Comparing Five Oral Analgesics for Treatment of Acute Pain in the Emergency Department (ED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Five Oral Analgesics for Treatment of Acute Pain in the Emergency Department (ED) (NCT03173456), a randomized phase 2 study. The primary outcome is Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline.

2. Clinical Question

3. Trial Design

This completed phase 2 study is registered as NCT03173456 and is titled “Comparing Five Oral Analgesics for Treatment of Acute Pain in the Emergency Department (ED).” Its official title specifies acute musculoskeletal extremity pain in the emergency department. The registry records Albert Einstein College of Medicine as sponsor, a start date of 2017-11-28, a primary completion date of 2019-11-14, and enrollment of 600.

The design is randomized, quadruple-masked, and parallel-group. Five medication regimens were compared: 400 mg ibuprofen + 1000 mg acetaminophen; 800 mg ibuprofen + 1000 mg acetaminophen; 30 mg codeine + 300 mg acetaminophen; 5 mg hydrocodone + 300 mg acetaminophen; and 5 mg oxycodone + 325 mg acetaminophen. The registry does not report the allocation ratio or the specific roles covered by quadruple masking.

The primary outcome was change in pain score from baseline to one hour after medication. The posted group summaries include 120 participants for 400 mg ibuprofen/APAP, 118 for 800 mg ibuprofen/APAP, 120 for codeine/APAP, 119 for hydrocodone/APAP, and 120 for oxycodone/APAP. These are outcome-specific counts; the registry does not explain the difference between the recorded enrollment and the counts contributing to this endpoint.

Secondary outcomes cover rescue medication during the two-hour period, willingness to take the study medication again at the end of that period, and side effects within one hour and within two hours after ingestion. A further secondary outcome concerns change in pain through two hours. The registry record does not report the study’s sample-size justification or detailed protocol procedures.

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.

Baseline

Reasons for not completing this period:

2 Hour Follow-up

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: The 3 patients assigned to treatment arms did not provide any data because of malfunctioning of the medication dispensing system.

6. Primary Endpoint

The registry lists the primary outcome as Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline, measured over Prior to Ingestion of study medication to one hour after ingestion of the study medication.

The primary endpoint is the change in pain intensity from before medication to one hour after ingestion. Pain was measured on an 11-point Numerical Rating Scale, with 0 meaning no pain and 10 meaning the worst possible pain. Change was calculated as the baseline score minus the one-hour score. Under that definition, a larger positive change represents a larger reduction in the recorded pain score.

The registry reports the mean change in each group, with a 95% confidence interval. The reported means are 3.0 for 400 mg ibuprofen/APAP, 3.0 for 800 mg ibuprofen/APAP, 3.4 for codeine/APAP, 3.1 for hydrocodone/APAP, and 3.3 for oxycodone/APAP. Their respective 95% confidence intervals are 2.6 to 3.5, 2.5 to 3.5, 2.9 to 3.9, 2.7 to 3.5, and 2.8 to 3.7.

A mean summarizes the average change in scores, while the confidence interval conveys uncertainty around that estimated mean. The interval is not a range containing every individual participant’s change. The registry uses change in pain score to compare how much scores shifted over the specified period; it does not by itself describe other features of the pain experience or outcomes beyond the measured time points. The outcome description says that a higher score is the better outcome, but the registry record does not report a threshold for a clinically important change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s recorded change is a numerical score, and the registry presents a mean for each treatment group. A mean is useful for describing the average score change, but it does not show how widely individual changes varied. The registry reports confidence intervals rather than a measure of within-group spread, so the posted summaries do not describe the full distribution of scores.

What does the confidence interval convey?

In general, a confidence interval describes the uncertainty associated with an estimate under the assumptions of the method used to construct it. A narrower interval indicates greater precision for that estimate than a wider interval. These intervals concern each group’s mean change; they are not prediction intervals for individual participants, nor do they directly quantify the uncertainty in every possible between-group contrast. The registry identifies the intervals as 95% confidence intervals but does not report further details about their calculation.

What does the reported analysis of variance test?

In general, analysis of variance evaluates whether the data are compatible with equal group means, against an alternative in which at least one mean differs. The reported p-value of 0.69 is for the five-group primary analysis. A p-value measures how compatible the observed data are with the null model and the test assumptions; it is not the probability that the null hypothesis is true. A result that does not provide evidence against equal means cannot prove equality. The registry does not report the model specification, any covariate adjustment, or checks of the assumptions used for this analysis.

Why are there no recalculated primary pairwise results?

Recalculated comparisons labeled as such are simple, unadjusted calculations from posted summary statistics. For this continuous primary outcome, the record does not contain the information needed to estimate two-group comparisons from those summaries, so these comparisons are not estimable. The sponsor’s reported five-group analysis remains the primary inferential result. A two-group calculation, where available for a secondary outcome, would answer a narrower question and would not replace an overall test across all five regimens.

How should the binary secondary outcomes be read?

Rescue medication, willingness to take medication again, and side-effect outcomes are recorded as participant counts. A risk difference compares the observed event proportions between two groups; the accompanying confidence interval describes uncertainty in that difference. In general, an interval spanning zero is compatible with both a difference in either direction and no difference. The recalculated comparisons are unadjusted, so their p-values do not account for multiple outcomes, multiple pairwise comparisons, or any other analysis choices. They are exploratory descriptions of the posted counts, not a complete replacement for the trial’s planned analysis.

The registry also reports whole-group chi-squared tests for rescue medication and side effects within one hour. These tests assess whether the observed categorical outcome distributions differ across the groups, subject to the test’s assumptions. The record does not give an overall reported test for the willingness-to-take-again outcome or for side effects within two hours. The absence of a posted test is not evidence of no difference.

What do planning illustrations mean?

Planning illustrations use the observed effect as a reference and show hypothetical participants per arm for specified fractions of that effect and target power levels. They are not observed power, do not describe the study’s original design calculation, and should not be interpreted as proof that the trial was adequately or inadequately powered. The stated calculation assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The sample-size justification used when the trial was designed is not reported in the registry record.

For binary outcomes, the observed effect used in such an illustration is based on the posted event counts and group sizes. Estimates from a study can be uncertain, so planning based on an observed effect is illustrative rather than a reliable prediction of a future study’s requirements. The record does not report whether any adjustment for missing data or other design features was incorporated into those illustrations.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as an analysis of variance across the five groups, with p = 0.69. This is the relevant reported inferential result for the primary endpoint. The posted group means and confidence intervals describe the observed one-hour pain-score changes, while the overall analysis tests the group comparison. The two forms of information serve different purposes: estimates describe the observed outcomes, and the test evaluates the overall contrast under its analysis assumptions.

No recalculated two-group primary comparisons are available from the posted continuous-outcome summaries. They therefore cannot be used to challenge or replace the sponsor’s analysis. The record does not identify a discrepancy between the sponsor result and a recalculation. For secondary outcomes, recalculated comparisons are simple and unadjusted; they are not necessarily the sponsor’s planned analyses. The registry separately reports whole-group chi-squared tests for rescue medication and side effects within one hour. Those reported tests should be distinguished from the selected two-group recalculations.

The record does not report a more detailed statistical analysis plan, including whether additional adjustment or model-based analyses were performed. As a result, interpretation should stay with the analyses actually reported: the primary five-group analysis and the posted secondary results, without treating unadjusted recalculations as confirmatory evidence.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary endpoint, and five posted secondary outcomes. Considering multiple outcomes and comparisons raises a multiplicity question: when many statistical tests are examined, some may appear notable by chance even if there is no underlying difference. The record does not report whether the investigators prespecified a hierarchy of outcomes, selected a subset for confirmatory testing, or adjusted p-values or confidence intervals for multiple comparisons.

The primary analysis is reported as one overall analysis of variance across the five groups. The registry also gives whole-group chi-squared tests for some secondary outcomes and selected two-group recalculations for others. These are not interchangeable analyses. The recalculated comparisons are unadjusted, and the record does not report whether they were planned in advance. The secondary results should consequently be interpreted with caution rather than as a collection of independent confirmatory tests.

Outcome counts differ across measures and arms. For the primary outcome, the posted group counts range from 118 to 120; counts for secondary outcomes also vary. The registry record does not report why outcome data are unavailable for some participants, whether missingness was related to treatment or outcomes, or how missing data were handled. It does not specify whether analyses followed an intention-to-treat, per-protocol, or other population definition.

The registry also does not report details of exclusions, protocol deviations, imputation, sensitivity analyses, or the statistical analysis plan. These omissions make it difficult to assess how robust the results are to alternative assumptions about missing outcomes or analysis populations. The observed group counts should therefore be understood as the numbers contributing to the particular posted outcome summaries, not as a complete description of participant flow or analysis procedures.

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.

The registry’s adverse-event results list zero serious adverse events and zero other adverse events in each medication group, with zero deaths listed in each group. The corresponding at-risk counts are 120 for 400 mg ibuprofen/APAP, 118 for 800 mg ibuprofen/APAP, 120 for codeine/APAP, 119 for hydrocodone/APAP, and 120 for oxycodone/APAP. No serious adverse-event terms are listed.

These figures describe what is recorded in the registry for the stated adverse-event categories and at-risk groups. They should not be read as proof that no adverse events occurred in any broader sense, or as evidence that the medications have identical safety profiles. The registry separately lists secondary outcomes about side effects within one hour and within two hours; those measures are distinct from the serious and other adverse-event figures.

The record does not report detailed definitions, collection procedures, severity criteria, or follow-up beyond the specified adverse-event reporting. It also does not explain whether the zero counts reflect no events observed or another reporting process. A zero in a registry summary is therefore a statement about the posted record, not a guarantee about risk or a basis for treatment decisions.

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

The primary result describes mean change in a pain score over one hour among the five randomized groups. The reported analysis of variance, p = 0.69, does not provide evidence of a difference in mean change across those groups under the reported analysis. This finding is not proof that the groups are equal, and it does not establish equivalence or noninferiority. The registry does not report a clinically important difference threshold that would help translate the estimated score changes into a judgment about clinical importance.

The group means and confidence intervals show the estimated average changes and their uncertainty. They do not show how individual participants responded, whether some participants had much larger or smaller changes, or how outcomes evolved beyond the measured time points. The one-hour outcome is a specific measure at a specific interval; it does not by itself answer questions about longer-term pain, function, or other aspects of care.

Secondary outcomes provide additional descriptive information about rescue medication, preference, and side effects. Their differences should not be interpreted as a definitive ranking of the five regimens. Several comparisons are unadjusted, the multiplicity approach is not reported, and outcome counts vary. The registry also does not report how missing data were handled or define the analysis populations in detail.

The results therefore support a restrained reading: the posted primary analysis did not detect an overall difference in the measured one-hour mean pain-score change, while uncertainty and limitations in reporting remain. The record does not establish that all regimens have the same effects, that one regimen is preferable, or that the findings apply beyond the studied emergency-department setting and recorded follow-up. No medical advice follows from these registry results alone.

14. Why This Trial Matters Statistically

This trial is statistically informative because it compares five active medication regimens using a common continuous pain-score endpoint and a randomized parallel-group design. The primary analysis asks an overall question across the groups rather than treating each pairwise contrast as the only target. That distinction matters: an overall test and a series of pairwise comparisons answer different questions and have different implications for multiplicity.

The registry provides both group-level mean estimates with confidence intervals and an overall test. Reading these together helps separate the size and precision of the observed estimates from the statistical evidence about differences among groups. The result also illustrates why a nonsignificant test should not be treated as proof of equivalence: the record does not report an equivalence margin or a noninferiority framework.

Reporting outcomes at different time points and across pain, rescue medication, preference, and side effects offers a broader view of what was measured. At the same time, more outcomes create greater interpretive complexity. Without a reported multiplicity plan, missing-data methods, analysis-population definitions, and fuller statistical plan, secondary findings are best regarded as exploratory.

Finally, this record illustrates the limits of summary statistics. They permit description of group means and selected binary comparisons, but not reconstruction of every individual-level analysis. The sample-size illustrations based on observed effects are planning aids rather than evidence about the trial’s original design or its observed power. Careful separation of reported sponsor analyses from unadjusted recalculations is essential to keep conclusions aligned with what the registry actually documents.

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.

Several trial-specific reporting gaps limit interpretation. The registry does not report the allocation ratio, the practical details of quadruple masking, the sample-size justification, or a detailed statistical analysis plan. It does not identify the intended analysis population or explain how participants with missing outcome data were handled. The outcome-specific counts vary, but reasons for those variations are not reported.

The primary result is an overall five-group test. The record does not report pairwise primary comparisons, an equivalence or noninferiority framework, or a threshold for a clinically important difference. Consequently, the result cannot establish that the medication regimens are equivalent or rank them by clinically meaningful benefit. The group confidence intervals describe means but do not show individual variation because a measure of spread is not posted.

Multiplicity handling is not reported, despite several outcomes and comparisons. Selected recalculated secondary comparisons are unadjusted, and the registry does not identify whether they were prespecified. Whole-group tests are posted for some secondary outcomes but not all. These differences in reporting make the secondary findings harder to compare and increase the need for caution.

The record also does not provide detailed adverse-event definitions, collection procedures, or broader follow-up information. The serious and other adverse-event counts should be interpreted within the registry’s reported categories and periods. The trial’s emergency-department setting and specified time points bound the scope of the available evidence; the record does not establish how the results apply in other settings or over longer periods.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Comparing Five Oral Analgesics for Treatment of Acute Pain in the Emergency Department (ED) — NCT03173456.
• Registry record last updated 2022-02-01; status last verified 2022-01.
• Results first posted 2022-02-01.
• 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

NCT03173456 is a completed randomized, quadruple-masked, parallel-group phase 2 trial sponsored by Albert Einstein College of Medicine. The registry records enrollment of 600 and compares five oral analgesic regimens for acute musculoskeletal extremity pain in the emergency department.

The primary outcome is mean change in an 11-point pain score from baseline to one hour after medication. The reported overall analysis of variance has p = 0.69. The registry also posts secondary results concerning rescue medication, willingness to take medication again, and side effects. It does not report detailed methods for missing data, analysis populations, multiplicity, or the original sample-size justification. The posted findings describe the recorded outcomes and should not be interpreted as proving equivalence among regimens.