Four Quadrants Transverse Abdominus Plane (4Q-TAP) Block With Plain and Liposomal Bupivacaine vs. Thoracic Epidermal Analgesia (TEA) in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) on an Enhanced Recovery Pathway: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Four Quadrants Transverse Abdominus Plane (4Q-TAP) Block With Plain and Liposomal Bupivacaine vs. Thoracic Epidermal Analgesia (TEA) in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) on an Enhanced Recovery Pathway (NCT03359811), a randomized phase 3 study. The primary outcome is Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2.

2. Clinical Question

3. Trial Design

The registry describes a phase 3, randomized, parallel-group trial comparing 4Q-TAP blocks with standard-of-care TEA in patients having CRS-HIPEC. Masking is listed as none. The registry lists enrollment as 75, while the brief summary says that up to 140 participants would be enrolled. The record does not explain the difference between those figures; they should not be treated as interchangeable measures of enrollment.

The intervention descriptions distinguish the methods of analgesia. The 4Q-TAP arm received an ultrasound-guided block before incision, using a solution described as containing bupivacaine HCl and liposomal bupivacaine. The TEA arm received an epidural catheter before induction, with local anesthetic and possible opioid use determined by the anesthesia provider’s clinical judgment. The registry calls TEA standard of care and describes the comparison as investigational.

The primary endpoint was QoR-15 change from preoperative assessment to postoperative day 2, measured 48 hours after surgery. The posted arm-level results are medians with full ranges. The registry reports 33 participants in the TEA arm and 35 in the 4Q-TAP arm for this outcome. It does not report a comparative effect estimate, confidence interval, or test result.

Secondary outcomes include postoperative pain, total opioid consumption, length of stay, adverse events, opioid-related adverse events, and postoperative complications and morbidity. The registry identifies six posted secondary outcomes, but the record does not provide comparative analyses for them. The study status is completed. The record does not report further details about sequence generation, allocation concealment, protocol deviations, or the timing of the final analysis.

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: A total of 75 participants consented, 5 participants were inevaluable.

Overall Study

Reasons for not completing this period:

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: Baseline demographics data is only available for the participants who completed the study

6. Primary Endpoint

The registry lists the primary outcome as Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2, measured over 48 hours after CRS-HIPEC surgery.

The primary endpoint is the change in QoR-15 from before surgery to postoperative day 2, with assessment described as occurring 48 hours after CRS-HIPEC. QoR-15 is a validated questionnaire-based scoring system intended to quantify early postoperative health status. Its possible score runs from 0 to 150, and higher scores indicate a better outcome. A change score focuses on how the reported score differs across the two assessment times, rather than describing only the postoperative score.

The registry reports the endpoint as a median with a full range for each arm. A median describes the middle of the ordered observations and can be useful when a distribution is skewed or contains unusually high or low values. The full range gives the lowest and highest reported values, but it does not describe how observations are distributed between those extremes. It also does not show how precisely the median or the between-group contrast has been estimated.

The arm medians are -45.0 for TEA and -50.0 for 4Q-TAP. Their full ranges are -89.0 to 0.0 and -88.0 to 23.0, respectively. These are arm-level summaries, not an adjusted or unadjusted estimate of the treatment contrast. The registry’s description says the endpoint is change from pre-op to POD2 but does not specify the subtraction convention. The values therefore should be read as reported change scores, without assigning a direction to the change beyond the information stated in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended to make the treatment groups comparable, on average, with respect to factors that could affect outcomes. It does not guarantee that the groups will be identical on every characteristic, especially in a trial of limited size. The registry identifies the allocation as randomized and the model as parallel, meaning participants were assigned to one of the two analgesia groups rather than crossing between them. It does not describe the randomization sequence, allocation concealment, or whether stratification was used.

What does a median describe?

As a general statistical explanation, the median is the central value after observations are ordered. Unlike a mean, it is less affected by a small number of unusually high or low observations. That can make it a useful summary when outcomes are not symmetrically distributed. A median is still only one feature of the data: it does not describe the full distribution or the precision of a difference between groups.

The registry reports the primary outcome using medians and full ranges. A full range records the lowest and highest observed values. It is sensitive to extreme observations and gives no direct information about the density of observations within the range. Overlap between two ranges does not by itself determine whether groups differ, and non-overlap is not a substitute for an inferential analysis. The record does not report an interquartile range, standard deviation, standard error, or confidence interval for the primary outcome.

What would a comparative estimate add?

As a general statistical explanation, a treatment comparison should summarize the contrast between groups and quantify uncertainty around that contrast. A confidence interval gives a range of values compatible with the data and the method’s assumptions; it helps readers assess both the possible size and the precision of an effect estimate. A p-value addresses compatibility with a specified null hypothesis under a statistical model, but it does not measure clinical importance or the probability that a hypothesis is true. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.

The primary outcome is a change score. In general, analyzing change can account for the starting measurement in a different way from analyzing the postoperative score alone. The interpretation depends on how change is defined and on the analysis method. The registry says the measure is QoR-15 change from Pre-Op to POD2 but does not state the subtraction convention or describe an adjusted model. It is therefore not possible to infer those analytic choices from the reported medians.

How does non-inferiority differ from superiority?

As a general statistical explanation, a non-inferiority study asks whether the result is sufficiently close to the comparator, according to a prespecified margin. The margin sets the largest difference that would still be considered compatible with non-inferiority. The estimate and its uncertainty must be interpreted relative to that margin. A result that does not show a statistically detectable difference is not, by itself, evidence of non-inferiority. Although the trial title calls this a non-inferiority trial, the margin, hypothesis, test, confidence-interval approach, and analysis population are not reported in the registry record.

General planning illustrations based on an observed effect are not the same as the trial’s original sample-size justification. Such illustrations depend on assumptions, including the target effect and statistical method. The registry record describes planning illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect set as a stated fraction of the observed effect. The resulting planning values are not reported in the record. They should not be interpreted as observed power or as evidence about the trial’s actual design rationale.

What can be concluded from the posted summaries?

The posted primary results support a description of the arm-level medians and ranges, but not a formal inference about a between-group effect. The record lists no posted analyses. It does not report a model, a test statistic, a confidence interval, or adjustment for covariates. No particular analytic method should be presumed from the endpoint’s use of medians: the method used to compare groups is not reported.

As a general matter, unusually variable outcomes can make estimates less precise. Over-dispersion means that variability is greater than a chosen model would expect; if present, it can make model-based standard errors too small unless the model accounts for it. The registry record does not report a dispersion assessment or a model for the QoR-15 outcome, so there is no basis to say whether over-dispersion was assessed or relevant in this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes in addition to the primary QoR-15 endpoint. These cover postoperative pain, total opioid consumption, length of stay, adverse events, opioid-related adverse events, and postoperative complications and morbidity. The registry record does not report a plan for controlling the chance of false-positive findings across multiple outcomes, such as a testing hierarchy or a multiplicity adjustment. It also does not provide comparative results for the listed secondary outcomes. In the absence of an analysis plan and results, no conclusion about multiplicity-adjusted evidence can be drawn.

Missing outcome data can affect both the number of observations analyzed and the interpretation of results. The registry does not report the number of missing baseline or POD2 QoR-15 scores, reasons for missingness, or methods used to handle missing data. It also does not state whether participants were analyzed according to randomized assignment or according to treatment received. The outcome counts in the two arms are reported, but the analysis population they represent is not defined in the registry record.

The record does not report a prespecified statistical analysis plan, interim analyses, subgroup analyses, or a sample-size justification. The trial title indicates a non-inferiority objective, but the registry does not state the margin or the analysis population used for that objective. These omissions prevent assessment of whether the reported outcome summaries align with a prespecified testing strategy or whether alternative analyses were performed.

These details are not evidence that particular procedures were absent from the trial. They are details that are not reported in the registry record, so they cannot be used to evaluate the handling of multiplicity, missing data, or analysis populations.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intraabdominal abscess (2.9%).

The registry reports serious adverse events for 0 of 33 participants in the TEA group and 1 of 35 participants in the 4Q-TAP group. It reports other adverse events for 17 of 33 and 16 of 35, respectively, and deaths for 0 participants in each group. These are counts within the registry’s reported groups. The record does not provide a statistical comparison, confidence intervals, or an explanation of how events were attributed to treatment.

The registry lists Intraabdominal Abscess at 2.9% among the top serious adverse-event terms. It does not identify the treatment group for that term in the information reported, so the term should not be assigned to either arm based on these data alone. Nor does a listed event term explain its severity, timing, duration, or relationship to the procedure or intervention.

Adverse-event counts are descriptive and should be read alongside the number at risk reported for each group. A small count does not by itself establish that an event is unrelated to treatment, and a difference in counts does not by itself establish a treatment effect. The registry record does not report event-level detail or a formal safety analysis. These figures therefore describe what was posted, not a comparative estimate of safety.

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

The results establish that the registry reports QoR-15 change summaries for both treatment groups at the stated 48-hour assessment. The reported medians are -45.0 for TEA and -50.0 for 4Q-TAP, with full ranges of -89.0 to 0.0 and -88.0 to 23.0. The record also reports adverse-event counts by group. These statements describe the posted results without interpreting them as a treatment effect.

The results do not establish that the approaches are equivalent, that 4Q-TAP is non-inferior to TEA, or that one approach has better quality of recovery. A non-inferiority conclusion requires the margin and an appropriate comparative analysis; these are not reported in the registry record. Nor can the arm medians alone show how precise a treatment contrast is. No comparative estimate or confidence interval is posted for the primary endpoint.

The QoR-15 score ranges from 0 to 150, and higher scores indicate better outcome, but the record does not state the subtraction convention for the change score. Without that detail, the negative values should not be translated into a specific direction of change. The record also does not describe missing-score handling or define the analysis population represented by the outcome counts.

The safety counts similarly do not establish comparative risk. The record gives serious and other adverse-event counts, but does not provide a formal comparison, event-level timing, or treatment attribution. The posted figures cannot by themselves determine whether an event was caused by the block, epidural, surgery, or another factor.

For readers, the most defensible interpretation is narrow: the registry provides arm-level descriptive results for the primary outcome and event counts, while leaving important inferential and analytic details unreported. The figures can inform an account of what was recorded, but they do not support a claim of benefit, harm, equivalence, or non-inferiority on their own.

13. Why This Trial Matters Statistically

This trial addresses a clinically important statistical comparison because the two groups receive different forms of analgesia during recovery from CRS-HIPEC. The question is framed around quality of recovery rather than a single isolated symptom, using QoR-15, a validated measure of early postoperative health status. The registry also identifies pain, opioid consumption, length of stay, adverse events, and complications as secondary outcomes, reflecting several dimensions that may matter when comparing recovery strategies.

The design is described as randomized and parallel, which is relevant to how a treatment contrast can be interpreted. Random allocation is intended to reduce systematic differences between groups, although the registry does not provide details of sequence generation or concealment. The trial title states a non-inferiority objective, making the margin and analysis strategy especially important for interpreting the primary result. Those details are not reported in the registry record.

The posted primary endpoint summaries illustrate why descriptive statistics and inferential results are not interchangeable. Medians and ranges show the reported arm distributions in a compact form, but they do not quantify the uncertainty around the between-group contrast. Without a comparative estimate and its uncertainty, readers cannot determine whether the data meet the stated non-inferiority objective.

The registry also highlights an important reporting distinction: it lists both planned enrollment in the brief summary and enrollment in the record, with different figures, but does not explain the difference. Clear reporting of participant flow, analysis populations, missing data, and analysis methods would help readers assess what each result represents. These considerations matter when using a trial record to understand the strength and limits of its statistical evidence.

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 primary outcome is reported as arm-level medians and full ranges, without a comparative estimate or measure of uncertainty. The registry record does not report a confidence interval, p-value, or statistical test for the QoR-15 comparison. The full range also does not show the distribution of values within each arm. As a result, the posted primary results do not support a formal inference about the treatment contrast.

The title describes a non-inferiority randomized controlled trial, but the non-inferiority margin, analysis method, and analysis population are not reported. The registry also does not state the direction used to calculate change from pre-op to POD2. These omissions limit interpretation of both the purpose and the numerical direction of the reported change scores.

The record lists outcome counts of 33 for TEA and 35 for 4Q-TAP, but does not explain how those counts relate to enrollment, randomization, or missing assessments. The brief summary says up to 140 participants would be enrolled, while the registry lists enrollment as 75; the record does not reconcile those statements. Participant flow, missing-data methods, and reasons for non-observation are not reported.

The registry does not report details of randomization, allocation concealment, protocol deviations, multiplicity handling, interim analyses, or the statistical analysis plan. Secondary outcomes are listed, but comparative results are not reported. Safety information is presented as counts, with limited event-level detail; the treatment group for the listed serious-event term is not specified in the reported information. These are limitations of what the registry record documents, not proof that the trial did not collect or analyze additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Four Quadrants Transverse Abdominus Plane (4Q-TAP) Block With Plain and Liposomal Bupivacaine vs. Thoracic Epidermal Analgesia (TEA) in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) on an Enhanced Recovery Pathway — NCT03359811.
• Registry record last updated 2022-02-18; status last verified 2022-01.
• Results first posted 2022-02-18.
• 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

The registry describes a completed phase 3 randomized, parallel-group trial comparing 4Q-TAP blocks with standard-of-care TEA for patients undergoing CRS-HIPEC. Masking is listed as none. The primary endpoint is QoR-15 change from pre-op to postoperative day 2, assessed 48 hours after surgery. QoR-15 ranges from 0 to 150, with higher scores indicating a better outcome.

Median changes are reported as -45.0 for TEA and -50.0 for 4Q-TAP, with full ranges of -89.0 to 0.0 and -88.0 to 23.0. The registry also reports serious adverse events, other adverse events, and deaths by group. It does not report comparative analyses, confidence intervals, p-values, a non-inferiority margin, or missing-data methods. The brief summary’s stated enrollment of up to 140 and the registry enrollment of 75 are not reconciled in the record.