Liposomal Bupivacaine in Implant Based Breast Reconstruction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Liposomal Bupivacaine in Implant Based Breast Reconstruction (NCT02659501), a randomized na study. The primary outcome is The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1..

2. Clinical Question

The trial also listed objectives concerning opioid consumption, opioid-related adverse events, hospital stay, satisfaction with pain control, and overall satisfaction. Although the registry record lists five outcome measures, it contains no posted secondary outcome results. The primary result therefore addresses only the registry’s stated average pain score endpoint at 24 hours, not the other objectives.

3. Trial Design

The registry record describes a randomized, single-masked, parallel-group trial sponsored by Loma Linda University. Enrollment was 24, with 12 participants assigned to the bupivacaine-with-epinephrine arm and 12 to the liposomal-bupivacaine arm. The record lists the study as terminated. The reason for termination is not reported in the registry record.

The recorded study start was 2015-07, and the primary completion date was 2016-09. The phase is listed as NA. The record does not state which participants or study personnel were masked, nor does it give details about sequence generation, allocation concealment, or the procedures used to maintain masking. These aspects should not be inferred from the labels “randomized” and “single masked.”

The control arm is described as receiving an intraoperative field block using bupivacaine with epinephrine, while the experimental arm is described as receiving an intraoperative field block using liposomal bupivacaine. Both arm descriptions also refer to postoperative pain control, but the descriptions are truncated. The exact postoperative regimens and any differences between them are not reported in the registry record.

The primary outcome was a continuous measure: average postoperative pain score at 24 hours. The registry reports group means and standard deviations, as well as an unadjusted mean difference with a confidence interval and p-value. It does not report an adjusted model or a detailed statistical analysis plan. The original sample-size assumptions, including any target effect or planned analysis, are not reported in the registry record. The separate sample-size figures are planning illustrations based on the observed result, not documented design assumptions.

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 The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1., measured over Average Pain Scores 24 hours Post-Operatively.

The primary endpoint is average postoperative pain score 24 hours after surgery. Pain was assessed on a numeric rating scale from 0 to 10, where 0 means no pain and 10 means the worst possible pain. Higher scores indicate a worse outcome. The registry says pain ratings were collected during routine vital signs every 4 hours after surgery and identifies the endpoint timeframe as average pain scores 24 hours post-operatively.

Averaging pain scores over the stated assessment period can represent pain burden more broadly than a single rating at one moment. It can also reduce the influence of temporary fluctuations in an individual rating. The specific averaging procedure, including which readings were included and how missing readings were handled, is not reported in the registry record.

Pain is a patient-reported symptom, so a numeric rating scale translates a subjective experience into a quantitative measure that can be compared between randomized groups. The scale’s direction matters for interpretation: higher values indicate worse pain, while lower values indicate less pain. The registry reports a mean for each arm and a comparison of those means. These summaries describe the group-level result; they do not show every participant’s experience or how scores varied over time.

The registry lists other objectives, but no secondary outcome results are posted. The primary endpoint result should therefore be interpreted as evidence about the stated pain-score measure at 24 hours, not as a result about opioid use, adverse events related to opioids, hospital stay, or satisfaction.

7. Results Posted in the Registry

• Liposomal Bupivacaine: mean 3.68 versus 3.66 on control; difference 0.02 (95% CI -0.77 to 0.81), standardized effect d = 0.02; z-test p = 0.960.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s pain is represented by a numeric score, and the registry reports the group mean and standard deviation. A mean summarizes the average score in a group. A standard deviation describes how spread out the individual scores are around that group mean. These quantities answer different questions: the mean describes the group’s central level, while the standard deviation describes within-group variation.

The reported effect is a mean difference, calculated in the stated comparison as the liposomal-bupivacaine mean minus the bupivacaine-with-epinephrine mean. A value of zero would correspond to equal sample means. A positive value means the liposomal-bupivacaine group had the higher mean; because higher scores indicate worse pain, that direction points toward a higher average pain score in that group. A negative value points toward a lower mean in the liposomal-bupivacaine group. This describes the scale’s direction, not a clinical judgment about importance.

The comparison is unadjusted, meaning the reported estimate compares the group summaries without a reported statistical adjustment for other variables. Random assignment is intended to create comparable groups on average, but in a small trial chance differences in participant characteristics can remain. The registry record does not report covariate-adjusted results, a model specification, or an analysis plan. It is therefore not possible to determine whether other analyses were planned or performed.

A confidence interval expresses uncertainty around an estimated effect. In general, a 95% confidence interval is produced by a procedure that, under its assumptions, would cover the underlying effect in 95% of repeated samples. It is not a statement that there is a 95% probability that this particular interval contains the true value. The interval reported for this comparison includes zero and covers values on both sides of zero. That means the posted data are compatible with different possible directions of the group difference, as well as with little or no difference. The interval’s width is important: a point estimate alone can look exact even when the data allow a broad range of plausible effects.

The unadjusted p-value describes how unusual results at least as incompatible with the null comparison would be under a statistical model in which the group means are equal. General statistical interpretation requires care: a p-value is not the probability that the null hypothesis is true, and it does not measure the probability that a result is clinically important. The reported value should be considered alongside the estimated difference and confidence interval, rather than used as a stand-alone conclusion.

The registry reports standard deviations of 0.33 and 1.35. Unequal observed spread can matter because standard errors and confidence intervals depend on variability. General methods for two-group mean comparisons can use a common variance assumption or allow group variances to differ. The registry does not identify which specific method was used for the sponsor’s reported comparison, so it is not appropriate to attribute a particular variance assumption to that analysis. The displayed uncertainty should be interpreted as the result recorded, without inferring unreported model details.

The outcome is described as an average pain score at 24 hours, with ratings collected every 4 hours during routine vital signs. Repeated measurements on the same participant are generally related rather than independent. A participant’s ratings across time may reflect a shared underlying pain experience, and a method that treats each rating as independent can misrepresent uncertainty. Here, however, the registry provides a group average endpoint and does not report the averaging rule or any repeated-measures model. General considerations about correlated repeated observations explain why those details can matter, but they do not establish which method was used.

Missing data can also affect an average endpoint. If some scheduled ratings are absent, the calculated average may depend on how many observations are available and on the reason for missingness. General approaches can use rules for complete observations, imputation, or statistical models, but the registry record does not report which approach was used or whether outcome values were missing. It does not report an analysis population either. Those details are needed to reproduce the analysis and assess sensitivity to missingness.

The sample-size illustrations use the observed effect as a starting point and consider stated fractions of that effect. General planning logic is that smaller target effects require more participants to distinguish them from random variation at a given significance level and power. These are planning calculations, not evidence about the trial’s original design or its achieved ability to detect an effect. The original design assumptions are not reported in the registry record.

10. Confidence Intervals and Precision

The estimated mean difference is 0.02 points, with a 95% confidence interval from -0.766 to 0.806. The interval is the key guide to precision: although the point estimate is close to zero, the data remain compatible with mean differences on either side of zero. The lower bound represents a lower average score in the liposomal-bupivacaine group relative to control; the upper bound represents a higher average score in that group.

A confidence interval is not a range containing every participant’s score. It describes uncertainty in the estimated group difference under the analysis used. It also does not show whether a difference would be important to patients. The registry does not report a threshold for a clinically meaningful difference, so the interval cannot be classified against such a threshold from this record alone.

The interval’s inclusion of zero is consistent with the unadjusted p-value of 0.96, but neither result proves equivalence. Establishing equivalence or non-inferiority ordinarily requires a prespecified margin and a design and analysis appropriate to that question. Such a margin or framework is not reported in the registry record.

Both groups had 12 participants. With this group size, estimates can be imprecise, particularly when observations vary. The reported standard deviation was 0.33 in the control arm and 1.35 in the liposomal-bupivacaine arm. The larger observed spread in the latter group contributes important context when considering how much confidence to place in its mean and the estimated difference. The record does not include participant-level scores or further sensitivity analyses.

In practical statistical terms, the point estimate alone gives a narrow-looking summary, but the interval communicates that the underlying group difference is uncertain. The result does not tightly pin down the direction or magnitude of a difference in average pain score.

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 figures are planning illustrations based on the observed effect, not the trial’s own original design calculation. The registry record does not report the trial’s original sample-size assumptions or justification. For this continuous outcome, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each calculation targets a stated fraction of the observed effect.

The 80% power column gives the planned number of participants per arm for a hypothetical study designed so that, if the target effect and assumptions were correct, the analysis would have an 80% chance of detecting an effect at the stated significance level. The 90% power column gives the corresponding per-arm number for a higher chance of detection under those same assumptions. Power is a design concept conditional on the effect and model used; it does not indicate the probability that the observed result is true.

Planning for 100% of the observed effect uses that observed effect as the target. Planning for 75% or 50% of the observed effect sets a smaller target. Smaller effects are harder to distinguish from random variation, so the planning figures rise as the target effect becomes smaller. The displayed values are very large because the observed difference is close to zero, making a fraction of that effect especially small. These calculations should not be treated as a recommendation or as evidence that the trial was designed to enroll those numbers.

This is not observed power. It is a forward-looking illustration under stated assumptions, whereas the trial’s observed result is the estimated mean difference and its confidence interval.

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 = 0.020; pooled standard deviation σ = 0.983.
2. n = 2 × (1.96 + 0.842)² × 0.983² / 0.020² = 37,898.3, rounded up to 37,899 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 <- 0.02                      # observed difference in means
sigma <- 0.982700361249552                     # 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(2659501)
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 = 37,899 (80% power), 50,736 (90% power)
 75% of observed effect: n per arm = 67,375 (80% power), 90,196 (90% power)
 50% of observed effect: n per arm = 151,594 (80% power), 202,941 (90% power)
power.t.test: 37899.3 
Simulated power at n = 37,899 per arm: 0.801 (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 five outcome measures and describes objectives beyond the primary pain endpoint, including opioid consumption, opioid-related adverse events, length of hospital stay, and patient satisfaction. No secondary outcome results are posted, and the record reports no posted analyses. Therefore, the multiplicity strategy for testing several outcomes is not reported in the registry record. It is not possible to determine whether any adjustments for multiple comparisons were planned or used.

Multiplicity matters in general because conducting many statistical tests can increase the chance that at least one appears noteworthy by chance. Possible approaches include identifying one primary endpoint in advance, adjusting inference across a set of outcomes, or treating other outcomes as exploratory. The registry identifies a primary endpoint but does not report enough about the analysis plan to establish how the remaining objectives were handled. The unadjusted p-value for the primary comparison should not be assumed to represent an adjustment across all objectives.

The registry record does not state whether any primary endpoint measurements were missing, how missing measurements were handled, or which analysis population was used. It does not describe whether participants were analyzed according to randomized assignment, whether all randomized participants contributed an endpoint value, or whether any exclusions occurred. These details affect interpretation and reproducibility, but none should be inferred from the arm counts alone.

The record also does not specify whether repeated pain ratings were reduced to an average using all scheduled readings, only available readings, or another rule. Nor does it report a sensitivity analysis for missing ratings or alternative analysis populations. Consequently, the posted summary permits interpretation of the stated group means and comparison, but not a full audit of missing-data decisions or the handling of multiple outcomes.

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.

The registry reports zero serious adverse events among 12 participants at risk in the bupivacaine-with-epinephrine arm and zero among 12 participants at risk in the liposomal-bupivacaine arm. It also reports zero other adverse events among 12 participants at risk in each arm. These are the event counts recorded for the categories shown.

Zero reported events does not establish that an intervention has no risk. In a small study, uncommon events may not occur among enrolled participants even when they could occur in a broader population. These counts also do not describe event severity beyond the registry’s serious-versus-other categories, timing, or relationship to treatment. No serious adverse-event terms are listed.

Death counts are not reported in the registry record. The posted safety figures should be read as registry summaries, not as a complete account of all possible harms or as evidence that the groups have identical safety profiles. The record does not provide further detail on the methods used to collect or classify adverse events.

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

The posted primary result describes similar observed average pain scores at 24 hours: 3.66 in the bupivacaine-with-epinephrine arm and 3.68 in the liposomal-bupivacaine arm. The estimated difference was 0.02, with a 95% confidence interval from -0.766 to 0.806 and an unadjusted p-value of 0.96. The interval includes zero and leaves uncertainty about both direction and size. This is a description of the registry’s posted result, not a conclusion that the treatments are equivalent.

The result applies to the specific recorded endpoint, population, and trial comparison. It does not describe pain at other times, individual participant experiences, or any outcome beyond average pain score at 24 hours. The registry lists objectives about opioid use, opioid-related adverse events, length of stay, and satisfaction, but posts no secondary outcome results. Those questions therefore remain unanswered by the results recorded.

The study enrolled 24 participants, with 12 in each arm, and is listed as terminated. The reason for termination is not reported in the registry record. Small group sizes and the observed difference in score variability contribute to uncertainty in the estimates. The record does not provide enough detail about missing data, analysis populations, or the statistical analysis plan to assess those aspects fully.

General interpretation of randomized comparisons considers the estimated effect, its uncertainty, design, and conduct together. A high p-value does not demonstrate that there is no effect; a low p-value would not by itself establish clinical importance. The confidence interval is more informative about the range of effects compatible with this result, while the absence of a reported meaningful-difference threshold limits judgment about practical importance.

Accordingly, the registry supports a cautious reading: it reports a near-zero point estimate for this pain-score comparison, but the estimate is not precise enough to establish the absence, direction, or clinical importance of a difference. It does not support claims about unreported outcomes or broader treatment effects.

16. Why This Trial Matters Statistically

This trial illustrates why a point estimate and a p-value should not be interpreted alone. The mean difference of 0.02 looks close to zero, and the unadjusted p-value is 0.96. But the confidence interval, from -0.766 to 0.806, shows that the estimate remains compatible with differences in either direction. Statistical interpretation depends on both the estimated effect and its precision.

The group summaries also show unequal observed variability: the standard deviation was 0.33 in the control group and 1.35 in the liposomal-bupivacaine group. That difference draws attention to the distribution of observations, not just the average. General statistical practice treats variability as central to uncertainty, particularly when group sizes are limited. The registry record does not report individual scores or the specific method used to address variance differences.

The case also highlights the distinction between a registered objective and a posted result. Several outcomes were listed, but only the primary pain endpoint has results in the record. Without secondary results, statistical conclusions cannot be extended to opioid use, hospital stay, or satisfaction. Similarly, a listed randomized and single-masked design does not by itself document allocation procedures, which party was masked, missing-data handling, or analysis populations.

Finally, planning illustrations derived from an observed effect are not evidence about the original study design or about achieved power. They demonstrate how a small target effect can require a larger planned sample under specified assumptions, but they cannot replace a prospectively justified sample-size calculation. Taken together, the registry record is a useful example of reading a result through its uncertainty and its reporting limits rather than treating a single test statistic as a complete answer.

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 contains limited detail for evaluating how the trial was conducted and analyzed. It identifies randomization and single masking but does not describe sequence generation, allocation concealment, or which participants or personnel were masked. The reason the trial was terminated is not reported. These omissions limit assessment of potential sources of bias and the context in which the results were collected.

The arm descriptions are truncated, particularly for postoperative care. The exact co-interventions and whether postoperative regimens were the same across groups are not reported in the registry record. The record also does not give participant eligibility criteria, baseline characteristics, or detail on the surgical procedures. These gaps restrict evaluation of how representative the enrolled participants were and how readily the result applies beyond the recorded setting.

For the primary endpoint, the record does not describe the exact rule used to calculate the 24-hour average, the number of ratings included for each participant, or how any missing ratings were handled. It does not identify the analysis population or provide the detailed statistical plan. No participant-level data or additional sensitivity analyses are posted. The registry also lacks results for the other listed objectives.

The enrolled group was small, and the confidence interval for the mean difference includes values on both sides of zero. The result therefore has limited precision. The registry does not report a threshold for a clinically important pain-score difference, which prevents assessment of the interval against such a threshold. These limitations do not invalidate the recorded summaries, but they constrain how much can be concluded from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Liposomal Bupivacaine in Implant Based Breast Reconstruction — NCT02659501.
• Registry record last updated 2021-01-12; status last verified 2020-12.
• Results first posted 2019-08-21.
• 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 concerns a randomized, single-masked, parallel-group trial of liposomal bupivacaine versus bupivacaine with epinephrine for postoperative pain in implant-based breast reconstruction. It lists enrollment of 24, with 12 participants in each arm, and is marked terminated. The recorded start was 2015-07, and primary completion was 2016-09.

The primary endpoint was average pain score 24 hours after surgery on a 0-to-10 numeric rating scale. The reported means were 3.66 for bupivacaine with epinephrine and 3.68 for liposomal bupivacaine. The mean difference was 0.02, with a 95% confidence interval from -0.766 to 0.806 and an unadjusted p-value of 0.96. The registry also reports zero serious and zero other adverse events in each arm; death counts are not reported.

The reason for termination, original design assumptions, detailed analysis plan, missing-data handling, and results for secondary objectives are not reported in the registry record.