A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery (NCT04015908), a randomized phase 4 study. The primary outcome is Amount of Pain Experienced.

2. Clinical Question

The trial asks whether a combination of non-opioid analgesics, with oxycodone available for breakthrough pain, changes the amount of pain reported after ambulatory surgery compared with a Percocet regimen. The registry describes reducing or eliminating the need for opioids as the primary objective, but the posted primary endpoint is cumulative pain rather than opioid use. Amount of oxycodone used is listed as a secondary outcome.

The comparison therefore concerns two medication strategies, including their stated instructions for use, rather than a comparison of a single drug with no treatment. The registry record does not report whether participants followed the assigned medication instructions as planned, or whether use of additional analgesics was permitted.

3. Trial Design

This was a randomized, parallel-group trial listed as Phase 4. The registry lists no masking. It reports an enrollment of 100 and describes two groups: Multi-modal and Control. The Multi-modal group included 50 participants in the primary outcome results, and the Control group included 49. The registry record does not explain the difference between the enrollment figure and the group counts in the posted primary outcome.

The multimodal arm combined celecoxib, acetaminophen and pregabalin on a regular schedule, with oxycodone available as needed for breakthrough pain. The control arm was described as a 7 day supply of Percocet, also taken as needed. These are the regimens as described in the registry; information about adherence, treatment changes, or actual medication consumption is not reported in the registry record.

The registry lists the study start as 2019-08-01, primary completion as 2023-01-31, and status as COMPLETED. The sponsor is University of Utah. Details of the randomization sequence, allocation concealment, eligibility criteria, sites, and participant flow are not reported in the registry record. Although the trial is randomized, the registry does not describe the process used to generate or implement assignments. With masking listed as NONE, participants and study personnel were not masked according to the registry classification; other details about who knew group assignments are not reported.

The primary outcome was amount of pain experienced, measured cumulatively over six postoperative days. Nausea, itching and amount of oxycodone used were listed as secondary outcomes. The registry record lists four outcome measures but does not post quantitative results for the secondary outcomes in this record. It lists no analyses. That limits the available basis for judging the trial’s results beyond the descriptive primary outcome values and the posted safety counts.

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

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: Participant characteristics and anesthetics drugs

6. Primary Endpoint

The registry lists the primary outcome as Amount of Pain Experienced, measured over Cumulative every day after 6 days post-operative.

The primary endpoint is the amount of pain experienced, measured with a 0-10 Visual Analog Scale (VAS), where 0 is the lowest score and 10 is the highest. The registry explains that 10 represents severe pain and 0 represents none. It describes cumulative scores as the absolute sum of pain scores over 6 days, with a total possible range of 0-60. The reported summary is the median and inter-quartile range for each group.

A cumulative score is intended to represent pain across a period rather than pain at only one assessment. In general, repeated measurements can capture how a symptom varies over time, while a cumulative summary condenses those measurements into one value. That summary can be useful for comparing overall reported pain between groups, but it does not preserve the timing of pain within the period. Participants could have different patterns of daily scores and still have similar totals.

The registry’s timeframe is worded as “Cumulative every day after 6 days post-operative,” while the endpoint description says that scores are totals over 6 days. The record does not further clarify the daily collection schedule or how missing daily measurements were handled. No subscales were used. The scale is patient-reported, so interpretation also depends on how consistently the scale was administered and completed; those procedures are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the primary outcome as a median with an inter-quartile range. This is a descriptive summary: the median identifies the middle of the ordered observed values, while the inter-quartile range describes the interval between the first and third quartiles. Such summaries are often useful for outcome distributions that may be skewed or contain values far from the center. They do not, on their own, quantify the uncertainty in a difference between randomized groups.

What can the reported summaries establish?

The posted values describe the observed cumulative pain scores in each group. They do not provide an estimate of the distribution of the between-group contrast, a confidence interval, or a test of a null hypothesis. Comparing medians informally is not equivalent to a formal statistical comparison. The registry record lists no analyses, so the method used or intended for a primary group comparison is not reported in the registry record.

In general, a confidence interval presents a range of values compatible with the data and a specified statistical procedure. It communicates uncertainty in an estimate; a narrow interval indicates greater precision than a wide interval, under the assumptions of the procedure. No confidence interval for the treatment contrast is posted for this endpoint. The inter-quartile ranges should not be read as confidence intervals because they describe participant-level spread, not uncertainty around the group contrast.

Why might an analysis account for the outcome distribution?

In general, the choice of method depends on the outcome scale, its distribution, study design and analysis objective. A median-based summary does not reveal whether the observed values were symmetric, skewed or concentrated at particular scores. Methods can target different quantities, such as a difference in means, a difference in medians, or a broader shift in outcome distributions. Those quantities are not interchangeable. The registry does not report a statistical method or estimand for the primary comparison, so the intended target of inference is not reported in the registry record.

In general, over-dispersion means that the variability in observed data is greater than a model assumes. When a model understates variability, its uncertainty estimates can be too small and its confidence intervals or tests can be misleading. This is a general statistical consideration, not a documented feature of this trial’s analysis. The registry record does not report a model, residual checks, distributional assessment or over-dispersion adjustment.

How should the planning illustrations be understood?

Planning illustrations based on the observed effect are not the trial’s design justification and are not observed power. The registry states that the illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. They are hypothetical planning calculations. The sample size justification used when designing the trial is not reported in the registry record. No sample-size illustration should be interpreted as evidence that the trial had a particular probability of detecting an effect after the data were collected.

In general, power calculations depend on assumptions about the effect to detect, variability, analysis method, significance threshold and allocation. If those assumptions do not match the actual trial or the analysis ultimately used, a planning calculation may not describe the study’s ability to answer its question. Calculations based on the observed result are especially not a substitute for a prespecified design calculation, because the observed effect is itself uncertain. The registry does not report a prespecified effect size or planning assumptions beyond those attached to the planning illustrations.

What is missing for a full statistical appraisal?

The analysis population, handling of missing scores, prespecified analysis model, adjustment variables, and treatment of protocol deviations are not reported in the registry record. Nor are details of any interim analyses or a statistical analysis plan. Those omissions matter because analysis choices can affect the estimate and its uncertainty. Without the planned and performed methods, the posted descriptive summaries cannot be connected to a complete inferential analysis.

Randomization can help balance prognostic factors on average, but it does not guarantee balance in a particular sample. In general, an analysis should respect the randomized design and clearly state which participants and measurements it includes. The record does not describe whether results were analyzed according to assigned groups, whether participants were excluded after randomization, or how repeated daily pain measurements were combined if observations were incomplete. These are unresolved methodological details, not evidence that a particular approach was or was not used.

10. Multiplicity, Missing Data and Analysis Populations

Three secondary outcomes are listed: amount of nausea experienced, amount of itching experienced, and amount of oxycodone used. The registry record does not post quantitative results for those outcomes. It also lists four outcome measures overall and no analyses. Whether the secondary outcomes were collected, whether results were analyzed, and whether any results were omitted from this registry record are not reported in the registry record.

Multiplicity arises when several outcomes or comparisons are tested. In general, as the number of statistical tests increases, the chance of at least one apparently notable result can increase if no adjustment or prespecified hierarchy is used. Trial protocols may address this by defining a primary outcome, specifying a testing sequence, or adjusting inference. A multiplicity plan is not reported in the registry record, so it is not possible to determine what approach was planned or whether one was used.

Missing-data handling is also not reported. The primary outcome counts are 50 in the Multi-modal group and 49 in the Control group, while the registry enrollment is 100. The record does not explain the participant accounting, the availability of daily scores, or whether any primary outcome values were missing. It does not state whether missing observations were excluded, imputed, or handled by another method. No conclusion about the reasons for the group counts or the impact of missing data can be drawn from the posted record.

The analysis population is not reported in the registry record. In general, an intention-to-treat analysis retains participants in their randomized groups, while other analysis populations may apply different inclusion rules. The record does not say which population was used or whether there were exclusions after randomization. It also does not report an analysis plan, interim analyses, or protocol deviations. These gaps limit assessment of whether outcome reporting and analysis followed a prespecified approach.

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 posted serious adverse event figures list 0 serious events among 50 participants at risk in the Multi-modal group and 0 among 49 participants at risk in the Control group. The record also lists 0 other adverse events in each group and 0 deaths in each group. These are the counts recorded in the registry, not proof that no adverse experience occurred outside the definitions, observation period or reporting process used for this record.

In general, a zero count in a trial does not demonstrate that an event is impossible or that the underlying risk is zero. The ability to characterize uncommon events depends on the amount and duration of observation, as well as how events are collected and classified. The registry does not report the safety observation period, event definitions, severity criteria, relatedness assessments, or detailed ascertainment procedures. The posted counts therefore have limited scope for assessing safety beyond the recorded event categories and participant counts.

No serious adverse event terms are listed. The record does not provide additional narrative about adverse events or explain whether any events were reviewed but not posted. These counts should be read as a report of recorded events in the registry, not as a comparative statistical safety analysis.

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

The registry’s primary outcome summaries describe cumulative pain scores in two randomized groups. The Multi-modal group’s median was 28 (inter-quartile range 14 to 35), and the Control group’s median was 35 (inter-quartile range 28 to 41). These values characterize the recorded observations; they do not establish a statistically reliable difference because no inferential analysis or uncertainty interval for the comparison is reported.

The result does not quantify opioid sparing. Amount of oxycodone used was listed as a secondary outcome, but its result is not reported in the registry record. The trial objective refers to reducing or eliminating opioid need, yet the posted primary result measures pain. Thus, the reported pain summaries cannot be used to determine the amount of opioid medication used in either group or to compare opioid consumption.

The result also does not show that one regimen caused a particular pain outcome with a known degree of certainty. The study is described as randomized, which is relevant to comparisons, but details about allocation, adherence, analysis population, missing data and the statistical plan are not reported. No clinically important difference threshold is reported either. Statistical uncertainty and the clinical meaning of the observed summaries cannot therefore be fully judged from this record.

In general, a trial result is best interpreted in relation to its design, endpoint, analysis, uncertainty and completeness of reporting. Here, the registry supports a descriptive account of the posted primary pain scores and adverse event counts. It does not support a definitive claim about efficacy, opioid reduction, or comparative safety. The absence of posted secondary analyses is an information gap; it is not evidence that the secondary outcomes were equal between groups or that no differences occurred.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between the objective named in a trial record and the endpoint for which results are posted. The objective concerns whether a combination of non-opioid analgesics can reduce or eliminate opioid need after ambulatory surgery, while the reported primary outcome is cumulative pain. Opioid use is listed separately as a secondary outcome, but no quantitative result for it is reported. Keeping those outcomes distinct prevents a pain summary from being mistaken for an opioid-consumption result.

The registry also illustrates why descriptive summaries and inferential comparisons answer different questions. Group medians and inter-quartile ranges show the observed score distributions in a compact form. Without an analysis estimate and its uncertainty, they do not establish whether a difference is statistically distinguishable from variation that could occur by chance. This is particularly important when an endpoint is a cumulative patient-reported score and the analysis details are not posted.

Randomization is an important design feature, but statistical interpretation also depends on how assignment was implemented, how outcomes were collected, who was included in analysis, and how missing data and multiple outcomes were handled. Those details are not reported in the registry record. This example therefore shows how a record can provide a clear treatment contrast and descriptive endpoint values while leaving key parts of the inferential assessment unresolved.

The safety counts likewise demonstrate the limits of zero-event summaries. Zero recorded events in the reported categories is a factual description of the posted counts, but does not by itself characterize all possible safety outcomes or quantify uncertainty. A statistically careful reading separates what is directly reported from what would require additional methods and data.

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.

Several trial-specific limitations of interpretation arise from what is and is not reported. The registry gives an enrollment of 100, while the primary outcome groups contain 50 and 49 participants. It does not explain this accounting or report a participant flow diagram. The reasons for the difference, if any, are not reported in the registry record.

The outcome timeframe has imprecise wording: it is listed as “Cumulative every day after 6 days post-operative,” while the description states that pain scores were summed over 6 days. The record does not clarify the exact assessment schedule, the timing of each score, or the handling of uncompleted assessments. These details affect how the cumulative endpoint should be understood.

The trial is listed as randomized and with no masking, but the randomization procedure, allocation concealment and outcome collection procedures are not reported. Since pain is self-reported, the absence of masking is relevant to interpretation, although the record does not establish whether it changed reporting. The record does not report adherence, crossover, additional medications, protocol deviations, eligibility criteria or the analysis population.

Only descriptive primary outcome summaries and safety counts are posted. No inferential analysis, confidence interval, p-value, secondary outcome results, missing-data method, multiplicity approach, or statistical analysis plan is reported. A clinically important difference and the original sample-size justification are also not reported. These gaps prevent a complete evaluation of precision, robustness, and the alignment between planned and reported analyses. They do not establish that the trial was poorly conducted; they limit what can be concluded from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery — NCT04015908.
• Registry record last updated 2024-07-08; status last verified 2024-05.
• Results first posted 2024-07-08.
• 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 record describes NCT04015908, a completed, randomized, parallel-group Phase 4 trial sponsored by University of Utah. It lists 100 participants, no masking, and a comparison of a multimodal regimen with a Percocet control regimen after ambulatory surgery. The primary outcome is cumulative pain measured with a 0-10 Visual Analog Scale over 6 postoperative days.

The primary results report medians and inter-quartile ranges: 28 (14 to 35) for Multi-modal, with 50 participants, and 35 (28 to 41) for Control, with 49 participants. The record lists nausea, itching and oxycodone use as secondary outcomes but does not post their results. It lists 0 serious adverse events, 0 other adverse events and 0 deaths in each group.

No analyses are listed. Inferential results, missing-data procedures, analysis populations, multiplicity methods and the statistical analysis plan are not reported in the registry record. The posted values therefore support a descriptive account, but not a complete statistical comparison.