A Health Economic Trial in Adult Patients Undergoing Ileostomy Reversal MA402S23B501: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Health Economic Trial in Adult Patients Undergoing Ileostomy Reversal MA402S23B501 (NCT01509638), a non-randomized phase 4 study. The primary outcome is Total Opioid Burden.

2. Clinical Question

3. Trial Design

This was a completed phase 4 health economic trial sponsored by Pacira Pharmaceuticals, Inc. The registry record lists the study start as 2012-03 and primary completion as 2012-10. Enrollment is recorded as 47. The study used a parallel-group model, non-randomized allocation, and no masking. The two intervention groups were standard of care and EXPAREL.

Standard care was IV morphine sulfate or a sponsor-approved equivalent delivered through a patient-controlled analgesia pump. The other group received bupivacaine liposome injectable suspension. Because assignment was non-randomized, the registry's caution is important: the arms are not a like-for-like control comparison. Differences in patient characteristics, care, or other factors could be associated with both group assignment and opioid use. The record does not report how treatment assignment was determined or whether analyses adjusted for group differences.

The primary outcome was a continuous measure summarized as a mean with standard deviation. The Safety Analysis Set included patients who underwent planned surgery; the record lists 22 in Group 1 and 25 in Group 2. The Efficacy Analysis Set was narrower: patients had planned surgery, met the stated criteria, gave informed consent, and, for Group 2, received EXPAREL. This set included 20 in Group 1 and 23 in Group 2. These are distinct analysis-population descriptions, not evidence that results were reported for either population.

The registry record identifies 10 outcome measures and lists secondary outcomes covering opioid-related adverse events, satisfaction, post-discharge experiences, and time to first opioid administration. It lists no analysis entries. The primary endpoint results, statistical plan, allocation process, and handling of missing outcome data 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.

Before assignment: 23 patients in Group 1 and 25 patients in Group 2 were enrolled. 22 patients from Group 1 and 23 patients from Group 2 were in the Safety Analysis Set (patients who underwent planned surgery). Efficacy Analysis Set was 20 patients from Group 1 and 23 from Group 2 (planned surgery, no exclusion criteria, informed consent, Group 2 received EXPAREL)

Overall Study

Analysis population for the primary outcome, as defined in the registry: 22 patients from Group 1 and 25 patients from Group 2 were in the Safety Analysis Set (patients who underwent planned surgery). Efficacy Analysis Set was 20 patients from Group 1 and 23 from Group 2 (planned surgery, no exclusion criteria, informed consent, Group 2 received EXPAREL)

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: 23 patients in Group 1 and 25 patients in Group 2 were enrolled. 22 patients from Group 1 and 23 patients from Group 2 were in the Safety Analysis Set (patients who underwent planned surgery).

6. Primary Endpoint

The registry lists the primary outcome as Total Opioid Burden, measured over Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.

Total opioid burden was the primary endpoint. It measured the total amount of opioid consumed after surgery, including IV and oral opioids, expressed in mg morphine equivalent. The observation period began at wound closure and ended when the hospital discharge order was written or at Day 30, whichever came sooner.

Using a morphine-equivalent measure allows opioid amounts across routes or opioid preparations to be expressed on a common scale, as described by the endpoint unit. The endpoint focuses on accumulated consumption over a defined postoperative period rather than on a single dose or a single time point. As a continuous outcome, it was summarized in the registry as a mean and standard deviation. The mean describes the group average, while the standard deviation describes how much individual values vary around that average.

This measure was relevant to the stated study aim of comparing opioid consumption between standard care and EXPAREL. The registry's brief summary also connects opioid use to possible hospitalization costs, but the listed primary endpoint is opioid burden, not cost. No group means, standard deviations, or contrast for opioid burden are reported in the registry record. Therefore, the endpoint's definition is available, but its observed comparative result and precision cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary endpoint as a continuous measure summarized by a mean and standard deviation. The following points explain these methods generally and how the available record bears on interpretation.

What does a mean summarize?

In general, a mean is an average across the observed values in a group. It gives a compact description of the level of a continuous outcome, such as total opioid burden. The standard deviation describes the spread of individual values around the mean. A larger standard deviation indicates more variability among observations, while a smaller one indicates that observations are more closely clustered around the mean. The mean alone does not show the full distribution, and the standard deviation is not a measure of uncertainty in the estimated mean.

For this trial, the primary endpoint is expressed in mg morphine equivalent and includes IV and oral opioid consumption over a specified postoperative period. The registry says the measure was to be reported as a mean and standard deviation, but does not provide either statistic for either group. It is therefore not possible to describe the observed average, the variability, or the magnitude of a group contrast from the registry record.

How is uncertainty usually described?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of the statistical method. It helps readers judge the precision of an estimate: a narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. A confidence interval around a group contrast would help assess which effect sizes remain plausible, not just whether a test crosses a chosen threshold.

No confidence interval or other uncertainty interval for the primary outcome is reported in the registry record. A p-value is also not reported. Without an estimate and its uncertainty, the posted record does not support a statistical assessment of the primary comparison. The absence of these entries is not evidence that the groups were equal; it means the comparative result is unavailable in the record.

Why does allocation matter?

In general, random allocation can reduce systematic differences between treatment groups, because assignment is determined by chance rather than by patient or clinician characteristics. Non-randomized allocation does not provide that protection. If factors related to prognosis influence which group a patient enters, a raw difference in outcomes can reflect both the intervention and those underlying differences. Statistical adjustment can sometimes address measured differences, but it cannot necessarily remove bias from unmeasured factors.

This study is explicitly listed as non-randomized, and the registry cautions that its arms are not a like-for-like control comparison. The allocation process and any adjustment strategy are not reported in the registry record. Consequently, even if comparative outcome estimates were available, the design would require careful assessment of possible confounding before attributing a group difference to the treatment.

What do the analysis populations mean?

The Safety Analysis Set is described as patients who underwent planned surgery. The Efficacy Analysis Set applies additional conditions, including planned surgery, no exclusion criteria, informed consent, and receipt of EXPAREL for Group 2. Such population definitions can affect which observations contribute to safety and efficacy summaries. In general, analyses based on different populations can answer different questions and may yield different estimates, particularly if inclusion depends on events after assignment.

The record lists the sizes of both sets but does not provide primary outcome results by set, nor does it explain how participants excluded from the efficacy set were handled in analyses. The populations should therefore be treated as descriptions of who was included, not as evidence that a particular analysis method was used.

What can planning calculations show?

In general, sample-size planning explores how many participants per arm might be needed to detect a prespecified effect under stated assumptions. The registry's planning description uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; it says the target effect is a stated fraction of the observed effect. These are planning assumptions, not outcomes from the trial. The record does not report a sample-size justification from the trial's own design. Any planning illustration based on the observed effect is not observed power and does not replace the missing estimate and uncertainty for the actual comparison.

For time-to-event outcomes, a different framework may express planning in terms of total events; for other outcomes, the planning description refers to participants per arm. These general distinctions do not establish that a particular planning calculation was prespecified or used in this study. A statistical analysis plan, including the planned tests, covariate adjustment, and approach to multiple outcomes, is not reported in the registry record.

How should the available safety summaries be read?

The record gives counts of patients with serious and other adverse events in each group. These are descriptive summaries. In general, adverse-event comparisons require attention to how events were defined, how long patients were followed, whether multiple events per patient are represented, and how group differences may reflect non-randomized assignment. The record does not provide enough detail to resolve those questions for the listed summaries. The serious-event terms are reported with percentages, but no comparative estimate or uncertainty interval is given.

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("Group 1 Standard of Care", "Group 2 EXPAREL")
n   <- c(20, 23)
m   <- c(67.7, 38.41)
sp  <- c(46.64, 45.85)
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  Group 1 Standard of Care  20  67.700  46.640  45.872  89.528
CARM  Group 2 EXPAREL  23  38.410  45.850  18.583  58.237

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary opioid-burden endpoint and secondary measures related to opioid adverse events, patient satisfaction, post-discharge experience, and time to first opioid administration. When a study evaluates multiple outcomes, there is a general statistical issue of multiplicity: the more hypotheses examined, the greater the chance that at least one result may appear noteworthy by chance if each is judged separately. A prespecified hierarchy or adjustment can help address that issue. The registry record does not report a multiplicity strategy, outcome hierarchy beyond the primary designation, or a statistical analysis plan.

The record lists no analysis entries. It does not provide primary outcome estimates, secondary outcome results, p-values, or confidence intervals. Results for the listed secondary outcomes are not reported in the registry record. This means that readers cannot determine which outcomes were analyzed, whether all planned outcomes were reported, or how any multiplicity concerns were handled.

Missing-data methods are also not reported in the registry record. The record describes a Safety Analysis Set and an Efficacy Analysis Set, with different inclusion conditions, but does not state whether outcome observations were missing, how missing values were handled, or whether sensitivity analyses were performed. The population definitions alone do not explain the reasons for exclusions or their potential effect on estimates.

Interim analyses and stopping rules are not reported in the registry record. The record also does not state whether an analysis plan was finalized before outcome data were examined. These omissions limit assessment of how outcomes were selected, how incomplete observations were treated, and how the reported populations relate to the intended study population.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal hemorrhage (4.0%), anastomotic leak (4.0%), peritonitis (4.0%), small intestinal obstruction (4.0%), pneumonia aspiration (4.0%).

The registry reports serious adverse events for each group. In Group 1, 0 of 22 patients were recorded as affected; in Group 2, 3 of 25 patients were recorded as affected. It separately reports other adverse events affecting 18 of 22 patients in Group 1 and 15 of 25 patients in Group 2. These counts should be read as descriptive summaries for the groups, not as estimates of causal treatment effects.

The record lists the following serious adverse-event terms at 4.0% each: gastrointestinal hemorrhage, anastomotic leak, peritonitis, small intestinal obstruction, pneumonia aspiration, and systemic inflammatory response syndrome. The registry does not provide further detail on event timing, seriousness criteria, attribution, or the number of events represented by each term. Death counts are not reported in the registry record.

Because allocation was non-randomized, differences in adverse-event counts may reflect differences between the groups as well as treatment exposure. The posted counts do not show whether an event was caused by an intervention, and they do not provide uncertainty estimates for between-group comparisons. They should not be interpreted as proof of harm or safety.

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

The record establishes what the trial intended to compare: opioid consumption after surgery under standard care versus EXPAREL. It also specifies the opioid-burden endpoint, its measurement period, the analysis populations, and selected adverse-event counts. These details help define the question and describe some of the recorded study information.

The central efficacy result is not reported in the registry record. Group means and standard deviations for total opioid burden are absent, as are an estimated difference, a confidence interval, and a p-value. The record therefore does not show whether the observed opioid consumption was higher or lower in either group, by how much, or with what precision. It does not establish that EXPAREL reduced opioid consumption, nor does it establish that opioid consumption was unchanged.

The non-randomized design further limits causal interpretation. Without random assignment, group differences could be related to factors other than the intervention. The registry does not describe the allocation mechanism or statistical adjustment for possible differences. The counts of serious and other adverse events are likewise descriptive and should not be treated as causal comparisons.

The study's health-economic framing and brief summary mention possible hospitalization costs, but the listed primary endpoint measures opioid consumption. Cost results are not reported in the registry record. Nor are results for the listed secondary outcomes reported in the record presented. The available information therefore supports an account of the study question and design, but not a conclusion about comparative effectiveness, cost consequences, or the precision of any treatment contrast.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported treatment contrast are both needed for statistical interpretation. The registry specifies total opioid burden in mg morphine equivalent and defines its postoperative observation window. It also states that the endpoint was summarized as a mean and standard deviation. Those details make the intended measurement understandable, but without the group summaries and an estimate of their contrast, readers cannot assess the result.

The design also highlights the distinction between association and causal effect. A parallel-group comparison can be clinically relevant while still being vulnerable to baseline differences when treatment allocation is non-randomized. The registry explicitly cautions that the arms are not a like-for-like control comparison. Knowing that limitation matters when interpreting any group comparison, including safety counts.

The registry lists multiple secondary outcomes and selected adverse-event information, but no analysis entries or primary outcome results. This makes completeness and multiplicity difficult to assess. A clear analysis plan, explicit population handling, and outcome estimates with uncertainty would help readers understand which comparisons were planned and how much confidence to place in them.

Finally, the study is described as health economic, while the primary endpoint reported is opioid consumption. These are related but distinct questions. Evidence about opioid use alone would not quantify hospital costs; cost outcomes and their analysis would be needed for that. The record therefore provides a useful case for distinguishing a study's motivation from the outcome actually reported.

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 primary limitation for interpreting the efficacy question is that the registry record does not report results for total opioid burden. Means, standard deviations, a between-group estimate, and measures of uncertainty are not reported. Without those results, the principal comparison cannot be evaluated statistically.

Allocation was non-randomized, and the registry warns that the arms are not a like-for-like control comparison. The method used to assign patients to groups, baseline characteristics, and any adjustment for confounding are not reported in the registry record. This leaves the extent of group comparability unclear.

The record defines both a Safety Analysis Set and an Efficacy Analysis Set, but does not report primary outcome results for either population or explain the treatment of participants not included in the efficacy set. Missing-data methods, reasons for exclusions, and sensitivity analyses are not reported in the registry record. The analysis plan, including multiplicity procedures and interim analyses, is also not reported.

The posted safety information consists of group counts and selected serious-event terms. Detailed event definitions, event-level timing, attribution, and uncertainty for comparisons are not reported in the registry record. Death counts are not reported. The listed secondary outcomes do not have results in the record presented, and the health-economic framing is not accompanied by reported cost results. These limitations restrict conclusions to the study design and descriptive information that the record actually contains.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Health Economic Trial in Adult Patients Undergoing Ileostomy Reversal MA402S23B501 — NCT01509638.
• Registry record last updated 2014-03-06; status last verified 2014-01.
• Results first posted 2014-03-06.
• 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.

19. Record Summary

The registry record describes a completed, non-randomized phase 4 parallel-group trial of standard care versus EXPAREL in adults undergoing ileostomy reversal. The study lists enrollment of 47, no masking, and primary completion in 2012-10. Standard care consisted of IV morphine sulfate or a sponsor-approved equivalent through a patient-controlled analgesia pump; the EXPAREL group received bupivacaine liposome injectable suspension.

The primary endpoint was total IV and oral opioid consumption in mg morphine equivalent from wound closure until the hospital discharge order was written or Day 30, whichever came sooner. The record describes Safety and Efficacy Analysis Sets and reports selected adverse-event counts. It does not report primary outcome results, statistical estimates, uncertainty intervals, cost results, or results for the listed secondary outcomes. Because allocation was non-randomized, the registry cautions against treating the arms as a like-for-like control comparison.