Opioid-Free Anesthetic for Tonsillectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Opioid-Free Anesthetic for Tonsillectomy (NCT04528173), a randomized phase 4 study. The primary outcome is Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score.

2. Clinical Question

The trial asked whether an opioid-free anesthetic approach for tonsillectomy was non-inferior to traditional opioid-containing anesthetic care, as described in the registry summary. The primary outcome was mean FLACC pain score during recovery, with higher scores indicating worse outcomes. The registry record does not report the observed pain scores, a comparison between groups, or a conclusion about non-inferiority.

3. Trial Design

The registry describes a prospective, randomized, parallel-group trial with triple masking. It is listed as Phase 4 and was sponsored by Children's Hospital of Philadelphia. Enrollment was 35. The record gives a start date of 2020-07-22 and a primary completion date of 2023-08-22; its status is terminated. A reason for termination is not reported in the registry record.

The comparison was between an opioid-free anesthetic approach and traditional care that included opioids. The Opioid-Free Group was described as receiving institutional standard clinical care without opioids, including dexmedetomidine and ketorolac. The Traditional Care Group was described as receiving a standardized opioid dose at the beginning of the case and again at the end if needed. The record names ketorolac, dexmedetomidine, morphine, and fentanyl among the interventions. It does not report the specific opioid, dose, or use pattern for each participant.

Randomization can reduce systematic differences between treatment groups on average, while masking can limit some sources of bias in outcome assessment and care. Those are general design principles; the registry record does not describe the randomization sequence, allocation concealment, or which roles were masked. It also does not explain how triple masking was implemented.

The traditional-care arm description ends mid-sentence after stating that dexmedetomidine and ketorolac would not be used intra-operatively in that cohort. Further clarification of the planned distinction between groups is not reported in the registry record. Nor does the record give the reason for the terminated status or describe whether termination affected enrollment, follow-up, or analysis. These gaps make it difficult to assess whether the trial was completed as intended.

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: Nurse maximum pain score not documented for 2 subjects

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 Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score, measured over up to 1 hour.

The primary endpoint is the mean FLACC (Face, Legs, Activity, Cry, Consolability) pain score, reported on a scale from 0 to 10. The registry says scores were assessed by a blinded study-team observer at 15 and 30 minutes after awakening. It also describes a nursing maximum FLACC score obtained by an unblinded patient Registered Nurse during the Post-Anesthesia Care Unit stay, within one hour of awakening, using nursing documentation in the electronic medical record. Higher scores indicate worse outcomes.

FLACC is a behavioral pain assessment, with the score reflecting the listed domains rather than a participant’s verbal rating alone. In general, repeated assessment during recovery can describe pain at different points, while a maximum score can capture the highest documented pain during the specified period. These are distinct summaries and can answer different questions. The registry record does not explain how the observer assessments and the nursing maximum were combined or prioritized for the primary analysis.

The registry identifies the outcome as a mean with standard deviation, but does not report group means, standard deviations, an estimated between-group difference, or a confidence interval. It notes that the nurse maximum score was not documented for 2 subjects. The handling of those missing scores is not reported in the registry record. Without the outcome values and a clearly specified comparison, the relative pain experience in the groups cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. The endpoint is a FLACC score, on a scale from 0 to 10, with higher scores indicating worse outcomes. The record does not report an inferential analysis of this outcome. The explanations below describe general statistical principles relevant to the stated design; they are not a description of analyses documented for this trial.

What does a mean summarize?

In general, a mean describes the center of a set of numerical observations by averaging their values. A standard deviation describes how spread out individual observations are around that mean. Means can be useful for comparing groups, but they do not show the full distribution: participants may have different scores even when group means are similar. For a bounded score such as FLACC, interpretation also depends on where observed scores fall on the scale and how the score was collected.

The registry describes observer assessments at 15 and 30 minutes after awakening and a nursing maximum during the recovery stay within one hour. A mean over repeated assessments, a mean at a specified assessment time, and a mean of individual maximum scores are not interchangeable summaries. The record does not specify which of these was the primary analysis quantity or how measurements from different sources were combined. The observer was described as blinded; the nurse obtaining the maximum score was described as unblinded.

What would a between-group estimate mean?

In general, a comparison of group means estimates the difference in average scores under the trial’s assigned approaches. A confidence interval expresses uncertainty around such an estimate: it identifies a range of values reasonably compatible with the data and analysis assumptions. A narrow interval indicates greater precision than a wide interval, but precision alone does not determine clinical importance. Neither a mean difference nor a confidence interval for this endpoint is reported in the registry record.

A p-value, when used, describes how compatible the observed data are with a specified statistical null model; it is not the probability that a treatment has no effect. A p-value also does not show whether an observed difference is important or whether a non-inferiority requirement has been satisfied. The registry record does not report a p-value for the primary outcome or state the planned hypothesis-testing procedure.

How does non-inferiority differ from a usual difference test?

In general, a non-inferiority trial tests whether the outcome under an intervention is not worse than the comparator by more than a prespecified acceptable margin. The margin must be defined before interpreting the results and should be justified for the clinical question. A confidence interval for the treatment contrast is commonly evaluated relative to that margin. A conventional test that finds no statistically significant difference does not, by itself, demonstrate non-inferiority. The registry record describes the objective as non-inferiority but does not report a margin, its justification, or the analysis used to assess it.

Randomization is intended to support a fair comparison by assigning participants to groups through chance. In general, random assignment helps balance measured and unmeasured characteristics over repeated use of the process, but it does not guarantee exact balance in a particular trial. The record says the study was randomized but does not describe the sequence-generation method, concealment of assignment, or any adjustment for baseline characteristics.

Why can repeated or over-dispersed data matter?

General statistical methods must account for the structure of the data. Repeated scores from the same participant tend to be related, so treating each score as independent can understate uncertainty. A model for repeated observations can represent within-participant correlation, but the registry record does not report whether such a model was planned or used. Over-dispersion, in general, occurs when observed variability is greater than a statistical model assumes; ignoring it can make uncertainty estimates too small. No model details or variability diagnostics are reported for this trial.

The nursing maximum and observer assessments also differ in collection method and masking. In general, differences in measurement procedures can affect comparability and should be reflected in the outcome definition and analysis plan. The record does not say whether the nurse maximum was a separate outcome, a replacement for observer scores, or part of a combined primary summary.

What do the planning illustrations represent?

The registry record describes sample-size illustrations as planning calculations based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that such illustrations are not the trial’s own design calculation. In general, planning estimates depend on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. They are not observed power and do not establish that the trial had adequate power. The record does not report a sample-size justification used to design this trial or a numeric effect estimate from which to evaluate the illustrations.

The record also does not report model diagnostics, covariate adjustment, an interim-analysis plan, or sensitivity analyses. Those methods cannot be inferred from the randomized design or from the non-inferiority objective.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and names secondary outcomes concerning nausea, vomiting, or pruritis; unplanned medical attention; hospital readmission; oxygen saturation below 90% for more than 30 seconds when non-artefactual; rescue opioid use; family satisfaction on a five-point Likert score; and postoperative bleeding. The primary FLACC outcome is described at multiple assessment times and also includes a nursing maximum score. The record does not explain how those measures or time points were prioritized for analysis.

When a study evaluates multiple outcomes or multiple time points, general statistical practice considers the possibility of chance findings from repeated testing. A prespecified hierarchy or adjustment can help control that issue, but the multiplicity strategy is not reported in the registry record. The record does not report analyses for the listed outcomes.

For missing data, the registry notes that nurse maximum FLACC scores were not documented for 2 subjects. The reason for missingness, the treatment of these observations, and any sensitivity analysis are not reported in the registry record. Missing measurements can affect a group comparison if their absence is related to the outcome or differs across groups; that is a general concern, not a conclusion about this trial.

The analysis populations, such as whether results were to be analyzed by randomized assignment or according to treatment received, are not reported in the registry record. Participant flow, protocol deviations, and details of withdrawals or loss to follow-up are also not reported. With no primary or secondary analysis results posted, the extent to which missingness or analysis choices affected the estimates cannot be evaluated.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: prolonged admission (5.6%), readmission (5.6%), bleeding events (0.0%).

The registry reports serious adverse-event counts by group. In the Traditional Care Group, 2 of 18 participants at risk were listed as affected by serious adverse events; in the Opioid-Free Group, 0 of 17 were listed as affected. The corresponding other-adverse-event counts were 4 of 18 and 6 of 17. Deaths were recorded as 0 in each group.

The record lists prolonged admission and readmission as top serious-event terms, each with 5.6%, and bleeding events with 0.0%. These percentages are presented as registry entries; the record does not specify their group attribution in the information available. They should not be assigned to an individual group without that detail. The term list also does not provide event-level timing, severity grading, or a causal assessment for each event.

These figures are descriptive. In general, small event counts can be unstable, and differences in counts do not by themselves establish that an anesthetic approach caused or prevented an event. The registry record does not report a statistical comparison of adverse events or additional details needed to assess comparative safety. The counts should therefore be read as reported, not as proof of a safety advantage or disadvantage.

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

The registry record establishes that the study was designed to compare an opioid-free anesthetic approach with traditional opioid-containing care for tonsillectomy. It describes randomization, triple masking, a parallel-group design, and a primary outcome based on FLACC pain scores during recovery. It also reports some adverse-event counts. These details clarify the intended research question and how the outcome was to be assessed.

The record does not provide the primary pain-score results or an inferential comparison. It therefore cannot show whether the groups had similar or different mean scores, how precise a comparison would be, or whether the stated non-inferiority objective was met. The non-inferiority margin and statistical analysis plan are not reported in the registry record, so the standard for interpreting such a conclusion is also unavailable.

The study’s terminated status does not, on its own, explain why it ended or establish what effect termination had on the evidence. The record does not report the reason, the analysis population, or the handling of the missing nurse maximum scores. These omissions limit assessment of completeness and potential bias. Enrollment does not substitute for a reported analysis or establish how many observations contributed to the primary outcome.

The adverse-event entries provide descriptive information but do not establish a causal comparison. The counts do not answer the primary pain question, and no comparative safety analysis is reported. Likewise, the existence of planning illustrations cannot establish observed power or a definitive interpretation of the findings.

In general, a clinical trial’s statistical conclusion depends on the actual outcome estimates, uncertainty, analysis choices, and fit between the analysis and the prespecified objective. For this record, the appropriate interpretation is limited: the design and endpoints are described, but the posted information does not report the primary results needed to determine what the trial observed about recovery pain or non-inferiority.

13. Why This Trial Matters Statistically

This trial raises a statistical question that differs from asking whether two groups have statistically distinguishable outcomes. Its stated aim was non-inferiority: whether an opioid-free approach could avoid an unacceptable worsening in recovery pain relative to traditional opioid-containing care. As a general matter, answering that question requires a clearly defined margin and an estimate precise enough to evaluate the margin. Neither the margin nor the primary comparison is reported in the registry record.

The endpoint also illustrates why outcome definitions matter. Observer FLACC scores were described at 15 and 30 minutes after awakening, while a nurse-recorded maximum was collected during the recovery stay within one hour. Those summaries can represent different features of pain. A clear primary estimand—the precise outcome, time point, population, and treatment contrast being targeted—is important when several measures could be called the primary endpoint. The registry record does not explain how these measurements were reconciled.

Masking and randomization are important design features, but they do not replace transparent reporting of analysis methods and results. The record says the trial was randomized and triple masked, yet does not report how masking was implemented or how the primary comparison was analyzed. Such details matter when interpreting subjective or observer-assessed outcomes and when evaluating the risk of bias.

Finally, the terminated status and absence of posted analyses make completeness a central interpretive issue. The record describes the intended comparison and some safety counts, but leaves the core statistical result unavailable. This is a useful reminder that a registered objective, even in a randomized design, is not itself evidence that the objective was achieved or that a treatment comparison supports a particular conclusion.

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 main limitation for interpreting this trial is that the registry record does not report the primary outcome results or any analysis results. It gives no group means or standard deviations for FLACC scores, no estimated contrast, and no confidence interval or p-value. Consequently, the intended comparison cannot be evaluated from the posted record.

The record describes a non-inferiority objective but does not report the non-inferiority margin, how it was selected, or the statistical procedure used. The detailed endpoint description includes observer assessments at 15 and 30 minutes and a nursing maximum within one hour, but does not state how these measures were combined or which summary was used for the primary comparison. The nurse maximum was not documented for 2 subjects, and its missing-data handling is not reported.

The study is marked terminated, but the reason and consequences are not reported in the registry record. The record does not provide participant flow, analysis populations, treatment adherence, protocol deviations, or details of missingness beyond the nurse-score note. It also does not report the randomization procedure, allocation concealment, the roles included in triple masking, or the statistical analysis plan.

The description of the Traditional Care Group ends mid-sentence. Although the record names ketorolac, dexmedetomidine, morphine, and fentanyl, it does not specify participant-level drug use or doses. Safety data are limited to summarized counts and listed serious-event terms, with no reported comparative analysis or event-level context. These limitations leave important aspects of outcome interpretation, treatment delivery, and trial completion unresolved.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Opioid-Free Anesthetic for Tonsillectomy — NCT04528173.
• Registry record last updated 2024-12-20; status last verified 2024-12.
• Results first posted 2024-12-20.
• 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 Phase 4, randomized, triple-masked, parallel-group trial sponsored by Children's Hospital of Philadelphia. It compared an opioid-free anesthetic approach including dexmedetomidine and ketorolac with traditional care that included opioids for tonsillectomy. The primary outcome was mean FLACC pain score during recovery, with higher scores indicating worse outcomes. The trial is listed as terminated, and the record does not report why it ended.

Although the record describes the primary outcome and several secondary outcomes, it reports no analysis results. The primary scores, between-group estimate, uncertainty, non-inferiority margin, analysis plan, and missing-data methods are not reported in the registry record. Some serious and other adverse-event counts are listed, but they are descriptive and do not establish a comparative treatment effect. The available record therefore describes the intended study and selected safety data without answering its primary statistical question.