Evaluation of the Safety and Efficacy of EXPAREL When Administered Into the TAP in Subjects Undergoing Cesarean Section: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Safety and Efficacy of EXPAREL When Administered Into the TAP in Subjects Undergoing Cesarean Section (NCT02353754), a non-randomized phase 4 study. The primary outcome is Total Postsurgical Narcotic Consumption in Morphine Equivalents.

2. Clinical Question

3. Trial Design

This was a Phase 4, multicenter, open-label study with a parallel-group model. The registry record identifies allocation as non-randomized and masking as none. It lists planned enrollment of 12 and describes two groups: Standard of Care and EXPAREL/TAP. The study began in 2015-05, had primary completion listed as 2015-06, and is recorded as terminated. The reason given for termination was slow enrollment.

In the Standard of Care group, participants were to receive intrathecal morphine injection, described as 0.2 mg, in conjunction with single-shot spinal anesthesia, with no TAP block. In the EXPAREL/TAP group, participants were to receive bilateral TAP infiltration with EXPAREL after bupivacaine spinal anesthesia. The registry description specifies the dose and volume, but no participants were enrolled into this group. The actual participant experience therefore consisted only of assignment to the Standard of Care group, according to the record.

These design and enrollment details sharply limit what the study can establish. A planned parallel design does not itself yield a group comparison; observations from both groups are needed for that purpose. Here, the record reports 12 subjects assigned to Group 1 and no subjects enrolled into Group 2. In addition, the design was non-randomized and open-label. Even if both groups had enrolled participants, those features would require caution in interpreting comparisons, because group assignment would not have been randomized and treatment status was not masked. In the actual record, the missing EXPAREL/TAP group means there is no between-group estimate to interpret.

The registry record does not report a detailed recruitment plan, allocation procedure, or statistical analysis plan. It also does not report why enrollment was slow or whether any changes to the design were considered. The study’s multicenter designation does not establish how many sites enrolled participants or how enrollment was distributed across sites; those details 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: The study was terminated due to slow enrollment after 12 subjects were assigned to Group 1 (Standard of Care/Duramorph). As no subjects were enrolled into Group 2 (EXPAREL/TAP), no conclusions can be drawn regarding the study endpoints.

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: The study was terminated due to slow enrollment after 12 subjects were assigned to Group 1 (Standard of Care/Duramorph). As no subjects were enrolled into Group 2 (EXPAREL/TAP), no conclusions can be drawn regarding the study endpoints.

6. Primary Endpoint

The registry lists the primary outcome as Total Postsurgical Narcotic Consumption in Morphine Equivalents, measured over Through 72 hours postdose.

The primary endpoint was total postsurgical narcotic consumption in morphine equivalents, measured through 72 hours postdose. It is a continuous outcome: it represents a quantity of postoperative narcotic use expressed on a common morphine-equivalent scale. Such a measure can be used to describe the amount of rescue narcotic medication taken over a stated observation period and to compare average consumption across groups when both groups have usable outcome data.

The registry lists the endpoint parameter as a mean and its dispersion as a standard deviation. A mean describes the central level of the recorded consumption, while a standard deviation describes how much individual observations vary around that mean. Both are useful for characterizing a continuous endpoint, but neither value is included in the registry record for this study. The registry’s outcome description says that the endpoint data refer to 7 participants who received rescue medication. It does not provide the mean, standard deviation, or a group-specific result in the record.

The outcome has a defined time window, which matters because consumption measured over different periods would not represent the same quantity. It is also important to distinguish the endpoint’s intended role from evidence of a comparison. The endpoint was planned to address postoperative narcotic consumption, but no participants were enrolled into the EXPAREL/TAP group. The available record therefore does not provide a contrast between the planned intervention and comparator. The actual endpoint values and the handling of participants who did not receive rescue medication are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a mean of a continuous measure, with standard deviation as the dispersion measure. This is a conventional way to summarize a quantitative outcome such as total narcotic consumption. The mean gives a central summary across participants, while the standard deviation describes the spread of individual values. These summaries can help readers understand both typical consumption and participant-to-participant variability. In this record, however, the endpoint mean and standard deviation are not reported, so neither the level nor the variability can be characterized from the registry entries.

What a comparison would require

To estimate a difference in mean consumption between the planned groups, outcome data from participants in both groups would be needed, along with a defined analysis approach. The record reports 12 subjects assigned to Standard of Care and no subjects enrolled into EXPAREL/TAP. As a result, there is no observed two-group contrast to estimate. A mean from one group, even if it were reported, could describe that group but could not show how its outcome compares with an unobserved group.

For a comparative estimate, a confidence interval would ordinarily communicate the range of values reasonably compatible with the observed data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, while an interval that includes values on different sides of no difference may leave the direction or size uncertain. These are general explanations of confidence intervals. The registry record does not report a confidence interval for this trial, and the missing EXPAREL/TAP group prevents estimation of a group difference from the reported enrollment.

A p-value is a measure of how compatible observed data are with a specified null hypothesis under a statistical model. It does not measure the probability that the null hypothesis is true, and it does not state the clinical importance of an effect. No p-value or inferential comparison is reported in the registry record. With no participants in the EXPAREL/TAP group, there is no basis in the posted results for interpreting statistical significance of a between-group difference.

Why the allocation design matters

The registry identifies allocation as non-randomized. Random assignment is a design method intended to reduce systematic differences between groups, on average, by making assignment independent of participant characteristics. In a non-randomized study, observed group differences may reflect underlying differences in who entered each group, differences in care, or other factors, as well as any intervention effect. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjustment plan or adjusted results.

The study is also described as open-label, with no masking. In general, knowledge of treatment assignment can influence behavior, co-interventions, reporting, or assessment, depending on the outcome and study conduct. This possibility is a methodological consideration rather than a finding about this trial. The record does not describe outcome-assessor masking, procedures to limit influence, or the measurement process beyond naming the primary endpoint and its timeframe.

How to understand dispersion and distribution

A standard deviation is most informative when considered alongside the outcome distribution and the endpoint’s scale. If a continuous measure is strongly skewed or has unusually variable values, the mean and standard deviation may not fully describe its distribution. Over-dispersion, in general, means that variability is greater than a statistical model expects; accounting for it can affect standard errors and the precision of estimates. These concepts are general. The record does not provide individual observations, distribution summaries, or diagnostic assessments, so no conclusion about skewness or over-dispersion can be made for this endpoint.

The outcome description refers to 7 participants who received rescue medication. It does not clarify how participants without rescue medication were handled in the endpoint analysis, whether the value was zero for such participants, or whether the endpoint summary was restricted to those receiving medication. Those distinctions can change the meaning of a consumption measure. The registry record does not report the analysis population, a missing-data method, or sufficient outcome details to resolve this issue.

Why no recalculated estimate is available

A recalculated, unadjusted estimate would require posted summary statistics suitable for calculation, such as group-specific means and measures of variation for both groups. Those inputs are not reported, and one group enrolled no participants. Consequently, the available record does not support a recalculated group difference, standard error, confidence interval, or p-value. This is not a finding that the groups had equal outcomes; it is a consequence of the absence of a comparative dataset.

The registry gives sample-size assumptions for planning illustrations based on an observed effect, but no observed comparative effect is reported in the registry record for this trial. Any sample-size illustration should be understood as a planning calculation rather than observed power. No participant count for a hypothetical design can substitute for the missing outcome contrast, and the registry record does not report the trial’s own sample-size justification or a detailed power calculation.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Standard of Care")
n   <- c(12)
m   <- c(6.1)
sp  <- c(3.67)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Standard of Care  12  6.100  3.670  3.768  8.432

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and repeats Total Postsurgical Narcotic Consumption in Morphine Equivalents in its secondary-outcome list. It records 0 analyses. The available record does not explain whether the repeated listing reflects distinct assessment times or another distinction, so the endpoint list cannot be used to infer an analysis plan. The registry record does not report a multiplicity procedure, such as a method for controlling the chance of false-positive findings across several endpoints or analyses.

Multiplicity is a general concern when investigators test many outcomes or make many comparisons. As the number of statistical tests grows, the chance of at least one apparently notable result can increase if no adjustment or interpretive plan is used. That general concern does not establish that any particular analysis was performed. The record lists no analyses and no inferential results, so there are no reported tests to evaluate for multiplicity.

Missing-data methods and analysis populations are also not reported in the registry record. The endpoint description says the data refer to 7 participants who received rescue medication, but does not specify how the other assigned participants were handled for that endpoint. It does not say whether all assigned participants were included in an analysis, whether analyses were limited to participants with observed outcomes, or how any missing measurements were addressed. The record does not describe a prespecified analysis population or imputation approach.

These omissions matter because an analysis restricted to participants with observed measurements can differ in meaning from an analysis that includes all assigned participants under a stated missing-data strategy. The available information is insufficient to determine whether missingness affected endpoint summaries. The lack of an enrolled EXPAREL/TAP group is a separate and more fundamental limitation: no missing-data procedure can create observed outcomes for participants who were never enrolled in that arm.

12. 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.

Most frequent non-serious adverse event terms

The registry reports 0 serious adverse events among 12 participants at risk in the Standard of Care group. It reports 2 participants with other adverse events among 12 at risk in that group. These are the posted counts and denominators; they should be read as descriptive safety reporting for the participants enrolled in that arm, not as comparative estimates.

The EXPAREL/TAP group has 0 participants at risk and 0 reported serious or other adverse events. With no participants enrolled, those zeros do not represent observed safety experience after receiving EXPAREL/TAP. They cannot be compared with the Standard of Care counts and do not establish that the intervention has no adverse events.

The registry record does not report deaths. It also does not list serious adverse-event terms, and the registry entries do not specify the types of the 2 other adverse events. The record does not provide enough detail to assess event timing, severity beyond the serious-versus-other classification, relatedness, or outcomes. These safety figures therefore describe only the limited posted counts and enrollment, not a complete assessment of relative safety.

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

The result is principally a statement about the study’s incomplete enrollment, not an estimate of comparative efficacy. The trial was intended to evaluate EXPAREL delivered through TAP infiltration after spinal anesthesia in subjects undergoing elective cesarean section. It was terminated due to slow enrollment after 12 subjects were assigned to Standard of Care, and no subjects entered the EXPAREL/TAP group. The registry explicitly states that no conclusions can be drawn regarding the study endpoints.

The primary outcome was total postsurgical narcotic consumption in morphine equivalents through 72 hours postdose. The registry says the endpoint data refer to 7 participants who received rescue medication, but it does not give the mean or standard deviation in the registry record. More importantly, there are no outcome data from the EXPAREL/TAP arm. The record therefore does not show whether consumption differed between the planned groups, how large any difference might be, or how precisely a difference could be estimated.

This absence of a comparison is not evidence that the approaches have identical outcomes. It is also not evidence that one approach is superior or inferior. The record does not support either conclusion. Similarly, the absence of participants in the EXPAREL/TAP arm means its listed adverse-event counts cannot describe safety after exposure. The Standard of Care adverse-event counts are limited descriptive observations from the participants at risk in that group.

The trial’s non-randomized allocation and open-label design would also be relevant to any future interpretation of group differences. Even with enrollment in both arms, a non-randomized contrast could reflect differences between participants or care contexts, and open-label conduct may affect outcomes or reporting. These are general cautions about design, not claims that a particular bias occurred. In this trial, no comparative estimate is available to examine.

The practical statistical meaning is that the record documents a planned question and an enrollment outcome that did not permit that question to be answered. It does not provide a basis for a treatment recommendation, a quantitative effect estimate, or a comparative safety conclusion. The findings should be understood as incomplete evidence rather than as a positive, negative, or equivalent result.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a trial’s planned question and the evidence its actual enrollment can support. The registry describes a planned comparison of Standard of Care with EXPAREL/TAP, but reports that only the Standard of Care group enrolled participants. A study can have a clearly stated endpoint and intervention without generating an estimate that answers the intended comparative question.

Enrollment affects more than the precision of an estimate. When one planned group has no participants, a between-group effect is not merely imprecise; it is not estimable from the observed trial data. That distinction matters when interpreting a terminated study. The lack of an estimate should not be converted into a conclusion of no difference, and a reported count of zero in an empty group should not be mistaken for an observed outcome.

The record also highlights why design features remain relevant even when an endpoint is clearly defined. Non-randomized allocation and open-label conduct can complicate interpretation of comparisons. These features would call for careful consideration if both groups had enrolled; the absence of a second group prevents such an analysis. Statistical methods cannot compensate for the absence of data needed to form the contrast.

Finally, the record makes transparent several limits that are important to readers: the study was terminated due to slow enrollment, no analyses are listed, and the registry states that no endpoint conclusions can be drawn. Reporting those limits helps distinguish a study that has answered a question imprecisely from one that did not produce the comparison in the first place. For biostatisticians and clinical researchers, that distinction is central to responsible interpretation of incomplete trial evidence.

15. 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 most consequential limitation is that the study enrolled no participants into the EXPAREL/TAP group. The registry reports 12 subjects assigned to Standard of Care and explicitly says no subjects were enrolled into Group 2. This prevents estimation of the planned comparative effect on the primary endpoint and prevents a direct safety comparison.

The study was non-randomized and open-label. These design features would make causal interpretation more difficult even if both groups had enrolled. Because the record does not report a detailed allocation process or any adjustment strategy, the possible influence of participant or care differences cannot be assessed. The study’s multicenter designation does not provide information about site-level enrollment or variation in conduct.

Primary endpoint reporting is limited. The endpoint is defined as total postsurgical narcotic consumption in morphine equivalents through 72 hours postdose, and the outcome description refers to 7 participants who received rescue medication. The registry record does not report the endpoint mean, standard deviation, group-specific values, or how participants who did not receive rescue medication were handled. It also does not report individual data or a missing-data approach.

The registry records 0 analyses and does not report inferential results, confidence intervals, p-values, a statistical analysis plan, or a sample-size justification. It does not report an interim analysis plan. The adverse-event information is also limited: the types of the 2 other adverse events are not stated in the registry record, serious adverse-event terms are not listed, and deaths are not reported in the registry record. These limitations restrict conclusions to the study’s enrollment status and the descriptive counts that are recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Safety and Efficacy of EXPAREL When Administered Into the TAP in Subjects Undergoing Cesarean Section — NCT02353754.
• Registry record last updated 2021-03-26; status last verified 2021-03.
• Results first posted 2016-06-28.
• 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.

19. Record Summary

NCT02353754 was a Phase 4, multicenter, open-label, non-randomized parallel study of EXPAREL administered by TAP infiltration after bupivacaine spinal anesthesia for elective cesarean section. The planned comparison was with Standard of Care, described as intrathecal morphine injection with spinal anesthesia and no TAP block. The primary endpoint was total postsurgical narcotic consumption in morphine equivalents through 72 hours postdose.

The study is recorded as terminated due to slow enrollment. The registry reports 12 subjects assigned to Standard of Care and no subjects enrolled into EXPAREL/TAP. Endpoint data are described as referring to 7 participants who received rescue medication, but endpoint summary values and comparative analyses are not reported in the registry record. The record states that no conclusions can be drawn regarding the study endpoints.

For safety, the record lists 0 serious adverse events and 2 participants with other adverse events among 12 at risk in Standard of Care. The EXPAREL/TAP group had no participants at risk. The posted information does not support a comparative estimate of efficacy or safety.