning assumptions, if that effect and those assumptions were correct. The 90% power column uses a higher target chance of detection under the same type of assumptions. These are planning quantities rather than descriptions of the completed trial's achieved performance.

The rows represent planning for 100%, 75%, and 50% of the observed effect. As the effect being targeted becomes smaller, the illustration requires more participants per arm. The table and curve help show how planning depends on the assumed effect size: estimates based on a large observed effect can yield smaller illustrative sample sizes than plans targeting a more modest effect.

These values are not observed power. They are prospective illustrations computed from the observed effect, not evidence about the probability that this trial's result was detected or replicated. They also do not establish what sample size the investigators chose originally; that rationale is 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 = 2.280; pooled standard deviation σ = 2.460.
2. n = 2 × (1.96 + 0.842)² × 2.460² / 2.280² = 18.3, rounded up to 19 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 <- 2.28                      # observed difference in means
sigma <- 2.45951214674781                     # 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(1508832)
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 = 19 (80% power), 25 (90% power)
 75% of observed effect: n per arm = 33 (80% power), 44 (90% power)
 50% of observed effect: n per arm = 74 (80% power), 98 (90% power)
power.t.test: 19.3 
Simulated power at n = 19 per arm: 0.791 (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 lists one outcome measure and no posted analyses. It reports the mean change in average finger temperature as the primary endpoint, but provides no posted secondary outcome results. The study summary describes expectations about the duration of autonomic and sensory block and increased perfusion index; the registry does not include results for those measures. The existence of hypotheses in the summary should not be mistaken for posted statistical tests.

The reported p-value is unadjusted. The registry record does not report a multiplicity plan, a hierarchy of outcomes, or whether additional analyses were conducted. It is therefore not possible to determine from the record whether the displayed result was one of several planned comparisons or whether any adjustment was considered. This matters because multiple statistical tests can change how a single unadjusted p-value should be interpreted.

The endpoint description says that all 12 participants were included in analysis for each arm or group, and the posted arm summaries each list 12. This is the reported analysis population for the primary endpoint. However, the record does not detail the number of measurements available at each time, whether any observations were missing, how incomplete records were handled, or whether all enrolled participants contributed data under the same analysis rule. Missing-data methods are not reported in the registry record.

The registry identifies a randomized, double-masked crossover design but does not describe the analysis population in terms such as intention-to-treat or per-protocol, and it does not explain the handling of treatment sequence, period effects, or carryover. Those features are important to understanding which observations contribute to a crossover comparison. No additional analysis population or sensitivity analysis is reported. The available record supports describing the posted endpoint summaries, but not a fuller account of multiplicity, missingness, or analytic-set decisions.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summary lists 12 participants at risk for serious adverse events in each treatment group and zero participants with a serious adverse event attributed to each group. No serious adverse-event terms are listed. These are the posted serious-event figures; they do not show that the risk of serious events is absent or that uncommon events can be excluded.

The record also lists one participant with an other, non-serious adverse event in each group, among 12 participants at risk in each. The event terms are not included in the posted summary, so its nature, timing, severity, and relationship to treatment cannot be described from this record. The registry's adverse-event fields do not provide further detail.

Deaths are not reported in the registry record. The safety summary should be read as a report of the counts recorded for this small study, not as a comprehensive estimate of safety. It does not support comparisons of safety rates or conclusions about rare outcomes. The trial is described as involving human volunteers, and the posted information does not provide broader safety follow-up details.

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

The posted results show that the average finger-temperature change differed between the two treatment groups in the registry's primary endpoint analysis. The mean change was -1.35 degrees centigrade for lidocaine and 0.93 degrees centigrade for bupivacaine. The reported mean difference for bupivacaine relative to lidocaine was 2.28 degrees centigrade, with a 95% confidence interval from 0.312 to 4.248 degrees centigrade and an unadjusted p-value of 0.023.

This is evidence about the measured temperature-change outcome in this study. It is not a direct result about the duration of sensory block, the duration of sympathetic block, or the duration of increased perfusion index. Although those ideas appear in the study summary, corresponding outcome results are not reported in the registry record. The temperature finding should not be substituted for results on those other proposed outcomes.

The result also does not, by itself, establish whether the observed contrast is practically important. The registry does not provide a threshold for a meaningful change in temperature or explain how temperature change relates to a meaningful clinical or physiological outcome. No medical advice or treatment recommendation follows from this statistical summary.

The study enrolled 12 participants and is registered as a crossover trial. The arm-level counts and comparison should be understood in that design context, while recognizing that treatment order and analysis details are not reported. The confidence interval conveys uncertainty under the posted analysis, but it cannot address every limitation in the study record. The data are best read as a small-study estimate of a specific continuous endpoint, not as a broad conclusion about treatment effects or safety.

The registry reports no secondary outcome results and no posted analyses beyond the primary result. Its record does not establish whether other planned analyses were conducted or how they might compare. A careful interpretation therefore remains limited to the posted means, contrast, interval, and p-value, along with the stated participant count and design.

16. Why This Trial Matters Statistically

This trial illustrates how a clinical registry can present a result that is statistically interpretable while leaving important analytic details unresolved. The record supplies a continuous endpoint, group means, standard errors, a mean difference, a confidence interval, and an unadjusted p-value. Together, these allow readers to describe the direction and uncertainty of the posted comparison without relying on a p-value alone.

The crossover designation makes the relationship between design and analysis especially visible. In general, crossover studies can make use of within-participant comparisons, but their interpretation depends on treatment sequence, period, and repeated-measure handling. Those details are not reported in the registry record. The case therefore shows why the design label alone cannot establish what statistical model was used or whether the posted uncertainty correctly reflects the data structure.

The trial also demonstrates why a registered hypothesis and a posted result are not the same thing. The summary describes expectations about block duration and perfusion index, yet the posted outcome is temperature change. Statistical conclusions should follow the endpoint for which results are actually reported, rather than extending a result to unreported measures.

Finally, the planning illustration helps distinguish a sample-size calculation from evidence about a completed study. Its figures depend on explicit assumptions and fractions of the observed effect, while the original design justification is not reported. This distinction is important for interpreting retrospective planning displays: they may show how assumed effect size affects sample size, but they do not describe observed power or replace the study's original rationale.

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 registry record leaves several trial-specific uncertainties. Although the study is identified as randomized, double-masked, and crossover, it does not describe the randomization procedure, treatment order, masking roles, or any washout period. It also does not explain whether the treatment comparison accounts for period or carryover effects, or how observations from the same participant were modeled. These gaps limit independent assessment of the reported confidence interval and p-value.

The primary endpoint is described as average finger-temperature change, but the record does not explain the measurement procedure, how the baseline was determined, or how the period from 30 minutes prior to 240 minutes post intervention was summarized into one change value. The registry reports standard errors for the arm means but does not provide participant-level data or a fuller distributional description.

The study enrolled 12 participants. The endpoint description says all 12 were included in each arm or group, but the record does not detail missing measurements or completeness at each time point. The analysis population terminology and the handling of incomplete observations are not reported in the registry record.

Only one outcome measure is listed, with no posted analyses and no posted secondary outcomes. The registry does not provide a full analysis plan, multiplicity procedures, the original sample-size justification, or further safety-event descriptions. The brief summary's hypotheses about block duration and perfusion index are not accompanied by results. These limitations mean the record supports a narrow account of the posted temperature result rather than a comprehensive evaluation of all study aims.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Determination of the Duration of Action of a Lidocaine and a Bupivacaine Digital Nerve Block in Human Volunteers — NCT01508832.
• Registry record last updated 2020-01-30; status last verified 2020-01.
• Results first posted 2013-08-19.
• 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 describes a completed, randomized, double-masked crossover study of lidocaine and bupivacaine digital nerve blocks in human volunteers. Enrollment was 12. The interventions are described as lidocaine 1% in a volume of 2 cc and bupivacaine 0.25% in a volume of 2 cc.

The single posted primary outcome is change in average finger temperature from baseline to post-intervention, measured in degrees centigrade. The reported mean changes were -1.35 for lidocaine and 0.93 for bupivacaine. The mean difference for bupivacaine relative to lidocaine was 2.28, with a 95% confidence interval from 0.312 to 4.248 and an unadjusted p-value of 0.023.

The registry reports no posted analyses or secondary outcome results. It records zero serious adverse events in each group and one other adverse event in each group; the event terms are not reported. Important details of the crossover procedures, analysis plan, missing-data handling, and original sample-size justification are not reported in the registry record.