Mixture of Liposomal Bupivacaine and Bupivacaine for TAP Block for Open Hysterectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mixture of Liposomal Bupivacaine and Bupivacaine for TAP Block for Open Hysterectomy (NCT03250507), a randomized phase 4 study. The primary outcome is Total Opioid Consumption During the First 72 Hours Postoperatively as Measured in Morphine Equivalents (mg).

2. Clinical Question

3. Trial Design

The registry identifies NCT03250507 as a completed, randomized, quadruple-masked, parallel-group phase 4 trial sponsored by Henry Ford Health System. Its enrollment is listed as 90. The study concerns patients having open abdominal hysterectomy and evaluates different bupivacaine formulations delivered by TAP block. The registry record does not describe the method used to generate the random sequence, allocation concealment, or which people were included in the masking designation.

The three described regimens were 60 mL 0.25% bupivacaine alone; 20 mL liposomal bupivacaine with 40 mL saline; and a mixture of 20 mL liposomal bupivacaine with 40 mL 0.25% bupivacaine. These descriptions specify the intended study regimens. The primary outcome reports results for 18 participants in the bupivacaine group, 20 in the liposomal bupivacaine group, and 19 in the combination group. The registry does not explain the difference between these outcome counts and the overall enrollment.

The primary endpoint is total opioid consumption in morphine equivalents over 0–72 hours postoperatively, summarized by median and interquartile range. Secondary outcomes listed in the registry include patient satisfaction, hospital length of stay, local anesthetic toxicity, hypotension, and visual analogue pain scores. Posted results are available for satisfaction and hypotension; the other listed secondary outcomes are not reported in the registry record. The registry record does not report a detailed statistical analysis plan, eligibility criteria, or the analysis population definition.

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.

Population: 13 patients were excluded from study analysis due to meeting exclusion criteria. N=25 in group Bupi, N = 27 in group Liposomal bupi, and N=25 in group liposomal bupi and bupi. 20 patients were discharged within 72 hr. Data is given for those in the hospital for 24 hr periods. For the period 24-48 hr, n = 24 in group bupivacaine, n = 26 in group liposomal, n = 25 in group mixture. For the period 48-72 hr, n = 18 for group bupivacaine, n = 20 for group liposomal, and n = 19 for group mixture. \*

6. Primary Endpoint

The registry lists the primary outcome as Total Opioid Consumption During the First 72 Hours Postoperatively as Measured in Morphine Equivalents (mg), measured over 0 - 72 hours post-operatively.

The primary endpoint is total opioid consumption during the first 72 hours after surgery, expressed in milligrams of morphine equivalents. Converting opioid use to a common equivalent scale makes consumption across opioid medications expressible in a shared unit. The endpoint captures medication use over a specified postoperative period, rather than a single pain rating at a single assessment.

The registry summarizes consumption using the median and interquartile range. A median describes the midpoint of the observed values when ordered; the interquartile range describes the central spread of those values. This is a useful descriptive approach when a distribution may be asymmetric or include unusually high values, because the median is less affected by extreme observations than the mean. That is a general statistical rationale, not a statement about the actual shape of these trial data; distributional details are not reported in the registry record.

The posted median was 208.0 mg in the bupivacaine group, with an interquartile range from 155.0 to 270.0; 203.0 mg in the liposomal bupivacaine group, from 153.0 to 283.0; and 202.0 mg in the combination group, from 116.0 to 325.0. These summaries describe the observed groups. The registry record does not report a formal primary comparison, an estimate of a between-group effect, or a confidence interval for the primary outcome. Therefore, the medians alone do not establish whether the groups differ beyond sampling variability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the median summarize? The median is the middle value after observations are ordered. It can describe the center of a skewed distribution without allowing a small number of extreme values to pull the estimate as strongly as they might pull a mean. The interquartile range gives the interval between the lower and upper quartiles and describes the spread of the central portion of the observed values. These are general explanations. The posted primary endpoint uses medians and interquartile ranges, but the registry record does not describe the underlying distributions or explain why this summary was chosen.

What can be learned from the primary summaries? The medians are 208.0 mg for bupivacaine, 203.0 mg for liposomal bupivacaine, and 202.0 mg for the mixture. The corresponding interquartile ranges are 155.0 to 270.0, 153.0 to 283.0, and 116.0 to 325.0. These values describe each group separately. A comparison between groups ordinarily requires an effect estimate, an uncertainty interval, and an inferential method appropriate to the outcome and design. Those primary comparison details are not reported in the registry record. Comparing the medians by eye or judging whether the interquartile ranges overlap cannot replace such an analysis.

What does a confidence interval mean? In general, a confidence interval expresses uncertainty around an estimated effect under the assumptions of the analysis method. A wide interval indicates that the data are compatible with a broad range of effects; an interval that includes no difference does not establish that the groups are equivalent. Interpretation depends on the estimate, the interval, the study design, and the analysis plan. The posted secondary risk differences have confidence intervals, but no corresponding inferential interval is reported for the primary endpoint.

How should the unadjusted secondary comparisons be read? The registry posts risk differences and unadjusted p-values for satisfaction and hypotension. A risk difference expresses the difference in observed proportions between a comparison group and the bupivacaine group. A p-value measures how incompatible the observed data are with a specified null model, assuming the model and analysis conditions hold; it does not measure the size or importance of an effect. An unadjusted p-value does not account for the fact that multiple outcomes and comparisons may be considered. No multiplicity procedure is reported in the registry record, so these p-values should be read as exploratory rather than as a complete confirmatory analysis.

Why can over-dispersion matter? In general, over-dispersion occurs when outcome variability exceeds what a statistical model assumes. If ignored, standard errors and confidence intervals can be too optimistic, and hypothesis tests can be poorly calibrated. This is relevant as a general methodological consideration for count or binary outcomes, but the registry record does not report a model, a dispersion assessment, or an over-dispersion adjustment for this trial. It would therefore be inappropriate to claim that a particular method was used or was needed for these data.

What do the planning illustrations represent? The satisfaction comparison includes planning illustrations based on the observed effect, with assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For planning for 100% of the observed effect, the illustrations give 259 participants per arm for 80% power and 345 participants per arm for 90% power. For planning for 75% of the observed effect, they give 455 participants per arm for 80% power and 609 participants per arm for 90% power. For planning for 50% of the observed effect, they give 1,012 participants per arm for 80% power and 1,354 participants per arm for 90% power. These are planning illustrations, not observed power and not evidence that the trial was designed with these assumptions. The registry record does not report the trial's own sample-size justification.

Why are some comparisons absent? The available primary summaries do not support a reported two-arm comparison in the posted analysis, and the registry record contains no reported primary analysis. No recalculated primary contrast is presented. When a sponsor's own analysis is reported, it takes precedence over a simple recalculation from summary statistics; in this case, the registry record lists no reported analyses. The main inferential limitation is therefore not a conflicting recalculation but the absence of a reported primary comparison and its uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes and provides more than one comparison for the outcomes with posted results. When many outcomes or contrasts are examined, the possibility of at least one apparently notable finding by chance can increase. Statistical approaches such as a prespecified hierarchy, adjustment of significance thresholds, or control of a family-wise error rate can address multiplicity, but the registry record does not report whether any such approach was planned or used. The unadjusted secondary p-values should therefore not be interpreted as if they were adjusted confirmatory tests.

The registry record lists no reported analyses. It does not report which outcomes or contrasts were prespecified for inferential testing, whether any interim analyses were planned, or how the primary endpoint was to be analyzed. It also does not report an analysis population definition, such as whether participants were analyzed according to assigned group, or a protocol for handling missing outcome data. These details cannot be inferred from the randomized design or from the posted summary counts.

Outcome counts vary: the primary endpoint reports 18, 20, and 19 participants, while satisfaction and hypotension use different group counts. The adverse-event summaries use 30 participants at risk in each group. These denominators are outcome-specific; the registry record does not explain the differences, identify the reasons for missing values, or state whether any observations were excluded. They should not be added together or treated as a single common analysis population.

Without a reported missing-data strategy, it is not possible to judge whether the observed summaries could be affected by incomplete follow-up or other exclusions. The registry record also does not report sensitivity analyses or methods for addressing missingness. These gaps limit assessment of both the robustness of the primary descriptive results and the confirmatory status of the secondary comparisons.

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.

The registry reports serious adverse events, other adverse events, and deaths separately for the three groups. For each group, 30 participants are listed as at risk; the reported counts of serious adverse events, other adverse events, and deaths are all 0. The record does not list serious adverse event terms.

These figures describe what was posted for the stated safety denominators. A zero count means that no events of that category were recorded in the registry results for that group; it does not prove that the underlying risk is zero. Safety summaries are also limited by the size and duration of observation, and the registry record does not provide additional detail about event collection, follow-up completeness, or adjudication.

The safety denominators differ from those reported for the primary and some secondary outcomes. They should not be assumed to represent the same analysis population. The separate secondary outcome for hypotension is not the same as the broad serious or other adverse-event counts, and its posted group counts should be interpreted as that specific outcome. The registry record does not provide further safety analyses that would permit a more detailed assessment.

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

The posted primary data describe opioid consumption after open abdominal hysterectomy under three TAP block regimens. The group medians range from 202.0 mg to 208.0 mg over the first 72 hours after surgery, and the interquartile ranges show variation among participants within each group. These are descriptive summaries of the posted outcomes, not estimates of a tested difference between regimens.

The registry record does not report a formal primary comparison, a confidence interval for a primary effect, or a primary p-value. Thus, the summaries alone cannot establish whether the observed differences in medians reflect a meaningful between-group difference or sampling variation. They also cannot establish equivalence or rule out differences that the available summaries do not resolve. The record does not report a sample-size justification or primary analysis plan that would help interpret the precision of this endpoint.

The posted secondary comparisons add information about satisfaction and hypotension, but they are unadjusted and do not answer the primary question about opioid consumption. The other listed secondary outcomes are not reported in the registry record. The safety summaries report zero serious adverse events, other adverse events, and deaths in the listed groups, but those counts do not establish that the regimens have no risk.

These results should be understood as a limited registry summary rather than a complete account of all trial analyses. The registry record does not report detailed methods for randomization, missing data, analysis populations, or multiplicity. Without those details and a reported primary inferential analysis, the strongest interpretation is descriptive: the posted group summaries show similar central opioid-consumption values alongside substantial within-group spread, while uncertainty about comparative effects remains unquantified.

13. Why This Trial Matters Statistically

This trial illustrates why a randomized design and descriptive results do not automatically provide a complete comparative analysis. Randomization is intended to support fair comparisons between assigned groups, but interpretation also depends on clear reporting of the outcome analysis, effect estimates, uncertainty, and the population included. Here, the primary endpoint is reported with medians and interquartile ranges, while a formal primary comparison and its uncertainty are not reported in the registry record.

The endpoint choice also matters. Opioid consumption in morphine equivalents captures medication use over a postoperative interval, while satisfaction, pain scores, blood pressure, and hospital stay represent different dimensions of recovery and care. These measures can complement one another, but they are not interchangeable. A reader needs the prespecified analysis plan and results across outcomes to understand how the trial's primary question was addressed.

The posted secondary results demonstrate another general statistical issue: unadjusted comparisons across several outcomes may produce isolated findings that require cautious interpretation. Confidence intervals help show uncertainty, and adjustment strategies can address repeated testing, but neither a multiplicity approach nor a reported analysis plan is available in the registry record. Planning calculations based on an observed effect are also not the same as the trial's original design justification or observed power.

For biostatisticians and clinical researchers, the record is a reminder that outcome-specific denominators, missing-data decisions, analysis populations, and prespecified methods are essential parts of transparent reporting. Without them, even a completed randomized trial can leave readers unable to judge the precision and robustness of its primary comparison.

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.

A central limitation is that the registry record does not report an inferential analysis for the primary opioid-consumption endpoint. The posted medians and interquartile ranges permit description of the groups, but do not quantify the uncertainty in a difference between them. The record also does not report a primary effect estimate, confidence interval, or p-value.

Outcome-specific participant counts vary across the primary endpoint, secondary outcomes, and safety summaries. The registry record does not explain the reasons for those differences or describe missing-data handling, exclusions, or the analysis population. This makes it difficult to assess whether outcome summaries are based on comparable sets of participants or whether missingness could affect interpretation.

The trial includes multiple outcomes and comparisons, but no multiplicity strategy is reported. The secondary comparisons are unadjusted, and the record lists no reported analyses. It is therefore unclear which comparisons were planned for formal inference and how the posted calculations relate to a prespecified plan. Results for hospital length of stay, local anesthetic toxicity, and visual analogue pain scores are not reported in the registry record, limiting the breadth of the available outcome assessment.

Other design and conduct details are also not reported, including the random-sequence generation method, allocation concealment, the roles covered by quadruple masking, detailed eligibility criteria, and the trial's sample-size justification. The planning illustrations based on an observed secondary effect do not address that gap. These registry-reporting limitations do not establish that the underlying trial lacked these methods; they mean only that they are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mixture of Liposomal Bupivacaine and Bupivacaine for TAP Block for Open Hysterectomy — NCT03250507.
• Registry record last updated 2022-12-21; status last verified 2022-11.
• Results first posted 2022-12-21.
• 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.

18. Record Summary

NCT03250507 is a completed randomized, quadruple-masked, parallel-group phase 4 trial sponsored by Henry Ford Health System, with enrollment listed as 90. It evaluates three TAP block regimens for patients having open abdominal hysterectomy: bupivacaine alone, liposomal bupivacaine with saline, and a mixture of liposomal bupivacaine with bupivacaine.

The primary outcome is total opioid consumption in morphine equivalents during 0–72 hours postoperatively, reported as a median and interquartile range for each group. The registry record does not report a formal primary comparison. Posted secondary results include satisfaction and hypotension; the other listed secondary outcomes are not reported in the registry record. Unadjusted secondary comparisons and safety counts are available, but analysis methods, multiplicity handling, and missing-data procedures are not reported.