A Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief (NCT03514277), a randomized phase 4 study. The primary outcome is Mean Postoperative Pain Score.

2. Clinical Question

The clinical question was whether postoperative pain scores differed across the three local-infiltration approaches. The registry describes the purpose as collecting information about how patients feel when pain is managed with the combination or either drug alone. It also lists opioid consumption during the hospital stay, time to achieve physical therapy discharge, and opioid-related adverse events as secondary outcomes. The record does not post results for those secondary outcomes. Enrollment was 19, and the study status is terminated. The registry does not state why the study was terminated or provide a conclusion about which approach produced better pain relief.

3. Trial Design

The registry describes a prospective, randomized, double-masked, parallel-group study and identifies it as phase 4. Its official title specifies posterior lumbar spine surgery and compares combined bupivacaine and EXPAREL with either drug alone for postoperative analgesia. Three intervention groups are listed: local infiltration of EXPAREL and bupivacaine, local infiltration of EXPAREL, and local infiltration of bupivacaine. The registry does not report the randomization procedure, allocation ratio, or masking procedures.

Enrollment is listed as 19. The record gives a study start date of 2016-12-01 and a primary completion date of 2019-12-31. The study status is terminated. The reason for termination, recruitment progress, and whether the planned enrollment was reached are not reported in the registry record. A planned sample size and its justification are also not reported in the registry record.

The posted primary endpoint summaries include 10 participants in the combination group and 4 in each single-drug group. The primary endpoint description notes that data were not collected for one patient in the combination group. Safety counts use groups at risk of 11, 4, and 4, respectively. These are distinct posted counts for different reported measures; the record does not explain the difference between the combination group's safety count and its primary endpoint count.

Three secondary outcomes are named: total opioid consumption during the hospital stay, mean time to achieve physical therapy discharge, and the number of participants with opioid-related adverse events. The registry lists four outcome measures overall, but posts no analyses. The timing and methods for collecting the secondary measures, as well as any prespecified statistical analysis plan, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data is not collected for one patient in the Local infiltration of EXPAREL and Bupivacaine group

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 Mean Postoperative Pain Score, measured over last day of hospitalization, average of 3 days in hospital.

The primary endpoint is mean postoperative pain score on the Wong-Baker pain faces scale. The scale is described as running from 0 for no pain to 10 for extreme pain. A pain score provides a patient-reported measure of the symptom the study intended to address, rather than a measure of opioid use or functional recovery. The registry identifies the measure as a mean and gives the full range for each group.

The timeframe is described as the last day of hospitalization, with an average of 3 days in hospital. The wording does not clarify how scores from different hospital days were combined or exactly how the average was formed. Additional details about the timing of each assessment and the handling of repeated scores are not reported in the registry record.

The posted means are 5.2 for the combination group, 4.2 for EXPAREL alone, and 5.6 for bupivacaine alone. The corresponding full ranges are 3.0 to 7.6, 3.1 to 5.6, and 4.4 to 6.7. These summaries describe the observed scores, but they do not provide an estimate of uncertainty around each mean or a statistical test of group differences. The record does not explain what difference in pain score would be considered important to patients or clinicians.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, double-masked, and parallel-group. In general, randomization is intended to reduce systematic differences between assigned groups at the start of a trial. A parallel-group design assigns participants to one study group, with each group receiving a different intervention. Masking is intended to limit the influence of knowledge about assignment on care, outcome assessment, or reporting. These are general statistical concepts; the registry does not describe its specific randomization or masking procedures.

What the mean describes

The primary endpoint is a mean pain score for each group. In general, a mean is a measure of the center of observed values: it adds information about the group’s average recorded score, but does not describe every participant’s experience. The reported values are 5.2 for the combination group, 4.2 for EXPAREL alone, and 5.6 for bupivacaine alone. The registry gives the full range for each group rather than a standard deviation or another measure of variability.

A full range identifies the lowest and highest recorded values in a group, as reported in the registry. The ranges are 3.0 to 7.6 for the combination group, 3.1 to 5.6 for EXPAREL alone, and 4.4 to 6.7 for bupivacaine alone. A range describes the extremes of the observed scores and can be sensitive to individual observations. It is not a confidence interval. In general, a confidence interval describes statistical uncertainty around an estimated quantity under a specified method; no confidence intervals for the group means or comparisons are posted in the registry record.

What is missing from an inferential comparison

In general, an inferential comparison estimates how much outcomes differ between groups and how uncertain that estimate is. A statistical test may also assess compatibility with a stated null hypothesis. Those methods depend on an analysis plan and assumptions about the data. The registry record does not post a primary comparison, an effect estimate, a confidence interval, or a p-value. It also does not report an adjustment for baseline variables or other covariates. The descriptive means should therefore not be treated as estimates from an adjusted analysis or as evidence from a reported hypothesis test.

The study has three groups, so a statistical plan could address an overall comparison, selected pairwise comparisons, or another prespecified question. Which approach was planned is not reported in the registry record. The groups' unequal observed endpoint counts also matter for estimating uncertainty and choosing an analysis method. No method for handling repeated pain measurements, departures from distributional assumptions, or any other features of the outcome is posted.

Why sample size and precision are different

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to be detected, variability, significance level, allocation, and analysis. It does not describe the precision actually achieved. A power calculation made after observing results is not a measure of observed power and cannot replace an estimate with an uncertainty interval. The registry includes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Those assumptions describe the illustration, not the trial's original design. Its numerical planning results are not reported in the registry record. The trial's own sample-size justification is also not reported in the registry record.

The posted observed group counts are 10, 4, and 4 for the primary endpoint, while total enrollment is 19. The record says one patient in the combination group did not have primary outcome data. It does not report a protocol-defined analysis population, an intention-to-treat analysis, a per-protocol analysis, or the statistical method used for missing data. Consequently, the summaries alone do not establish how all randomized participants were treated in the analysis.

Interpreting the safety counts

Safety summaries use groups at risk of 11 for the combination, 4 for EXPAREL, and 4 for bupivacaine. The serious adverse event counts are zero in each group. In general, counts describe the number of recorded events or participants with events according to the registry's reporting convention; the convention used for these figures is not further explained. Counts without comparative estimates or uncertainty measures do not establish that risks are the same. They also do not establish that any event was caused by a study drug.

The registry lists no analyses and reports no statistical plan, interim analyses, or multiplicity procedure. The absence of posted analyses means the record does not support claims about statistical significance or precision. General statistical explanations do not fill these gaps: the specific analysis methods used for this trial are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary mean postoperative pain score and three secondary outcomes. The secondary outcomes are total opioid consumption during the hospital stay, mean time to achieve physical therapy discharge, and the number of participants with opioid-related adverse events. Results for those secondary outcomes are not posted. The registry also lists zero analyses, so there are no reported inferential results across the listed outcomes.

When a study evaluates more than one outcome or multiple group comparisons, the chance of at least one apparently unusual result can depend on how many tests are conducted and how they are selected. In general, a multiplicity plan specifies whether and how statistical inference will account for multiple comparisons. The registry does not report a multiplicity adjustment or a hierarchy for testing the primary and secondary outcomes. It is therefore not possible to determine whether any planned control of multiple testing was intended.

The primary outcome description states that data were not collected for one patient in the combination group. The endpoint counts are 10, 4, and 4 across the three groups. A missing-data method, reasons for missingness, and sensitivity analyses are not reported in the registry record. The record also does not identify the analysis population or say how participants who were randomized but lacked outcome data were handled.

The registry's overall enrollment is 19, while the posted primary endpoint counts cover 10, 4, and 4 participants. Safety counts at risk are 11, 4, and 4. The registry does not explain these count differences. Details of planned interim analyses, stopping criteria, and any statistical analysis plan are not reported in the registry record. The terminated status alone does not identify whether missingness, multiplicity, or any analysis decision influenced the study's course.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts of 0 among 11 participants at risk in the combination group, 0 among 4 at risk in the EXPAREL group, and 0 among 4 at risk in the bupivacaine group. It reports no deaths in any of the three groups. These are counts as posted; they do not establish that the interventions have identical safety profiles or that serious events could not occur.

For other adverse events, the registry reports 1 among 11 at risk in the combination group, 0 among 4 at risk in the EXPAREL group, and 1 among 4 at risk in the bupivacaine group. The terms for those events are not specified in the posted summary. No serious adverse event terms are listed. The record does not report statistical comparisons, uncertainty intervals, or an assessment of whether an event was related to an intervention.

These safety counts use 11 participants at risk in the combination group, whereas the primary endpoint summary includes 10 participants in that group and notes one patient without collected outcome data. The registry does not explain the distinction. Event counts from a small study are descriptive and do not provide a precise estimate of uncommon harms. The reported numbers should be read as the safety information recorded in this study, not as a complete characterization of risk.

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

The registry record supports a limited descriptive account of pain scores in three randomized groups. The posted means are 5.2 for local infiltration of EXPAREL and bupivacaine, 4.2 for EXPAREL alone, and 5.6 for bupivacaine alone. The ranges report the spread from the lowest to the highest observed score in each group. The record does not report a statistical comparison, confidence interval, or p-value for these results.

Accordingly, the summaries do not show whether the observed group means differ beyond what could arise from sampling variation. They do not establish the size or precision of a comparative effect, and they do not identify a preferred approach. The registry gives no threshold for interpreting the clinical importance of a score difference. No conclusion about clinical importance can be made from the listed summaries alone.

The primary endpoint counts are small and unequal: 10 in the combination group and 4 in each single-drug group. One patient in the combination group had no collected primary endpoint data. The posted results do not explain how missing data were handled or identify the analysis population. The safety count for the combination group is 11 at risk, and the reason it differs from the endpoint count is not reported in the registry record.

The record also does not post the three named secondary outcomes, which concern opioid consumption, physical therapy discharge timing, and opioid-related adverse events. It therefore cannot answer those questions from the results listed. Serious adverse event counts are zero in all groups, but those counts are not evidence that the groups have the same safety profile.

The study status is terminated, but the reason is not reported in the registry record. Termination by itself does not establish whether results influenced the decision, whether the planned enrollment was reached, or whether the study met its original objectives. Overall, the record offers a small set of descriptive outcome and safety figures, not a complete comparative analysis of the interventions.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a randomized design and a reported statistical result. Randomization can support a fair comparison when it is implemented and analyzed appropriately, but the registry's design label does not substitute for a posted estimate of the group contrast or its uncertainty. Here, the primary endpoint is reported by group as means and full ranges, with no inferential comparison.

The three-arm structure makes clarity about the statistical question especially important. A comparison could focus on the combination against each single-drug approach, or on a broader question across all groups. The registry does not state which comparisons were prespecified or how multiplicity was addressed. Without that information, readers cannot determine which claims the study was designed to evaluate or how results were intended to be interpreted.

The endpoint counts also demonstrate why outcome completeness and analysis populations matter. The combination group has 10 participants in the primary summary, and the record notes one participant without collected data; the safety summary lists 11 at risk. The registry does not explain the count distinction or missing-data handling. Reporting these details is important because the analyzed participants and the method used for incomplete outcomes can affect both estimates and their precision.

Finally, descriptive safety counts and a terminated status have limited meaning without context. Zero serious adverse events were recorded in each group, but the counts are not comparative risk estimates. The registry does not explain the termination or provide the secondary outcome results. This record therefore offers a useful example of how a trial's registration and posted summaries can document its question and some observations while leaving important elements of statistical interpretation unresolved.

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 does not post an inferential analysis for the primary endpoint or results for the named secondary outcomes. There are no reported comparison estimates, confidence intervals, p-values, or adjusted analyses. This prevents assessment of the precision of between-group differences and leaves the descriptive summaries without a formal comparative interpretation.

The primary endpoint counts are 10, 4, and 4 across the three arms, and the record identifies one patient in the combination group without collected outcome data. The registry does not describe the analysis population, the handling of missing values, or reasons for missingness. The safety count at risk for the combination group is 11, and the record does not explain how this relates to the primary endpoint count.

Further trial details that would help interpretation are not reported in the registry record. These include a sample-size justification, allocation procedure, masking procedures, outcome assessment schedule beyond the stated timeframe, and the statistical analysis plan. The record does not describe a multiplicity strategy or any interim analyses. The wording of the endpoint timeframe—last day of hospitalization, average of 3 days in hospital—does not fully specify how pain measurements were combined.

Enrollment is listed as 19 and the study status is terminated, but the reason for termination and whether planned enrollment was reached are not reported in the registry record. Safety summaries give counts without event-term detail for the other adverse events, comparative analyses, or assessments of relatedness. These limitations mean the posted record cannot support a complete assessment of efficacy, safety, or the reasons the study ended.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief — NCT03514277.
• Registry record last updated 2021-01-06; status last verified 2020-12.
• Results first posted 2021-01-06.
• 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

NCT03514277 is a phase 4, prospective randomized, double-masked, parallel-group study of local infiltration for postoperative analgesia in posterior lumbar spine surgery. The three groups received EXPAREL with bupivacaine, EXPAREL alone, or bupivacaine alone. Enrollment is listed as 19. The study started on 2016-12-01, has a primary completion date of 2019-12-31, and is recorded as terminated.

The primary endpoint is mean postoperative Wong-Baker pain score, described on a scale from 0 for no pain to 10 for extreme pain. The posted group means are 5.2, 4.2, and 5.6, with full ranges of 3.0 to 7.6, 3.1 to 5.6, and 4.4 to 6.7. One patient in the combination group had no collected primary endpoint data. The record lists three secondary outcomes but posts no results for them and no statistical analyses. The reason for termination and the trial's statistical analysis plan are not reported in the registry record.