Exparel and Marcaine for Pain Management in Thoracoscopic Lobectomy Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exparel and Marcaine for Pain Management in Thoracoscopic Lobectomy Patients (NCT03682224), a randomized phase 3 study. The primary outcome is Total Morphine Equivalents Consumed.

2. Clinical Question

The clinical question concerns postoperative pain management and opioid use following thoracoscopic lobectomy. The study description says participants were followed during the hospital stay and for one year thereafter. Pain was to be assessed using a visual scale, opioid use measured during the postoperative period and at later visits, and drug-related toxicity and other conditions monitored. The primary posted outcome is narrower than that overall set of aims: it is opioid consumption, expressed in morphine equivalents, up to 72 hours after surgery. The registry record does not report the specific population included in the primary outcome analysis or explain how the visual pain scale and later follow-up measures were analyzed.

3. Trial Design

This was a Phase 3, randomized, single-blind, parallel-group trial sponsored by Southern Illinois University. The registry lists an enrollment of 57 and a completed status. The recorded start date is 2018-07-05, and the primary completion date is 2022-09-03. The trial compared two intra-operative local anesthetics in patients undergoing video-assisted thoracoscopic lobectomy: liposomal bupivacaine (Exparel) and bupivacaine-epinephrine (Marcaine).

Randomization indicates that allocation was intended to be determined by chance, but the method used to generate the allocation sequence and the method used to conceal it are not reported in the registry record. The record labels the study single-blind but does not identify who was blinded or explain how blinding was maintained. It also does not report whether participants, clinicians, outcome assessors, or analysts were masked. The arm descriptions are blank, so details beyond the intervention names and the descriptions in the brief summary are not available in the registry record.

The primary outcome is total morphine equivalents consumed, with a timeframe of up to 72 hours after surgery. The registry gives a median and interquartile range as the outcome summary type. The posted arm values are based on 26.0 participants in the Exparel group and 24.0 in the Marcaine group. The registry enrollment figure and the outcome-specific group sizes describe different record fields; the reason for their difference is not reported in the registry record.

The brief summary describes additional planned observations, including pain scores, opioid use after discharge, costs, mortality, and monitoring for toxicity and other conditions. The registry lists VAS Pain Score, Treatment Cost, Pharmacy Cost, and Mortality as secondary outcomes. Details of the secondary-outcome analysis and the handling of follow-up 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 Total Morphine Equivalents Consumed, measured over up to 72 hours post surgery.

The primary endpoint is total morphine equivalents consumed up to 72 hours after surgery. It represents the overall intake of opioid-class drugs converted to a common morphine-equivalent measure. Expressing different opioid medicines in a shared unit is intended to make their combined use interpretable as one quantity rather than as separate drug-specific doses. The registry describes the measure as overall intake of any drugs in the opioid class.

The endpoint is relevant to the stated study aim because opioid use was one of the outcomes the study sought to assess alongside pain management. It is not a direct measure of pain intensity: the registry lists VAS Pain Score separately as a secondary outcome. Nor does opioid consumption alone describe all aspects of recovery or the reasons a patient received a particular amount of medication. The registry record does not report details such as the conversion procedure, whether all sources of opioid use were captured, or how medication use after discharge was handled for this primary endpoint.

The outcome summary is a median with interquartile range. The posted median is 48.0 MEq for Exparel and 42.7 MEq for Marcaine. The recorded lower and upper values are 23.0 and 71.0 for Exparel, and 28.4 and 55.5 for Marcaine. These values describe the observed distributions as posted; they do not by themselves establish whether the groups differ statistically or clinically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison and posts a median and interquartile range for the primary outcome. It does not report the statistical analysis used for the comparison. The explanations below distinguish the posted descriptive summaries from general statistical concepts and from planning assumptions recorded for sample-size illustrations.

What does the median describe?

General: the median is the central value when observations are ordered. It can describe a typical observation without requiring the outcome distribution to be symmetric. Here, the posted medians are 48.0 MEq for Exparel and 42.7 MEq for Marcaine. A median is not an average treatment effect, and comparing two medians does not provide a test of whether the groups differ.

What does the interquartile range describe?

General: the interquartile range describes the middle portion of an outcome distribution by using its lower and upper quartiles. It helps convey variability, but it is not a confidence interval for the group median or for a treatment contrast. The registry labels the primary outcome dispersion as interquartile range and posts lower and upper values of 23.0 and 71.0 for Exparel, and 28.4 and 55.5 for Marcaine. The record does not provide a separate confidence interval for either group summary.

What is needed to assess a group contrast?

General: an inferential comparison estimates how much an outcome differs between groups and how uncertain that estimate is. A confidence interval communicates a range of values compatible with the data and the assumptions of the analysis. A p-value addresses a particular statistical hypothesis under a specified model. Neither statistic is reported for the primary comparison in the registry record. The posted group summaries alone cannot establish whether a contrast is statistically distinguishable from chance variation.

What does randomization contribute?

General: random allocation is intended to reduce systematic differences between groups at the start of a trial, on average. It does not guarantee that groups are identical in every characteristic, especially in a study with limited group sizes. It also does not determine how outcome data should be analyzed. The record labels this trial randomized but does not report the sequence-generation method, allocation concealment, baseline characteristics, or analysis population. The analysis approach and any adjustment for baseline factors are not reported in the registry record.

Why can opioid-use data require care?

General: clinical consumption outcomes can have uneven distributions, with some observations substantially higher or lower than others. A median and interquartile range can be useful descriptive summaries in that setting. General: over-dispersion means that observed variability is greater than a model assumes; if a model does not account for that variability, its uncertainty estimates can be too narrow. The registry does not report a distributional assessment, a model for the outcome, or whether over-dispersion was considered. No particular distribution or modeling approach should therefore be attributed to this trial.

What do the planning assumptions mean?

The registry's sample-size assumptions describe planning illustrations based on the observed effect, rather than the trial's own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between the groups, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. These assumptions describe how a planning illustration is framed, not the analysis performed in the trial. Any sample sizes generated from such assumptions are planning illustrations, not observed power and not evidence that the trial was designed to detect those effects. A trial's observed power should not be inferred from a non-significant result or from a planning calculation.

The record does not report a prospective sample-size justification, the effect size used in the original design, an interim-analysis plan, a stopping rule, or a statistical analysis plan. The planning assumptions recorded for illustrations do not fill those gaps. The registry lists 0 analyses, so no sponsor-reported inferential analysis of the primary endpoint is available in the record.

How should the posted summaries be used?

They can be read as descriptive evidence about the recorded median opioid consumption and its spread in each randomized group. They cannot substitute for a prespecified between-group estimate with an uncertainty measure. General: interpretation of a randomized comparison also depends on how missing data, protocol deviations, and outcome measurement are handled. Those details are not reported in the registry record. The record does not report a recalculated inferential result, and no independent numerical comparison should be inferred from the group summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists VAS Pain Score, Treatment Cost, Pharmacy Cost, and Mortality as secondary outcomes, in addition to the primary opioid-consumption endpoint. The brief summary also describes follow-up assessments and monitoring. When several outcomes are analyzed, the chance of at least one apparently positive result can increase if each is tested separately without accounting for the number of tests. General: multiplicity procedures can control or otherwise address that issue, but the appropriate approach depends on the study's prespecified aims and analysis plan.

A multiplicity strategy, hierarchy of outcomes, or adjustment for multiple testing is not reported in the registry record. The record lists 0 analyses, so it does not provide secondary-outcome test results or a documented approach to interpreting multiple comparisons. The existence of several listed outcomes should not be taken to mean that they were all analyzed in a particular way.

The primary outcome population field is blank. The registry posts outcome group sizes, but does not report whether the primary analysis used all randomized participants, only participants with observed outcome data, or another analysis population. It also does not describe missing-data amounts, reasons for missingness, imputation, sensitivity analyses, or how incomplete follow-up was handled. Those details are not reported in the registry record.

General: missing outcome data can affect both the estimate and its uncertainty, particularly when the reasons for missingness are related to treatment or outcome. Without a description of missingness and the analysis population, the degree to which the posted summaries represent all randomized participants cannot be assessed. The registry record does not provide enough information to determine how missingness or multiplicity may affect interpretation.

11. 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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: prolonged air leak (30.8%), pneumothorax (25.0%), atrial fibrillation/other arrhythmia (12.5%), infection (7.7%).

The registry reports serious adverse events and other adverse events separately. For serious adverse events, it records 12 participants affected among 26 at risk in the Exparel group and 9 among 24 at risk in the Marcaine group. For other adverse events, it records 2 among 26 at risk for Exparel and 1 among 24 at risk for Marcaine. The record reports 0 deaths in each group.

These are descriptive counts. They do not, by themselves, establish whether the groups differ in safety. The registry does not report a statistical comparison, confidence interval, or detailed definition of the adverse-event categories in the posted results. The reason for the difference between overall enrollment and the safety denominators is not reported in the registry record.

The record lists prolonged air leak (30.8%), pneumothorax (25.0%), atrial fibrillation/other arrhythmia (12.5%), and infection (7.7%) among the top serious-event terms. It does not provide term-specific group counts or the denominators used for these percentages. These terms therefore should not be assigned to one treatment group or treated as direct comparative rates. Adverse-event summaries are not equivalent to an assessment of causality, and the registry record does not report whether events were judged related to either study drug.

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

The posted result establishes that the registry contains median opioid-consumption values for both randomized groups, with the outcome defined as total morphine equivalents consumed up to 72 hours after surgery. It also provides the group-specific outcome sizes and the recorded lower and upper values associated with the interquartile-range summary. Those are useful descriptive details about the trial result.

The result does not establish whether Exparel and Marcaine differ statistically. The registry record does not report a between-group estimate, confidence interval, p-value, or analysis method. It also does not report a prespecified criterion for deciding that one treatment is superior, equivalent, or non-inferior. The medians alone cannot answer those questions, and no conclusion about the clinical importance of a possible difference can be drawn from them without further context.

The endpoint is opioid consumption, not pain intensity itself. The registry lists VAS Pain Score as a secondary outcome, but a result for that measure is not included in the registry entries. The record also lists treatment cost, pharmacy cost, and mortality as secondary outcomes without presenting their results. The brief summary describes longer follow-up and monitoring, but the registry information does not provide enough detail to interpret those outcomes.

The safety counts indicate that adverse events were recorded in both groups, with no deaths reported. The available summary does not establish whether the events were caused by treatment, nor does it support a precise comparative safety estimate. Term percentages lack reported denominators and group attribution.

More broadly, the registry record does not describe the analysis population, missing-data handling, randomization procedure, masking details, or statistical plan. These omissions limit the interpretation of both efficacy-related outcomes and safety. The completed status and posted medians are not substitutes for a documented inferential analysis. The result should be understood as a set of descriptive registry findings rather than as a definitive test of a treatment claim.

13. Why This Trial Matters Statistically

This trial addresses a practical statistical challenge: comparing an opioid-consumption outcome between randomized groups while preserving the distinction between descriptive summaries and inferential conclusions. The primary measure combines opioid-class medication use in morphine equivalents, while the posted summary uses medians and interquartile ranges. That choice makes the form of the outcome summary visible, but it does not itself answer whether the groups differ or how precisely a contrast is estimated.

For clinical researchers, the record illustrates why an outcome definition and its analysis need to be read together. The endpoint is specified as total morphine equivalents through 72 hours after surgery, yet the conversion method, analysis population, missing-data approach, and comparison method are not reported in the registry record. Such details shape what a numerical summary means and whether it can be compared fairly across randomized groups.

The trial also includes outcomes beyond opioid use, including pain scores, costs, pharmacy costs, and mortality. Considering multiple outcomes raises questions about prespecification and multiplicity. The registry record does not report how those questions were handled, and it lists 0 analyses. The posted summaries therefore offer less inferential information than a complete results report with estimates, uncertainty intervals, and an analysis plan would provide.

Finally, the safety information shows why counts and percentages require context. Counts need denominators and clear group attribution; term-specific percentages need their underlying event definitions and denominators to support comparison. The record gives some group-level adverse-event counts but does not provide all of that context for the listed serious-event terms. This trial is statistically instructive because it makes clear that randomization and numerical outcome summaries are important, but that interpretation also depends on transparent reporting of analysis, uncertainty, and missingness.

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 does not report the method used to generate the randomization sequence or conceal allocation. Although the study is labeled single-blind, the identity of the masked parties and the procedures used to maintain blinding are not reported. The arm descriptions are blank, and detailed treatment-administration procedures beyond the brief summary are not reported in the registry record.

The primary outcome has descriptive results but no reported inferential analysis. The record lists 0 analyses and does not provide a between-group effect estimate, confidence interval, p-value, or statistical model. It also does not report a prospective sample-size justification, interim analyses, stopping rules, or a full statistical analysis plan. The recorded planning assumptions describe illustrations rather than the trial's own design.

The outcome-specific group sizes differ from the registry enrollment figure, but the reason is not reported in the registry record. The primary outcome population is not specified. Information about missing measurements, withdrawals, protocol deviations, imputation, and sensitivity analyses is also not reported. These gaps limit assessment of how representative the posted outcome summaries are of all randomized participants.

The registry lists four secondary outcomes but does not provide their results in the registry entries. It does not report how multiple outcomes were handled or whether analyses were prespecified. Safety reporting includes group-level counts, but the term-specific serious-event percentages lack reported denominators and group attribution. The record does not explain whether adverse events were judged related to treatment.

Finally, the registry identifies the population as patients undergoing elective thoracoscopic lobectomy and lists lung cancer conditions, but detailed eligibility criteria and baseline characteristics are not reported. The extent to which the results apply to other populations or procedures cannot be assessed from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Exparel and Marcaine for Pain Management in Thoracoscopic Lobectomy Patients — NCT03682224.
• Registry record last updated 2023-01-12; status last verified 2022-12.
• Results first posted 2023-01-12.
• 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

NCT03682224 is a completed Phase 3, randomized, single-blind, parallel-group trial sponsored by Southern Illinois University. It compared intra-operative Exparel, or liposomal bupivacaine, with Marcaine, or bupivacaine-epinephrine, for pain management in patients undergoing video-assisted thoracoscopic lobectomy. The registry lists enrollment of 57, a start date of 2018-07-05, and a primary completion date of 2022-09-03.

The primary endpoint is total morphine equivalents consumed up to 72 hours after surgery. The posted medians are 48.0 MEq for Exparel and 42.7 MEq for Marcaine. The record identifies the summary as median with interquartile range but does not report an inferential comparison, confidence interval, or analysis method. It lists VAS Pain Score, Treatment Cost, Pharmacy Cost, and Mortality as secondary outcomes. The registry also reports adverse-event counts and 0 deaths in each group, with limited detail for the listed serious-event terms.