Programmed Intermittent Bolus Dosing Versus Continuous Epidural Infusion for Epidural Analgesia in Abdominal Surgery.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Programmed Intermittent Bolus Dosing Versus Continuous Epidural Infusion for Epidural Analgesia in Abdominal Surgery. (NCT03307174), a randomized phase 4 study. The primary outcome is Total Local Anesthetic Utilized in First 24 Hours.

2. Clinical Question

The registry record asks whether the method used to administer epidural medication is associated with differences in local anesthetic consumption during the first 24 hours after abdominal surgery. It compares continuous epidural infusion with programmed intermittent epidural boluses. Total local anesthetic consumption is the primary endpoint, and total opioid consumption, pain measures, functional measures, satisfaction, and hypotension are among the other outcomes described in the study summary.

This is a comparison of administration strategies within a surgical population, not a comparison of epidural medication with no epidural. The record describes the consumption outcome as a surrogate marker for the quality of epidural anesthesia. The statistical results therefore address the recorded endpoint and its distribution; they do not, on their own, establish a difference in pain, function, satisfaction, or other patient experience.

3. Trial Design

The registry describes a prospective, randomized, single-masked, parallel-group phase 4 study sponsored by the University of California, San Francisco. It is marked completed. The recorded study start is 2016-04-14, the primary completion date is 2019-02-28, and enrollment is 120. The record does not identify who was masked.

The two groups differed in how the epidural medication was administered. The continuous epidural infusion group received a constant infusion of 0.062% bupivacaine with 2mcg/ml fentanyl at 8ml/hr. The programmed intermittent epidural bolus group received the same stated combination as a 4ml bolus every 30 minutes. Both descriptions mention patient-controlled epidural analgesia, but the full patient-controlled settings are not reported in the registry record.

The study summary identifies abdominal surgery, including colorectal, gynecologic, surgical oncology, and urological procedures where epidural anesthesia could be used. The registry does not report the number of participants in each surgical category or further details of eligibility. The rationale described in the record is to evaluate the administration approaches in a surgical population, where their effects were described as not yet elucidated.

The posted primary analysis includes 44 participants in the continuous infusion group and 52 in the intermittent bolus group. The outcome description says that 2 patients in the continuous infusion group and 1 patient in the intermittent bolus group were not included in that analysis because of missing data. The relationship between those analysis counts and total enrollment, beyond this stated missing-data note, is not reported in the registry record. The analysis population definition and any further exclusions are also 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: Patients were not randomized to study groups if epidurals were not able to be successfully placed. 2 subjects in the CEI group were no included in the analysis due to missing data 1 subject in the PIEB group was not included in the analysis due to missing data

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Note that 2 patients in the CEI group and 1 patient in the PIEB group was not included in the analysis due to missing data.

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 Total Local Anesthetic Utilized in First 24 Hours, measured over In first 24 hours.

The primary endpoint is total local anesthetic utilized in the first 24 hours. The registry defines it as the total amount consumed while the epidural was in place, recorded on the infusion pump, and gives milligrams as the unit. The posted summary describes the endpoint using a median and an interquartile range for each group.

Consumption is used in the study summary as a surrogate marker for the quality of epidural anesthesia. In general, a recorded amount of medication is an observable measure of use, whereas quality of analgesia is a broader clinical concept. The registry also identifies pain scores, functional measurements, patient satisfaction, and hypotension as secondary outcomes, providing distinct kinds of information about the experience and consequences of the administration approaches.

The endpoint should therefore be interpreted narrowly: it measures local anesthetic use during the stated period, not pain relief itself. The record does not describe a minimum clinically important difference, a target level of consumption, or a threshold by which one amount would represent adequate analgesia. Those details are not reported in the registry record.

For the primary outcome, the continuous infusion group had a median of 126 mg, with an interquartile range from 120 to 134 mg. The intermittent bolus group had a median of 123 mg, with an interquartile range from 115 to 136 mg. These summaries describe the observed distributions; the interquartile ranges are not confidence intervals for the difference between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is summarized with a median and interquartile range, and the registry reports a Wilcoxon (Mann-Whitney) test for the two groups. The test is a rank-based method: in general, it compares the relative ordering of observations across groups rather than comparing means directly. Its interpretation is not automatically a test of medians alone. A median-focused interpretation requires assumptions about the shapes of the group distributions; those distributional details are not reported in the registry record.

What do the medians and interquartile ranges describe?

In general, the median is the central observation in an ordered distribution. The interquartile range spans the middle half of observations and describes variability among participants. Here, the reported median and interquartile range summarize local anesthetic consumption in each arm. They are descriptive statistics, not estimates of the uncertainty around the between-group effect. The interquartile ranges should not be read as confidence intervals.

The registry reports a p-value of 0.74 for the primary Wilcoxon comparison. In general, a p-value describes how compatible the observed data are with a specified null model, assuming that model and the test assumptions hold. It does not measure the size or clinical importance of an effect, and it is not the probability that the null hypothesis is true. The record does not provide a primary effect estimate with a confidence interval, so the uncertainty around a directly stated between-group contrast is not available from the posted primary analysis.

What does the secondary risk difference represent?

The hypotension comparison is expressed as a risk difference for programmed intermittent epidural bolus relative to continuous epidural infusion. The posted estimate is 0.142, and the confidence interval is -0.034 to 0.318. In general, a risk difference subtracts the event proportion in one group from the event proportion in the other, using the stated comparison direction. A value of zero corresponds to no difference in the proportions. The interval includes zero, so the posted estimate is compatible with values on either side of zero under the interval procedure used. The confidence level and the specific method used to form this interval are not reported in the registry record.

The unadjusted p-value for this secondary comparison is 0.124. The posted comparison also gives the group proportions as 0.204 for continuous infusion and 0.346 for intermittent bolus. The risk difference is an absolute measure; it should not be confused with a relative measure such as a risk ratio or odds ratio. Those relative measures are also listed in the comparison output, but the interpretation focuses on the risk difference and its interval. Because the analysis is unadjusted, it does not account for testing multiple secondary outcomes.

How should the planning illustration be read?

The registry's sample-size illustration is calculated from the observed hypotension effect, not from the trial's original design and not from the primary local anesthetic endpoint. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is represented as a fraction of the observed effect.

For planning at 100% of the observed effect, the illustration gives 156 participants per arm for 80% power and 208 participants per arm for 90% power. At 75% of the observed effect, it gives 265 participants per arm for 80% power and 355 participants per arm for 90% power. At 50% of the observed effect, it gives 570 participants per arm for 80% power and 763 participants per arm for 90% power. These are planning illustrations under the stated assumptions, not observed power and not a report of the original enrollment justification.

In general, power is a property of a design under assumed effect size, variability, significance threshold, and analysis method. A post hoc calculation based on an observed effect does not establish what the trial's power was before the data were collected. The original sample-size justification and the protocol's target effect are not reported in the registry record. The illustration is specific to hypotension, so it does not quantify power for the primary consumption outcome.

Why do missing data and multiple outcomes matter?

The primary outcome description identifies 2 continuous infusion participants and 1 intermittent bolus participant who were not included because of missing data. In general, excluding participants with missing outcomes can affect results when the reasons for missingness are related to group assignment or outcome values. The registry does not report a missing-data method beyond the exclusion note, nor does it describe sensitivity analyses. The consequences cannot be assessed from the available information alone.

The record describes multiple secondary outcomes in addition to the primary endpoint. In general, testing many outcomes can increase the chance of at least one apparently unusual result if each is assessed without adjustment. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for interpreting secondary tests. Accordingly, unadjusted secondary findings warrant more caution than a single primary comparison defined in advance.

10. Analyses Reported by the Sponsor

The posted primary analysis reports a Wilcoxon (Mann-Whitney) test with p = 0.74, alongside the group medians and interquartile ranges. No recalculated primary contrast or primary p-value is reported, so there is no independent numerical re-calculation of that primary test to compare with the registry's result. The primary values should therefore be read as the registry's reported analysis rather than as a separately reproduced calculation.

For hypotension, an unadjusted risk-difference calculation is posted, with an estimate of 0.142, a confidence interval from -0.034 to 0.318, and an unadjusted p-value of 0.124. The registry does not list a reported analysis for this secondary outcome. The available record indicates no discrepancy for the calculation, but the result remains an unadjusted secondary comparison and should not be treated as the primary trial conclusion.

In general, a simple re-calculation from group summaries can be useful as a check of an unadjusted comparison, but it does not replace a trial's prespecified analysis. A difference between a sponsor's analysis and a simple re-calculation, if present, would make the sponsor's own analysis the primary reference. No such discrepancy is indicated for the posted calculation. Details of the primary analysis beyond its test name and p-value are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description notes that 2 participants in the continuous epidural infusion group and 1 participant in the programmed intermittent epidural bolus group were not included in the primary analysis because of missing data. The record does not state the reasons for missingness, the method used to handle missing observations, or whether any imputation was performed. It also does not report sensitivity analyses assessing how alternative missing-data assumptions might affect the primary result.

The number randomized to each arm is not reported in the primary analysis summary. The posted primary analysis includes 44 participants in the continuous infusion group and 52 in the intermittent bolus group, while total enrollment is 120. The registry record does not explain the difference between total enrollment and those analysis counts, beyond the specific missing-data note. It does not identify an intention-to-treat, per-protocol, or other analysis population, and further exclusions are not reported in the registry record.

The study has a primary endpoint and multiple secondary outcomes. The record does not report whether the primary endpoint was formally prioritized in a testing hierarchy, whether secondary tests were adjusted for multiplicity, or how exploratory results were distinguished from confirmatory results. In general, when several outcomes are tested without adjustment, the chance of observing at least one nominally significant result can rise. Therefore, secondary results should be interpreted with caution unless their analysis plan and multiplicity handling are clear.

The registry lists one reported analysis for the primary outcome. It does not provide information about interim analyses, stopping rules, protocol deviations, or a statistical analysis plan. These elements should not be inferred from the randomized design or the reported p-value. Their status is not reported in the registry record.

12. 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 no serious adverse events affecting participants in either group: the serious-event count is 0 among 44 participants at risk in the continuous epidural infusion group and 0 among 52 participants at risk in the programmed intermittent epidural bolus group. Deaths are also reported as 0 in both groups. The record lists no specific serious adverse-event terms.

These figures describe what was recorded in the registry for the stated groups. They do not establish that serious events are impossible, and the small group counts limit how much can be inferred about uncommon events. The registry does not provide further detail on event definitions, monitoring procedures, or the period used for serious-event reporting, beyond the posted figures.

The registry separately reports other adverse events affecting 9 participants in the continuous infusion group and 18 in the intermittent bolus group. These are listed separately from serious adverse events and should not be combined with the serious-event counts. The record does not provide event descriptions or an adjusted comparison for these figures. They are descriptive safety counts, not evidence by themselves that one administration strategy caused a difference.

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

The primary result describes local anesthetic consumption in the first 24 hours among participants included in the analysis. The medians were 126 mg with continuous epidural infusion and 123 mg with programmed intermittent epidural boluses, and the reported Wilcoxon comparison had p = 0.74. This does not demonstrate a statistically clear difference in the primary comparison.

It also does not establish equivalence. A non-significant result is not proof that the underlying outcomes are the same, particularly when the registry does not report a confidence interval for the primary contrast or a prespecified equivalence margin. The primary result gives no direct measure of the range of plausible differences between strategies.

The endpoint is medication consumption, described as a surrogate for epidural anesthesia quality. It is not itself a direct measure of pain relief, functional recovery, satisfaction, or overall clinical benefit. The study summary lists several such secondary measures, but numerical results for most are not reported in the registry record. Thus, conclusions about those dimensions cannot be drawn from the primary endpoint alone.

The hypotension comparison is a separate secondary analysis, and its unadjusted estimate and interval should be interpreted in that context. It should not be used as a replacement for the primary endpoint or as a definitive safety conclusion. Likewise, the serious adverse-event counts are descriptive and do not establish the absence of risk.

In general, a trial result is most informative when the endpoint, effect estimate, uncertainty, analysis population, and missing-data handling can all be considered together. Here, the posted summaries support a narrow reading of the primary test, while important details about the analysis plan, primary contrast uncertainty, and missing data are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why the choice of summary and test matters in clinical research. Local anesthetic consumption is summarized with medians and interquartile ranges, and the primary comparison uses a rank-based Wilcoxon (Mann-Whitney) test. Those choices are suited to describing and comparing distributions without relying on a comparison of means, but the output still needs an effect estimate and uncertainty interval to show the size and precision of the contrast clearly.

The result also demonstrates the distinction between failing to detect a difference and demonstrating equivalence. The reported p-value does not establish that the approaches are identical, while the registry does not provide an equivalence margin or a primary contrast interval. Readers therefore need to avoid turning a non-significant result into a claim of sameness.

A second statistical issue is the relationship between surrogate outcomes and outcomes that directly describe participants' experience. Consumption is a measurable endpoint that the study summary uses as a surrogate for epidural anesthesia quality. Pain, function, satisfaction, and hypotension are separate dimensions. Without their numerical results, the endpoint set cannot be synthesized into a broad statement about the comparative clinical experience.

Finally, the record makes the limits of secondary testing and planning visible. An unadjusted secondary comparison and a sample-size illustration based on its observed effect do not establish the original design's power or resolve the primary question. The original sample-size justification, multiplicity approach, and detailed missing-data strategy are not reported in the registry record. These omissions matter because they shape how confidently readers can interpret estimates, not simply whether a p-value crosses a threshold.

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 result is reported as group medians, interquartile ranges, and a p-value, without a confidence interval or effect estimate for the between-group contrast. That leaves the precision and range of plausible primary differences unclear. The record also does not provide the underlying participant-level distributions, so the assumptions relevant to interpreting the Wilcoxon test as a median comparison cannot be evaluated from the posted summaries.

Missing data are acknowledged for the primary endpoint, with 2 continuous infusion participants and 1 intermittent bolus participant excluded from analysis for that reason. The reason for missingness and the handling method are not reported. The analysis population is not defined, and the registry does not explain the relationship between the total enrollment of 120 and the primary analysis counts of 44 and 52 beyond the stated missing-data note.

The intervention descriptions include the medication combination and administration schedules, but the full patient-controlled epidural analgesia settings are not reported in the registry record. The record also does not identify who was masked. These gaps make it harder to understand the full treatment contrast and the safeguards against bias.

Most secondary outcomes have no numerical results in the available analysis, and the registry does not report a multiplicity strategy. The hypotension calculation is unadjusted, while the posted planning illustration is based on the observed hypotension effect rather than the primary endpoint or the original trial design. The original sample-size justification, interim analyses, statistical analysis plan, and protocol-level analysis details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Programmed Intermittent Bolus Dosing Versus Continuous Epidural Infusion for Epidural Analgesia in Abdominal Surgery. — NCT03307174.
• Registry record last updated 2020-05-12; status last verified 2020-04.
• Results first posted 2020-05-12.
• 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

NCT03307174 is a completed, randomized, single-masked, parallel-group phase 4 trial sponsored by the University of California, San Francisco. The registry records 120 participants enrolled, a start date of 2016-04-14, and a primary completion date of 2019-02-28. It compares continuous epidural infusion with programmed intermittent epidural boluses for epidural analgesia in abdominal surgery.

The primary endpoint is total local anesthetic consumed during the first 24 hours. The posted analysis reports medians of 126 mg for continuous infusion and 123 mg for intermittent bolus, with interquartile ranges of 120 to 134 mg and 115 to 136 mg, respectively. The Wilcoxon (Mann-Whitney) test has p = 0.74. The registry also lists secondary outcomes, including pain, opioid consumption, satisfaction, and hypotension, but numerical results for most are not reported in the registry record.

Important analysis details—including the primary contrast interval, analysis-population definition, missing-data method, and multiplicity approach—are not reported in the registry record.