Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL in Total Knee Arthroplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL in Total Knee Arthroplasty (NCT02713178), a randomized phase 3 study. The primary outcome is Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores Through 72 Hours.

2. Clinical Question

3. Trial Design

The registry describes a completed Phase 3, multicenter, randomized, double-blind, placebo-controlled study with a parallel-group design and triple masking. It enrolled 232 participants. The trial addressed postsurgical analgesia in adults undergoing primary unilateral total knee arthroplasty, performed under general or spinal anesthesia.

There were three study arms: EXPAREL 133 mg, EXPAREL 266 mg, and placebo. The 133 mg dose was expanded with normal saline to a total volume of 20 mL; the 266 mg dose was given in 20 mL; and placebo was 20 mL of normal saline. The record describes the intervention as femoral nerve block with EXPAREL. It does not report further procedural details about block administration.

Randomization assigned participants to treatment groups, and the primary efficacy analysis was based on randomized treatment. The efficacy population was defined as participants who received study drug and underwent surgery. The reported group sizes for the primary outcome were 75 for EXPAREL 133 mg, 76 for EXPAREL 266 mg, and 79 for placebo. These are outcome-analysis group counts, not a replacement for the registry’s overall enrollment figure.

The registry lists a primary pain-intensity outcome and secondary outcomes concerning opioid consumption, opioid-free participants, and time to first opioid rescue. Primary completion was recorded as 2017-06-30, and study status is completed. The original statistical design assumptions, including any planned sample-size justification, 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: Efficacy population: all participants who received study drug and underwent the surgery, with analysis based on randomized treatment

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.

Population: Safety population included all participants who received study drug, with analysis by actual treatment received.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores Through 72 Hours, measured over 0-72 hours.

The primary endpoint was the area under the curve (AUC) of Visual Analog Scale pain intensity scores through 72 hours, with a timeframe of 0–72 hours. The Visual Analog Scale was a straight 10 cm line anchored at 0 cm for no pain and 10 cm for the worst pain possible. Participants were asked to mark the line to indicate their current pain.

An AUC condenses repeated measurements across an interval into a single measure. It reflects both the level of recorded pain and how that level is represented across the measurement period, rather than relying on a single pain rating at one moment. For this endpoint, the unit is cm*hr. A lower AUC represents a lower accumulated pain-intensity score over the stated interval.

The registry reports least-squares means and standard errors for each group. Least-squares means are model-based group means; their interpretation depends in part on the analysis model. The registry identifies ANOVA for the sponsor’s primary comparisons, but details of model covariates and other modeling choices are not reported in the registry record.

Using an interval-based endpoint can summarize a postoperative symptom that changes over time. It also means the single AUC estimate does not reveal the timing or shape of pain ratings within the interval. The registry record does not report a threshold for a clinically meaningful difference on this AUC measure.

7. Results Posted in the Registry

• EXPAREL 133 mg: mean 259.55 versus 279.79 on control; difference -20.25 (95% CI -72.23 to 31.73), standardized effect d = -0.12; z-test p = 0.445.
• EXPAREL 266 mg: mean 251.00 versus 279.79 on control; difference -28.80 (95% CI -80.55 to 22.96), standardized effect d = -0.18; z-test p = 0.275.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Total Postsurgical Opioid Consumption Through 72 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • EXPAREL 133 mg: mean 69.47 versus 81.47 on control; difference -12.00 (95% CI -25.07 to 1.06), standardized effect d = -0.29; z-test p = 0.072.
  • EXPAREL 266 mg: mean 74.39 versus 81.47 on control; difference -7.08 (95% CI -20.49 to 6.34), standardized effect d = -0.17; z-test p = 0.301.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between EXPAREL 133 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between EXPAREL 266 mg and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes cover related but distinct aspects of postsurgical recovery: total opioid consumption through 72 hours, the percentage of opioid-free participants through 72 hours, and time to first opioid rescue through 72 hours. Opioid consumption complements pain-intensity ratings by recording medication use, while opioid-free status and time to rescue describe whether and when rescue medication was used.

The numeric information in the registry supports a comparison for total opioid consumption. Across its active-dose comparisons, the point estimates are below placebo, but the recalculated uncertainty intervals include no difference. This directional pattern is compatible with the lower primary AUC point estimates, but neither outcome alone establishes a reliable treatment difference. Numeric results for opioid-free participants and time to first opioid rescue are not reported in the registry record, so their direction and precision cannot be assessed from the registry entries.

Secondary outcomes can help characterize the broader result, but they carry less weight than the prespecified primary question when multiple outcomes are examined. Each additional comparison creates another opportunity for a chance finding. Without a reported multiplicity procedure, isolated secondary results should not be treated as confirmatory evidence. The registry does not report whether adjustments were made across secondary outcomes or analyses.

These outcomes also measure different constructs and may not move in lockstep. Pain ratings, opioid use, and time to rescue are related, but one is not a direct substitute for another. The secondary findings should therefore be considered alongside, rather than used to override, the primary endpoint and its uncertainty.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Total Postsurgical Opioid Consumption Through 72 Hours
• Percentage of Opioid-free Participants Through 72 Hours
• Time to First Opioid Rescue Through 72 Hours

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is an AUC measured in cm*hr, and the registry reports least-squares means with standard errors. The sponsor’s primary comparisons are identified as ANOVA analyses, with least-squares mean differences as the reported comparison measure. The following concepts explain how to read those statistics; they do not add unreported details about the trial’s analysis plan.

What does a least-squares mean describe?

A least-squares mean is a model-based estimate of a group mean. In an analysis of variance, the model compares group outcomes while representing the variation in the observations under the model’s assumptions. A model-based mean can differ from a simple arithmetic mean if the model accounts for other factors. The registry does not report the covariates or full model specification, so the reported least-squares means should be interpreted as the trial’s model-based estimates without assuming which adjustments were used.

The reported group estimates are 259.5 cm*hr for EXPAREL 133 mg, 251.0 cm*hr for EXPAREL 266 mg, and 279.8 cm*hr for placebo. The reported standard errors are 19.01, 18.85, and 18.49, respectively. A standard error describes the estimated sampling uncertainty of a mean: it reflects how much the estimate would tend to vary across repeated samples under the statistical model. It is not the spread of individual participant outcomes.

What does a mean difference represent?

A mean difference compares an active treatment estimate with the placebo estimate on the outcome’s original scale. Negative differences in these comparisons mean that the active-group AUC estimate is lower than the placebo estimate. That direction describes the arithmetic ordering of the estimates; it does not, on its own, establish a treatment effect or clinical importance.

The recalculated comparisons use the posted summary estimates and are unadjusted. For EXPAREL 133 mg versus placebo, the recalculated difference is -20.25 cm*hr; for EXPAREL 266 mg versus placebo, it is -28.8 cm*hr. These simple comparisons do not replace the sponsor’s ANOVA analysis. Their role is to provide a transparent check using the posted summary statistics, while the registry’s reported analysis remains the trial analysis.

How should a confidence interval be read?

A confidence interval expresses uncertainty around an estimated comparison. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision, under the method used to construct it. A 95% confidence interval is a procedure that, under its assumptions, would cover the underlying value in 95% of repeated samples. It is not a statement that a particular interval has a 95% probability of containing the true value.

For the recalculated primary comparisons, the intervals extend from -72.23 to 31.73 cm*hr and from -80.55 to 22.96 cm*hr. Each includes zero, the value representing no mean difference. Thus the intervals encompass both a lower AUC with EXPAREL and a higher AUC with EXPAREL relative to placebo. The estimates are not precise enough to exclude either direction over the range of values in those intervals.

What does a p-value add?

A p-value measures how compatible the data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The recalculated unadjusted p-values are 0.445 and 0.275 for the two primary comparisons. Their interpretation should be considered alongside the estimates and confidence intervals, rather than in isolation.

The registry reports an ANOVA method for the primary comparisons. It does not report all details needed to reproduce the sponsor’s model, such as covariate selection, treatment of missing measurements, or diagnostics. The unadjusted recalculation is based on summary measures and is therefore not a reconstruction of the full trial analysis.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model expects. If a model understates variability, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. If variability is larger than expected, methods that allow for it can better reflect uncertainty. The registry record does not identify over-dispersion as an issue for this endpoint or report a special correction for it; this is a general consideration, not a claim about this trial.

Finally, the trial used randomized treatment assignment for the stated efficacy population, which helps define the comparison. The population still excludes participants who did not meet the recorded criteria of receiving study drug and undergoing surgery. The registry does not report how missing outcome observations were handled or whether additional analysis populations were used.

11. Confidence Intervals and Precision

The primary comparisons are imprecise relative to their point estimates. For EXPAREL 133 mg versus placebo, the recalculated mean difference is -20.25 cm*hr, with a 95% confidence interval from -72.23 to 31.73. For EXPAREL 266 mg versus placebo, the difference is -28.8 cm*hr, with a 95% confidence interval from -80.55 to 22.96. Both intervals include zero and extend to values on either side of it.

These intervals show why the direction of the point estimates should not be treated as settled. The estimates are lower for the active groups, but the intervals also include the possibility of higher AUC relative to placebo. The interval endpoints describe uncertainty in the comparison, not the range of individual participants’ pain scores. The reported group standard errors also refer to the precision of estimated group means, not the dispersion of participant responses.

The sponsor’s reported 95% confidence intervals for both primary comparisons likewise include no difference. The sponsor estimates and the unadjusted recalculations are close, though their exact values differ slightly because the analyses are not identical. The registry reports no discrepancy. The sponsor’s model-based analysis and its uncertainty estimates should therefore be read as the trial’s formal results, with the recalculations serving as a summary-statistic check.

The registry record does not report a minimally important AUC difference. Consequently, statistical uncertainty cannot be translated from these registry entries into a firm judgment about clinical importance. The interval bounds are best read as a range of values compatible with the analysis, not as a guarantee that the true difference lies within them.

12. 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 figures are planning illustrations expressed as participants per arm, not total event counts. They use the observed effect as a starting point and consider planning for 100%, 75%, or 50% of that observed effect. For each assumed effect, the figures give participants per arm for 80% power and participants per arm for 90% power. The 80% power column represents a design that would have an 80% chance of detecting the specified effect under the stated assumptions; the 90% column represents a higher chance of detecting it, which generally requires more participants.

The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. These figures are not the trial’s original sample-size calculation. The trial’s own design assumptions and sample-size justification are not reported in the registry record. This is not observed power.

The figures increase as the assumed effect becomes smaller: planning to detect a smaller fraction of the observed effect requires more participants per arm under the same assumptions. This is a general property of statistical planning, not evidence that the trial had a particular probability of success after completion. The illustrations are also pairwise: they concern one comparison at a time, rather than a single sample-size target for all trial arms or outcomes. They should be interpreted as planning scenarios, not as a judgment about whether the completed study was adequate for its original purpose.

13. 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 = -20.249; pooled standard deviation σ = 164.501.
2. n = 2 × (1.96 + 0.842)² × 164.501² / -20.249² = 1,036.0, rounded up to 1,037 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 <- -20.249                      # observed difference in means
sigma <- 164.501228108678                     # 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(2713178)
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 = 1,037 (80% power), 1,387 (90% power)
 75% of observed effect: n per arm = 1,842 (80% power), 2,466 (90% power)
 50% of observed effect: n per arm = 4,145 (80% power), 5,548 (90% power)
power.t.test: 1037 
Simulated power at n = 1,037 per arm: 0.798 (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.

14. Analyses Reported by the Sponsor

The sponsor’s primary analyses use ANOVA and report least-squares mean differences for each EXPAREL dose versus placebo. Both reported comparisons favor lower AUC estimates in the active groups, and both reported 95% confidence intervals include no difference. The sponsor’s reported p-values are close to the unadjusted p-values from the recalculations.

The recalculations use the posted group means and standard errors to make simple unadjusted comparisons. They are not a reproduction of the sponsor’s full model, and their confidence limits and p-values differ slightly from the reported analysis. The registry record indicates no discrepancy between the posted results and the recalculations. The sponsor’s own ANOVA analysis is the trial’s formal analysis; the recalculation is a supplementary check on the direction and scale of the comparison.

For the primary endpoint, both approaches give a similar overall reading: estimates are lower with EXPAREL than with placebo, while the uncertainty intervals do not exclude no difference. The recalculations cannot establish whether the sponsor’s model included covariates or other analytic features beyond those named in the registry. Such details are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, treatment comparison, time point, or analysis. As the number of statistical tests grows, the chance of at least one apparently noteworthy result arising by chance can increase. This is a general statistical concern; it does not mean that any particular result in this trial is false.

The registry lists four outcome measures and six analyses. It identifies one primary outcome and three secondary outcome topics. The two active doses are each compared with placebo for the primary endpoint, and the posted secondary information includes comparisons for opioid consumption. The registry record does not report whether a family-wise error procedure, a hierarchical testing sequence, or another multiplicity strategy was used. It is therefore not possible to determine from the record how the sponsor intended to control the interpretation of multiple tests.

Missing-data handling is also not reported in the registry record. The primary efficacy population is defined as participants who received study drug and underwent surgery, analyzed according to randomized treatment. That definition describes population eligibility, but it does not explain how missing pain ratings within the 0–72 hour interval were treated, whether incomplete AUC records were excluded or imputed, or how any sensitivity analyses addressed missingness.

The registry also does not report the full set of analysis populations, model covariates, or detailed assumptions used in the sponsor’s ANOVA. Those omissions limit independent assessment of the analysis process. They do not alter the posted point estimates or intervals, but they mean that the formal analysis cannot be fully reconstructed from the registry record alone.

Interpretation should consequently distinguish the primary endpoint from the additional outcomes and recognize that unreported multiplicity and missing-data methods leave important uncertainties about the broader analysis plan. No particular correction or missing-data method should be presumed.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: postprocedural hematoma (4.0%), motor dysfunction (2.6%), atrial fibrillation (1.3%), postprocedural swelling (1.3%), cellulitis (1.3%).

The safety summary reports serious adverse events for each study arm. Serious adverse events affected 5 of 75 participants in the EXPAREL 133 mg group, 8 of 76 in the EXPAREL 266 mg group, and 6 of 79 in the placebo group. These are counts among the participants recorded at risk in each arm. The registry reports 0 deaths in each group.

Other adverse events were recorded for 73 of 75 participants in the EXPAREL 133 mg group, 74 of 76 in the EXPAREL 266 mg group, and 76 of 79 in the placebo group. The serious-event terms listed in the record include postprocedural hematoma (4.0%), motor dysfunction (2.6%), atrial fibrillation (1.3%), postprocedural swelling (1.3%), cellulitis (1.3%), and sinus bradycardia (1.3%). Arm-specific counts for each listed term are not reported in the registry record.

These figures describe events recorded during the study; they do not, by themselves, establish that a treatment caused an event. The summary does not provide event timing, severity gradations, attribution, or detailed follow-up in the registry record for this analysis. Comparisons should therefore remain descriptive, especially where counts are limited.

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

The posted primary estimates are lower for EXPAREL 133 mg and EXPAREL 266 mg than for placebo on the 0–72 hour pain-intensity AUC. The sponsor’s comparisons and the unadjusted recalculations point in the same direction. However, the confidence intervals for both comparisons include no difference and span values that favor either side. The data therefore do not precisely determine the direction or size of the underlying difference.

This does not mean the groups are proven equal. A failure to distinguish a difference from zero is not an equivalence result. Establishing equivalence or non-inferiority would require a specified margin and an analysis designed for that question; such a margin is not reported in the registry record. Conversely, a lower point estimate is not sufficient evidence that the difference is important to patients. A clinically meaningful threshold for the AUC measure is not reported.

The primary endpoint summarizes pain ratings over a defined postoperative interval. It does not describe pain beyond that interval, the full time course of ratings, or every aspect of recovery. The secondary outcomes concern opioid use and rescue medication, but numeric results for two of the listed secondary outcomes are not reported in the registry record. The safety summary provides event counts and selected serious-event terms, not a causal determination.

The registry record supports a careful statistical reading of the posted comparisons, not medical advice or a treatment recommendation. The findings are specific to the enrolled population, the procedures and treatment arms described, and the outcomes recorded. They should not be generalized beyond those details without additional evidence.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through both its point estimate and its uncertainty. The primary group estimates are ordered in favor of lower AUC with both active doses, yet the intervals around the comparisons include zero and extend across values in both directions. A directional estimate is informative, but precision determines how confidently its size and direction can be distinguished from uncertainty.

The endpoint also demonstrates the trade-off in using a summary measure. AUC can combine pain ratings across the postoperative interval into a single outcome that supports a treatment comparison. At the same time, it can conceal when ratings differed and how the trajectory changed. Readers need to interpret the measure within its stated timeframe and not treat it as a complete account of pain or recovery.

The trial further shows how primary and secondary outcomes answer related but non-identical questions. Pain intensity and opioid use may provide complementary information, while opioid-free status and time to rescue capture other aspects of medication use. Multiple endpoints and comparisons make it important to know the testing plan, yet multiplicity methods are not reported in the registry record. That absence limits the strength of conclusions drawn from secondary findings.

Finally, the sample-size illustrations clarify that planning depends on the effect a study aims to detect. Smaller assumed effects require more participants under the listed planning assumptions. Those illustrations are separate from the completed trial’s original design, whose assumptions are not reported. Together, these statistical features show why effect estimates, intervals, analysis details, and planning assumptions all matter when assessing clinical-trial evidence.

19. 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 limits affect interpretation. The registry identifies a multicenter study but does not report the number of participating centers. The original sample-size justification and design assumptions are not reported, so the planning illustrations cannot be used to reconstruct the trial’s intended detectable effect or original power target.

The primary outcome is an AUC through 72 hours. It summarizes ratings over that interval but does not, by itself, show how pain changed within it. The registry record does not report a clinically meaningful threshold for the AUC measure, making it difficult to judge whether a given numerical difference would matter to participants.

The record identifies ANOVA for the sponsor’s primary analysis but does not provide the full model specification, covariates, missing-data method, or sensitivity analyses. It also does not report a multiplicity strategy for the several outcomes and analyses. These omissions limit independent appraisal and reproducibility, though the sponsor estimates and the recalculated summary-statistic comparisons are close.

The posted summary provides detailed primary results and numeric information for total opioid consumption, but numeric results for opioid-free participants and time to first opioid rescue are not reported in the registry record. Pharmacokinetic results are not reported in the registry record despite pharmacokinetics appearing in the study title. The safety information is a summary of event counts and selected serious-event terms; attribution and arm-specific counts for the listed terms are not reported.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL in Total Knee Arthroplasty — NCT02713178.
• Registry record last updated 2020-12-01; status last verified 2020-11.
• Results first posted 2020-12-01.
• 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.

23. Record Summary

The registry record describes a completed, randomized, double-blind, placebo-controlled Phase 3 study of femoral nerve block with EXPAREL in adults undergoing primary unilateral total knee arthroplasty. The primary outcome was pain-intensity AUC through 72 hours. Group estimates were lower for both EXPAREL doses than for placebo, but the reported and recalculated confidence intervals include no difference.

The trial also listed opioid-use outcomes and reported serious adverse event counts by arm. Important details, including the original sample-size justification, missing-data methods, multiplicity strategy, and numeric results for two listed secondary outcomes, are not reported in the registry record.