Pain Control in Colorectal Surgery: Liposomal Bupivacaine Block Versus Intravenous Lidociane: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pain Control in Colorectal Surgery: Liposomal Bupivacaine Block Versus Intravenous Lidociane (NCT04005859), a randomized phase 4 study. The primary outcome is Verbal Pain Scale (VRS) - 4 Week Post-op.

2. Clinical Question

3. Trial Design

The registry identifies NCT04005859 as a completed phase 4, randomized, single-masked, parallel-group trial sponsored by Wake Forest University Health Sciences. The listed enrollment is 61. The registry start date is 2018-02-22, and the primary completion date is 2019-05-09. The condition is listed as colorectal disorders.

The parallel arms compared intravenous lidocaine with a TAP block using liposomal bupivacaine, identified as Exparel. The IV lidocaine arm is described as receiving the drug before and after surgery. The Exparel arm is described as receiving an injection for a TAP block before surgery. Which individuals were masked is not reported in the registry record, nor are details of the randomization procedure or allocation concealment.

The registry summary describes an aim to compare analgesic impact in colorectal surgery and mentions integration with an ERAS protocol. It names pain scores and morphine equivalents as primary endpoints in the summary, while the posted outcome record identifies the 4-week postoperative verbal pain scale as the primary outcome with results. These descriptions are not identical. The registry record does not explain the relationship between the summary's endpoint description and the outcome result posted for the 4-week score.

The summary also lists potential secondary outcomes, including ambulation, bowel function, diet tolerance, postoperative nausea and vomiting, length of stay, morbidity, cost, and quality of life. No secondary outcomes are posted in the results record. Further details about the protocol, treatment delivery, follow-up procedures, trial-specific sample-size justification, and analysis plan 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

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 Verbal Pain Scale (VRS) - 4 Week Post-op, measured over Single VRS assessed at 4-week post-op visit (or phone call).

The posted primary outcome is the verbal pain scale score at the 4-week postoperative visit or phone call. The measure is described as a score from 0 to 10, where 0 represents no pain and 10 represents the worst possible pain. The record describes a single assessment at that follow-up point, rather than a summary of pain across the entire postoperative period.

Pain scores capture a patient-reported experience that may not be represented by other outcomes, such as medication use or hospital stay. The registry summary describes postoperative pain and morphine equivalents as intended primary endpoints, but the result record reports a mean for the 4-week verbal pain score. The relationship between these differing descriptions is not reported in the registry record.

The posted outcome is treated as continuous and summarized using a mean and standard deviation. A mean gives a central summary of the scores in an arm, while the standard deviation describes variation among scores around that mean. These summaries do not reveal the full score distribution, each participant's experience, or how pain changed over time. The record gives no results for pain at other time points, and no results for morphine equivalents or the secondary outcomes named in the registry summary.

7. Results Posted in the Registry

• EXPERIMENTAL: Exparel: mean 1.10 versus 0.40 on control; difference 0.70 (95% CI -0.13 to 1.53), standardized effect d = 0.48; z-test p = 0.097.

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a continuous score, and the record summarizes each arm using a mean and standard deviation. The comparison is expressed as a mean difference between the Exparel arm and the IV lidocaine arm. Because the reported estimate is positive, the posted means place the Exparel score above the IV lidocaine score at the measured follow-up. The score direction indicates amount of pain, but the registry does not specify what size of difference would be important to patients or clinicians.

What does the mean describe?

A mean is the arithmetic average of the observations in an arm. It provides a compact description of the group's central score, but it does not say that every participant had that score. The observed means are 0.4 for IV lidocaine and 1.1 for Exparel. The standard deviations are 0.7 and 2.0, respectively. A standard deviation describes spread around an arm's mean; it is not a confidence interval and does not show the uncertainty in the mean difference by itself.

With a bounded pain scale, scores can occupy only the stated scale range. A mean and standard deviation do not reveal whether scores cluster at particular values, whether the distributions are skewed, or whether there are many zero scores. The registry record does not provide individual-level scores, a distributional summary, or further descriptive statistics. Such information could help readers understand the degree to which the means represent the observed score patterns.

How should the mean difference be read?

The posted contrast is the mean score in the Exparel arm compared with the mean score in the IV lidocaine arm. Its estimate is 0.7 points. This estimate describes the observed difference between arm averages, not a change from baseline: no baseline pain result is posted for this endpoint. It also does not report an individual participant's change or the proportion of participants with a particular score.

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. For a difference in means, an interval that includes zero does not rule out no difference in the underlying means at the confidence level used. The posted interval runs from -0.126 to 1.526, so it contains zero and covers possibilities on either side. The confidence level and the exact method used to calculate this interval are not reported in the registry record.

What does the p-value add?

The registry posts an unadjusted p-value of 0.097. In general, a p-value describes how compatible data are with a specified null model, given the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The test used, its assumptions, and whether this was the prespecified primary analysis are not reported in the registry record. The p-value should therefore be considered alongside the estimated difference and its confidence interval, rather than treated as a standalone conclusion.

The registry calls the trial randomized, which describes how assignment was made in the study design. Randomization can support a fair comparison by reducing systematic differences between arms in expectation, but it does not ensure that all characteristics are balanced in a particular trial. The registry does not post baseline characteristics, details of the sequence generation, or information about allocation concealment. The single-masked designation does not identify who was masked.

Why can variation matter?

General statistical interpretation: when scores vary substantially among participants, an arm mean is less informative about any one participant's score, and the estimate of the difference may be less precise. The Exparel arm has a larger posted standard deviation than the IV lidocaine arm. The confidence interval conveys uncertainty for the contrast, while the standard deviations describe observed within-arm variability. These statistics answer related but different questions.

For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes; accounting for it can affect uncertainty estimates. That concept does not directly describe this continuous pain-score result, and the registry does not report a model for count outcomes. The record also does not report a statistical analysis plan, any adjusted analyses, or the handling of repeated measurements. No conclusions about those methods can be drawn from the posted primary result alone.

10. Confidence Intervals and Precision

The mean difference is 0.7 points, with a confidence interval from -0.126 to 1.526. The interval is a measure of uncertainty about the estimated difference, not a range containing most individual pain scores. It includes zero and extends both below and above it. Accordingly, the observed positive difference does not by itself establish that the underlying difference is positive, and the interval also permits a range of positive differences.

In general, a confidence interval is constructed by a statistical method that combines an estimate with its uncertainty under specified assumptions. Its interpretation depends on the confidence level and method used. Neither is reported in the registry record. The interval's limits are therefore best read as the posted uncertainty summary rather than as a guarantee about the true difference.

The posted standard deviations, 0.7 for IV lidocaine and 2.0 for Exparel, describe dispersion among observed scores in each arm. They are not estimates of the confidence interval's endpoints. The primary outcome counts are 28 in the IV lidocaine arm and 25 in the Exparel arm. The record does not explain how the analysis handled missing scores, whether all randomized participants were included, or whether any adjustment was made. Such details affect how the estimate and its precision should be interpreted.

The result is thus more informative about the range of differences compatible with the posted analysis than about a single definitive value. There is no clinical importance threshold reported against which to judge the interval, and no additional primary-outcome time points are posted. The registry record does not report whether the interval was prespecified or whether it accounts for any analysis features beyond the two-arm 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 planning figures are participants per arm, not total event counts. They are illustrations based on the observed mean difference, not the trial's own original design assumptions. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect.

For planning at 100% of the observed effect, the figures are 69 participants per arm for 80% power and 92 participants per arm for 90% power. At 75% of the observed effect, they are 122 participants per arm for 80% power and 164 participants per arm for 90% power. At 50% of the observed effect, they are 275 participants per arm for 80% power and 368 participants per arm for 90% power.

In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting the specified effect at the chosen significance level if that effect were the true one. The 90% column describes the corresponding design with a 90% chance under those assumptions. These are planning concepts, not guarantees for an individual study. Smaller effects need more participants to detect under otherwise unchanged assumptions, which is why the planning figures rise as the target fraction of the observed effect gets smaller.

These figures are not observed power. They are planning illustrations, and the registry's original sample-size rationale and design assumptions are not reported in the registry record. The planning calculation does not establish that the trial was designed around the observed estimate or that its assumptions match the trial's actual analysis.

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 = 0.700; pooled standard deviation σ = 1.463.
2. n = 2 × (1.96 + 0.842)² × 1.463² / 0.700² = 68.6, rounded up to 69 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 <- 0.7                      # observed difference in means
sigma <- 1.46347692359065                     # 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(4005859)
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 = 69 (80% power), 92 (90% power)
 75% of observed effect: n per arm = 122 (80% power), 164 (90% power)
 50% of observed effect: n per arm = 275 (80% power), 368 (90% power)
power.t.test: 69.6 
Simulated power at n = 69 per arm: 0.794 (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

Multiplicity arises when a study tests multiple outcomes, time points, or contrasts. In general, conducting many tests can increase the chance of at least one apparently notable result, so an analysis plan may specify a primary outcome and approaches to interpreting additional tests. The registry summary lists several outcomes, including pain, morphine equivalents, recovery measures, morbidity, cost, and quality of life. The posted results record contains one outcome measure and no posted secondary outcomes.

The record does not report whether the trial specified a hierarchy of outcomes, whether multiplicity adjustment was planned, or how multiple time points or comparisons were handled. The unadjusted p-value for the 4-week score should not be taken to answer questions about an unreported multiplicity strategy. The registry record also does not clarify why the summary describes multiple primary endpoints while the outcome results identify the 4-week verbal pain score as the primary measure.

Missing-data handling is also not reported in the registry record. The outcome results list 28 participants in the IV lidocaine arm and 25 in the Exparel arm, while the registry lists enrollment of 61. The record does not explain the relationship between enrollment and the outcome counts, identify missing scores, give reasons for missingness, or describe any imputation or sensitivity analysis. It also does not state whether the posted analysis followed intention-to-treat, per-protocol, or another population definition.

These omissions matter because analytic decisions can affect both the estimated difference and its uncertainty. Without the prespecified analysis plan and details of outcome availability, readers cannot determine whether the posted analysis includes all randomized participants or whether results could differ under other reasonable missing-data assumptions. No conclusion about those possibilities can be drawn from the registry record alone.

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.

The registry reports serious adverse event counts of 0 among 28 at risk in the IV lidocaine arm and 0 among 25 at risk in the Exparel arm. It also reports other adverse event counts of 0 among 28 at risk in the IV lidocaine arm and 0 among 25 at risk in the Exparel arm. Deaths are listed as 0 in both arms.

These figures describe events recorded in the registry, not proof that no adverse events occurred outside the record's reporting definitions or observation period. The registry does not provide serious-event terms, and no serious-event terms are listed. It does not describe the adverse-event collection procedures, the duration of safety follow-up, or how events were judged related to treatment. The figures should be read as the posted safety counts with their stated at-risk denominators, not as a complete account of all possible harms.

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

The posted result describes a difference in average verbal pain scores at a specific follow-up assessment. The mean was 0.4 in the IV lidocaine arm and 1.1 in the Exparel arm, with a reported mean difference of 0.7 points. The confidence interval ranges from -0.126 to 1.526, and the unadjusted p-value is 0.097. The interval includes zero, so the registry result leaves uncertainty about the direction and size of the underlying difference.

This is not a result about all postoperative pain. It concerns a single assessment at the 4-week postoperative visit or phone call, and the record does not give results for pain at other time points. Nor is it a result about medication use: although the registry summary names morphine equivalents as an endpoint, no such result is posted. The summary's other named outcomes also have no results posted in the record.

The estimate does not establish that either intervention is better or worse. The registry does not report a threshold for a clinically important difference, so statistical uncertainty cannot be translated into a judgment about practical importance. The study's results also cannot be used to infer whether an individual will have a particular pain score.

Interpretation is further limited by absent information about the trial's original sample-size rationale, statistical analysis plan, missing outcome data, analysis population, and the masking details. The discrepancy between the summary's description of primary endpoints and the specific posted outcome result is not explained. These limitations do not change the reported numbers, but they restrict what can be concluded from them. The appropriate reading is a posted estimate with meaningful uncertainty, not a definitive answer about comparative effects.

16. Why This Trial Matters Statistically

This trial is a useful setting for distinguishing a point estimate from the strength of evidence about that estimate. The observed mean difference is 0.7 points, but the confidence interval extends from -0.126 to 1.526 and includes zero. Readers can see both the direction of the observed contrast and the uncertainty around it without treating the point estimate as a settled finding.

The outcome also illustrates why summaries should be read together. The arm means describe average scores, the standard deviations describe observed spread, and the confidence interval describes uncertainty in the comparison. These measures are related but not interchangeable. In particular, the standard deviation of scores is not the precision of the mean difference.

Another statistical issue is alignment between a registry summary and posted results. The summary names pain and morphine equivalents as primary endpoints, while the result record posts the 4-week pain score. No explanation of that difference is reported. For researchers and clinical readers, clear alignment between prespecified outcomes and results is important for understanding which questions the available analysis addresses.

The result also shows the limits of interpreting a single outcome in isolation. Secondary results are not posted, and details of missing data, multiplicity, and analysis populations are not reported. Those gaps prevent a complete appraisal of the trial's broader analysis. The registry result remains informative as an estimate for the stated follow-up measure, but it is not a complete statistical account of every outcome described in the study summary.

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 details unclear. It identifies the study as randomized and single-masked, but does not report who was masked, how the randomization sequence was generated, or whether allocation was concealed. Baseline characteristics are not posted, so the observed similarity of the arms on measured characteristics cannot be assessed from this record.

The registry lists enrollment of 61, while the primary outcome results list 28 participants in the IV lidocaine arm and 25 in the Exparel arm. The record does not explain the difference between those entries, identify participants without outcome results, or describe their reasons for not contributing data. The analysis population and missing-data methods are not reported.

The endpoint descriptions are not fully aligned: the registry summary names postoperative pain and morphine equivalents as primary endpoints, while the posted outcome is the 4-week verbal pain score. No results are posted for morphine equivalents or the secondary measures listed in the summary. A clinical threshold for interpreting the score difference, the confidence level, and the method used for the confidence interval are not reported.

The trial-specific protocol and statistical plan are not reported in the registry record. This includes the original sample-size justification, outcome hierarchy, any multiplicity approach, and whether analyses were adjusted. The listed planning figures are illustrations from the observed effect, not evidence about the trial's original design. These limitations mean the posted outcome can be described, but its place in the complete planned analysis and its representativeness of all enrolled participants remain uncertain.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Pain Control in Colorectal Surgery: Liposomal Bupivacaine Block Versus Intravenous Lidociane — NCT04005859.
• Registry record last updated 2022-08-09; status last verified 2021-10.
• Results first posted 2021-10-22.
• 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

NCT04005859 is a completed phase 4 randomized, single-masked, parallel-group trial sponsored by Wake Forest University Health Sciences. It compared a preoperative Exparel TAP block with intravenous lidocaine given before and after surgery in colorectal surgery. The registry lists enrollment of 61.

The posted primary outcome is the verbal pain scale score at the 4-week postoperative visit or phone call, measured on a 0-to-10 scale. The mean was 0.4 in the IV lidocaine arm and 1.1 in the Exparel arm. The mean difference was 0.7, with a confidence interval from -0.126 to 1.526 and an unadjusted p-value of 0.097.

No secondary outcomes are posted. Missing-data procedures, the analysis population, and the trial-specific statistical plan are not reported in the registry record. The result is therefore best understood as an uncertain estimate for the stated pain assessment, rather than a complete account of all outcomes described in the registry summary.