Study of EXPAREL in Patients Undergoing Breast Augmentation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of EXPAREL in Patients Undergoing Breast Augmentation (NCT01582490), a non-randomized phase 4 study. The primary outcome is Duration of Analgesia.

2. Clinical Question

The clinical question concerns the administration technique rather than a comparison between EXPAREL and an untreated group or another drug. Both groups received EXPAREL, but the method of administration differed. The registry describes instillation as Group 1 and infiltration as Group 2, in a prospective, open-label, non-randomized, sequential study.

The primary outcome is duration of analgesia as operationally defined in the record: the time from the end of surgery to the participant’s first postsurgical opioid administration. The population description notes that some participants were censored and therefore did not contribute an observed opioid-administration time to the stated efficacy analysis. The registry does not report the group estimates for this endpoint or an inferential comparison between groups.

Because assignment was not randomized, differences between the groups cannot be attributed to administration technique alone from the registry information. The record does not report how participants entered each sequential group or whether other factors differed between them. The results therefore need to be read as a description of two study groups, not as a definitive estimate of a causal treatment effect.

3. Trial Design

This was a Phase 4, prospective, open-label, non-randomized, sequential study in subjects undergoing bilateral augmentation mammoplasty. The record describes two treatment groups that differed in the technique used to administer EXPAREL: instillation or infiltration. Allocation is listed as non-randomized, masking as none, and the model as single group. Those labels do not make the two techniques a randomized comparison; the record itself cautions that the arms are not a like-for-like control comparison.

The listed enrollment was 19. For the primary endpoint, the efficacy analysis set included 8 subjects in the infiltration group and 9 in the instillation group. In the safety listing, the at-risk totals were 8 for infiltration and 10 for instillation. These are different reported populations, and the registry does not reconcile the difference or explain the status of every enrolled participant.

The treatment descriptions identify EXPAREL in both groups. For infiltration, diluted EXPAREL was to be administered by local infiltration; for instillation, diluted EXPAREL was to be placed into each breast pocket at the beginning of surgery. The descriptions specify a 20 mL vial containing 266 mg, diluted with 20 mL of preservative-free 0.9% normal saline to a total of 40 mL. The infiltration description is truncated in the registry text after the reference to each surgical site, so further procedural detail is not reported in the registry record.

The study status is completed. The listed start and primary completion are 2012-04 and 2012-11. The record lists 8 outcome measures, including the primary duration measure and secondary outcomes concerning opioid consumption, pain assessments, discharge timing, opioid-related adverse events, and satisfaction with postsurgical pain control. The registry record does not report the reason for the sequential design, the rationale for the allocation process, or a protocol for comparing the groups.

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: Of the 8 subjects in the Infiltration - EXPAREL group (efficacy analysis set), 5 were censored, leaving 3 subjects who were administered an opioid. Of the 9 subjects in the Instillation - EXPAREL group (efficacy analysis set), 7 were censored, leaving 2 subjects who were administered an opioid.

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: 19 subjects were enrolled, 9 in the Infiltration - EXPAREL group and 10 in the Instillation - EXPAREL group.

6. Primary Endpoint

The registry lists the primary outcome as Duration of Analgesia, measured over 10 days.

The primary endpoint is duration of analgesia, measured in hours from the end of surgery to the participant’s first postsurgical opioid administration. This is a time-to-event outcome: the event is the first opioid administration, and the measured time is the interval until that event. The endpoint converts the timing of a postoperative medication event into a defined outcome that can be summarized across participants.

Its interpretation is specific to the operational definition. It does not directly measure a continuous pain score, and the registry’s description does not define it as the time when pain first began or when a participant first requested medication. It records the time to the first opioid administration. Other listed outcomes address pain intensity at waking in the post-anesthesia care unit and at hospital discharge, opioid consumption, discharge timing, adverse events, and satisfaction.

The record says that 5 of 8 participants in the infiltration efficacy set and 7 of 9 in the instillation efficacy set were censored, leaving 3 and 2 participants, respectively, who were administered an opioid. Censoring means that an event time was not observed in the way required for the endpoint analysis during the available observation period. It is not the same as observing an event at a particular time. The registry does not report the endpoint estimates, the censoring rules, or how censoring was handled in the analysis.

The endpoint is useful for describing when the first opioid administration occurred, but its meaning depends on the study’s measurement and analysis procedures. Those procedures are not reported in the registry record in enough detail to assess the endpoint estimates or their precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record provides a primary endpoint definition and participant counts, but it does not report a statistical analysis plan, an analysis method for the primary endpoint, or inferential results. The explanations below describe general statistical concepts relevant to the endpoint and design; they do not assert that a particular method was used in this study.

What kind of endpoint is this?

In general, a time-to-event endpoint measures the time until a defined event. Here, the event is a participant’s first postsurgical opioid administration, and the time origin is the end of surgery. Time-to-event methods can use information from participants whose event was observed and from participants whose event time is censored. This distinction is important because censoring does not tell us the exact event time. The registry reports censored counts but does not state the censoring rules or the method used to summarize these observations.

Some common summaries for time-to-event data describe the probability of remaining event-free over time, or compare event timing between groups. Other approaches summarize a typical event time when that quantity can be estimated. Which summary is appropriate depends on the analysis plan, data, and assumptions. The registry does not report which summary was used for duration of analgesia, so none should be attributed to this study based on the endpoint definition alone.

Why does censoring matter?

In general, censored observations contribute incomplete information rather than a fully observed event time. Analyses can use them, but the result depends on how censoring is handled and on assumptions about why follow-up ended or why the event was not observed. If censoring is related to a participant’s chance of experiencing the event, that relationship can affect interpretation. The registry does not report why the listed participants were censored, whether follow-up differed by group, or whether the censoring assumptions were assessed.

The counts in the endpoint description indicate that most participants in each stated efficacy set were censored. Counts alone cannot reconstruct the timing distribution or determine the effect estimate. The registry does not report event times, group-level duration estimates, or uncertainty intervals. It is therefore not possible from this record to evaluate the precision of the primary result or the sensitivity of that result to censoring.

What does the non-randomized design imply?

In general, randomization helps balance measured and unmeasured prognostic characteristics across groups on average. Non-randomized assignment does not offer that protection. Sequential enrollment can also make group membership coincide with changes over time, although the registry does not say whether any such changes occurred. Differences in participant characteristics, surgical practice, care, or other factors could contribute to an observed group difference. The record does not describe adjustment for these factors or report a covariate-adjusted analysis.

Open-label status means masking was listed as none. In general, awareness of the assigned technique may influence care processes or outcome measurement, depending on how those are conducted. The primary endpoint is based on opioid administration, which is a recorded event, but the registry does not explain decisions about administration or whether outcome assessment was blinded. This is a possible source of interpretive uncertainty, not evidence that bias occurred.

What can the sample-size illustration tell us?

The sample-size section is described as a planning illustration computed from the observed effect, rather than the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; for time-to-event tables, the stated quantity is the total number of events. Such illustrations ask what sample size might be needed under specified assumptions. They are not observed power and do not show that the study was designed with those assumptions.

The illustration cannot resolve limitations in the original design or establish that a planned sample was achieved. In particular, the record does not report the trial’s own sample-size justification, a prespecified effect size, or the statistical plan that guided enrollment. Any sample-size figure shown in the calculated section should therefore be understood as a planning illustration, not as a measured property of the study or as evidence that the analysis was adequately powered.

What is not reported about the analysis?

The registry lists 8 outcome measures and 0 analyses. It does not report the method used to compare groups, handling of censoring, covariate adjustment, assumptions, missing-data strategy, or multiplicity procedure. It also does not report the primary outcome’s group estimates or inferential statistics. General statistical methods can explain how such analyses might be conducted, but without the analysis details they cannot establish what the investigators did. The registry record is not a substitute for a prespecified protocol or a detailed statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures: duration of analgesia as the primary outcome and 7 secondary outcomes concerning opioid consumption, pain intensity, discharge timing, opioid-related adverse events, and satisfaction with postsurgical pain control. The record lists 0 analyses. It does not report whether all outcomes were analyzed, which comparisons were prespecified, or how multiple outcomes or repeated assessments were handled. A multiplicity adjustment or a decision not to adjust is not reported in the registry record.

In general, evaluating many outcomes can increase the chance that at least one result appears notable by chance when each is considered separately. Prespecifying a primary outcome and a testing strategy can help readers distinguish a main confirmatory question from additional descriptive questions. Here, the registry identifies a primary outcome but does not provide the statistical plan needed to determine how the family of outcomes was interpreted. The mere presence of secondary outcome names does not show that an analysis was completed or that a particular finding was statistically significant.

The primary outcome description explicitly reports censored observations. It does not describe other missing data, reasons for missingness, follow-up completeness, or any imputation or sensitivity analyses. The record does not explain whether outcome data were available for every enrolled participant or why the efficacy and safety populations differ. These details are important because the interpretation of an analysis may depend on who was included and how unavailable observations were treated.

The efficacy sets are stated as 8 for infiltration and 9 for instillation. The safety at-risk counts are 8 and 10, respectively. The registry does not report a full participant-flow account or define the analysis populations beyond those descriptions. Without that information, it is not possible to determine how participants moved from enrollment to each analysis set or whether exclusions could affect comparisons.

11. 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 serious adverse event listing reports 0 affected among 8 participants at risk in the infiltration group and 0 affected among 10 participants at risk in the instillation group. The listing also reports 0 other adverse events among 8 and 10 participants at risk, respectively. These are the counts displayed in the registry; they should be read with their stated at-risk populations rather than as evidence about participants outside those populations.

A zero count in a small study does not establish that an event cannot occur or that the groups have identical safety profiles. In general, the precision of an event-rate estimate depends on the number of participants observed and the amount of follow-up. The registry record does not report uncertainty intervals for these counts, follow-up duration for safety, or detailed definitions and collection procedures for adverse events.

The primary endpoint efficacy populations differ from the listed safety populations: 8 and 9 for efficacy, and 8 and 10 at risk for safety. The registry does not explain the difference. Death counts are not reported in the registry record, and the top serious-event terms list is empty. These entries do not provide a comprehensive narrative of all safety monitoring or establish that no unlisted event occurred. They describe the serious and other event counts reported in the registry.

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

This record documents a completed Phase 4 study comparing two ways of administering EXPAREL during bilateral augmentation mammoplasty. Its primary question is framed around duration from the end of surgery to the first postsurgical opioid administration. The study enrolled 19 participants and reported efficacy populations of 8 for infiltration and 9 for instillation, with substantial censoring in both groups as described in the registry.

The information in the record does not report the primary outcome estimates, uncertainty intervals, or a statistical test. It therefore does not show how long participants in either group went before a first opioid administration, how large any group difference was, or how precisely such a difference was estimated. The outcome counts of censored and event-observed participants do not answer those questions by themselves.

The study design also limits what a group comparison can establish. The groups were non-randomized and sequential, and the record says they are not a like-for-like control comparison. An observed difference could reflect the administration technique, differences between participants or periods, or other factors that the registry does not describe. The record does not report adjustment for potential confounding.

This study should not be read as establishing that one technique is better, equivalent, or worse than the other. It also does not compare EXPAREL with no EXPAREL or with another analgesic intervention. The listed secondary outcomes are questions measured in the study, not results in themselves. Likewise, the safety counts report no affected participants in the listed groups, but they do not establish the absence of risk or fully characterize safety.

In general, a study can contribute useful descriptive information even when it does not provide a precise or causal comparison. Here, the registry helps identify the intervention techniques, primary endpoint, participant populations, and some event counts. The limits of the posted information mean that broader conclusions require results and methods that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a time-to-event primary endpoint with a non-randomized, sequential comparison. Each feature affects how the results should be read. Time to first opioid administration is a defined event measure, but the registry reports that many participants were censored. A meaningful interpretation therefore depends on event timing, censoring rules, and an analysis method, none of which is fully.

The design also highlights the distinction between comparing observed groups and estimating a causal effect. The study compares infiltration with instillation, but allocation was non-randomized and the record cautions that the arms are not a like-for-like control comparison. An apparent group difference in a table or plot cannot by itself separate the technique from other possible group differences. Statistical adjustment can sometimes address measured differences, but the registry does not report whether such adjustment was used, and adjustment cannot automatically remove all sources of bias.

The mismatch between stated analysis populations is another practical reporting issue. The primary efficacy sets contain 8 and 9 subjects, while the safety at-risk counts are 8 and 10. Clear definitions of analysis populations and participant flow help readers understand which observations contribute to each result. The registry record does not provide that reconciliation.

Finally, the record lists several outcome measures but no analyses. This illustrates why outcome definitions and result reporting are distinct: naming a measure does not establish that a comparison was performed or show its uncertainty. For biostatisticians and clinical researchers, the study is a useful example of why design, endpoint handling, analysis populations, and transparent reporting all matter alongside numerical summaries.

14. 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 gives limited information for assessing the primary comparison. It identifies the endpoint and describes censored counts, but does not report group estimates, uncertainty intervals, test results, or an analysis method. It also does not report the rules used to define censoring, how censoring was handled, or whether sensitivity analyses were conducted.

Non-randomized sequential allocation limits causal interpretation. The registry does not explain how participants were assigned to the groups, whether the groups differed in baseline characteristics, or whether the analysis accounted for potential confounding. The open-label design is listed as having no masking, but the record does not describe outcome assessment procedures or decisions leading to opioid administration.

The stated populations are not fully reconciled. Enrollment was 19; the primary efficacy sets were 8 and 9; and safety at-risk counts were 8 and 10. The registry does not provide participant flow or explain the difference between these sets. It does not report other missing-data details or the completeness of follow-up.

The record lists 8 outcome measures and 0 analyses, but does not report a multiplicity strategy, the analysis plan, or the trial’s own sample-size justification. The sample-size section is a planning illustration based on an observed effect, not the trial’s design. The registry also does not report the duration of safety follow-up or detailed adverse-event collection procedures. Together, these omissions restrict assessment of statistical precision, bias, and the scope of conclusions that can be drawn from the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of EXPAREL in Patients Undergoing Breast Augmentation — NCT01582490.
• Registry record last updated 2014-07-02; status last verified 2014-05.
• Results first posted 2014-07-02.
• 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.

18. Record Summary

This completed Phase 4 study examined EXPAREL administered by instillation or infiltration in subjects undergoing bilateral augmentation mammoplasty. It was prospective, open-label, non-randomized, and sequential. The primary outcome was duration of analgesia, defined as time from the end of surgery to the first postsurgical opioid administration.

The record lists enrollment of 19 and describes efficacy sets of 8 for infiltration and 9 for instillation. It reports 5 and 7 censored participants, respectively. Safety at-risk counts were 8 and 10, with 0 serious adverse events reported in either group. The registry lists 8 outcome measures and 0 analyses.

Group estimates and inferential results for the primary endpoint are not reported in the registry record. The non-randomized design, censoring, and unexplained differences between analysis populations limit interpretation of any group comparison.