An Efficacy and Safety Trial of Intranasal Ketorolac in Emergency Department Patients for the Treatment of Acute Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Trial of Intranasal Ketorolac in Emergency Department Patients for the Treatment of Acute Pain (NCT01471639), a na na study. The primary outcome is Efficacy of Intranasal Ketorolac on Numeric Pain Scale.

2. Clinical Question

The study objective was to assess the efficacy, safety and tolerability of intranasal ketorolac for acute pain among adults seeking emergency department care. Statistically, the key question is descriptive: what pain-rating changes and adverse events were recorded after treatment in this enrolled group? Without a control group, changes over time cannot by themselves distinguish a treatment effect from other influences, such as the natural course of pain, expectation, or additional care received during the emergency visit. The record does not report details about other treatments or their timing. Thus, the registry supports understanding the study’s question and structure, but the posted information does not permit a precise estimate of comparative efficacy.

3. Trial Design

The registry lists this study as completed, with a prospective, open-label, nonrandomized design and a single treatment group. The intervention was intranasal ketorolac. Enrollment was 37. The start is recorded as 2011-11 and primary completion as 2012-06. The record lists phase as NA and allocation as NA. Masking is recorded as none. These features describe a study without randomized assignment, blinding, or a concurrent control group.

In a single-group study, outcomes are observed among people who receive the intervention, rather than compared with outcomes in a separately assigned control group. The design can describe what happened to participants after treatment and can record safety events. It cannot, on its own, isolate the effect of treatment from other explanations for changes over time. This limitation is especially relevant for pain ratings, which can change for reasons other than the intervention.

The primary outcome is described as change in numeric rating scale scores from baseline, with follow-up through 4 hours. The registry also lists adverse event/side effects as a secondary outcome. It records 2 outcome measures and 0 analyses, but does not describe the statistical procedures used to summarize or test the outcomes. Details of recruitment, eligibility beyond the stated age range, the treatment protocol, and the handling of follow-up are not reported in the registry record.

The registry describes the arm as intranasal ketorolac (Sprix), a single arm study. Its design fields should not be interpreted as evidence of a comparison with another treatment. The record also does not report a statistical analysis plan or a sample-size justification for the trial. Any planning illustrations based on a hypothetical two-arm design are separate from this single-group study and should not be read as its original design or as observed power.

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: Chronic pain, critical illness

Overall Study

Analysis population for the primary outcome, as defined in the registry: Improvement in pain score rating among participants rating from baseline pain scores, 20 minutes, 40 minutes, 1 hour, 2 hour, 3 hour and 4 hour post dose. Pain scale ranging from 0 (no pain) - 10 (worst possible pain)

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 Efficacy of Intranasal Ketorolac on Numeric Pain Scale, measured over up to 4 hours.

The primary endpoint concerns change in numeric pain ratings after intranasal ketorolac. The scale runs from 0, meaning no pain, to 10, meaning the worst possible pain. The record describes assessing improvement from baseline at 20 minutes, 40 minutes, 1 hour, 2 hour, 3 hour and 4 hour post dose, with a timeframe of up to 4 hours.

A numeric rating scale converts a person’s reported pain intensity into a value that can be followed over time. Repeated ratings can describe the timing and pattern of reported pain during follow-up. This is a general explanation of the measurement approach; it does not establish that a change occurred in this study. The registry does not provide the actual scores, average or other summary changes, variability, confidence intervals, or statistical tests for the primary outcome.

Because the endpoint is based on changes from baseline in a single-group study, interpretation depends on how ratings were collected and summarized, as well as on what occurred during follow-up. The record does not report whether all scheduled ratings were available, how missing ratings were handled, or whether the analysis used a particular summary across time points. Those details matter for judging the size and precision of any observed change, but they are not reported in the registry record.

The endpoint is relevant to the study’s stated aim of evaluating acute pain relief, but a measure’s relevance does not substitute for reported results. Without numerical endpoint results and their uncertainty, readers cannot assess the magnitude, consistency, or precision of pain-rating changes from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations become estimates, how uncertainty is expressed, and how comparisons are made. The registry record gives the primary outcome definition and follow-up times, but it does not report a statistical analysis plan, estimates for the primary outcome, or inferential results. The explanations below describe general statistical principles and distinguish them from methods documented for this trial.

What does a change score represent?

In general, a change score is a later measurement interpreted relative to a baseline measurement. For this study, the outcome description refers to change in numeric pain rating after dosing. A summary might describe change at each scheduled assessment, or use another prespecified approach to summarize the repeated ratings. The registry does not say which summary was used, whether the analysis was based on individual change scores, or how a result across the follow-up period would be defined.

Change scores can be useful because they relate follow-up to each participant’s starting measurement. They do not remove all sources of bias or uncertainty. For example, baseline measurement error, differences in follow-up completion, and events occurring during follow-up can affect the observed pattern. These are general considerations, not reported findings about this trial.

Why does the single-group design matter?

In general, a concurrent control group helps distinguish changes associated with receiving an intervention from changes that might have occurred without it or under another treatment. Here, the design is recorded as single-group, nonrandomized and open-label, with no masking. The record does not identify a concurrent comparator. A before-and-after description can show the course of observed ratings in the treated group, but it cannot estimate a randomized treatment contrast.

Open-label measurement can also matter when outcomes are reported by participants. Knowledge of treatment may influence expectations or how a pain rating is reported. This is a general methodological concern; the registry does not report evidence that it affected ratings in this trial. The record does not describe procedures intended to address this possibility.

What does a confidence interval communicate?

In general, a confidence interval presents a range of estimates compatible with the data and the statistical procedure used. Its width conveys precision: a wider interval indicates more uncertainty about the estimate than a narrower interval, under the method’s assumptions. An interval does not address all sources of bias, and it cannot repair the lack of a comparator. The registry does not report a confidence interval for the primary endpoint, so its precision cannot be evaluated from the posted information.

Why can repeated measurements need special handling?

Ratings taken from the same participant over time are related rather than independent observations. General approaches to repeated measures account for that within-participant relationship, whereas treating every rating as unrelated can misstate uncertainty. Methods also need to specify how the time pattern is summarized and how incomplete follow-up is handled. The registry lists assessments at 20 minutes, 40 minutes, 1 hour, 2 hour, 3 hour and 4 hour post dose, but does not report a repeated-measures model, a summary rule, or an approach to missing ratings.

How should the planning illustrations be interpreted?

The registry’s general sample-size assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These assumptions do not describe the trial’s single-group design, and the illustration is not a sample-size justification for this study. A planning sample size is not observed power. Observed power is not a substitute for reporting an estimated effect and its uncertainty.

The record does not report the trial’s own sample-size justification, a target enrollment, or an analysis plan. It does not report the numerical efficacy estimates needed to assess an effect-based planning illustration. Therefore, the illustration cannot be used to infer what the trial was designed to detect or how precisely its primary outcome was estimated.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes. If it is ignored, standard errors and confidence intervals can be too small, making results appear more precise than warranted. This is a general statistical concept. The registry does not report an over-dispersed outcome model, and the primary endpoint is described as pain-scale change rather than a count outcome. The adverse-event figures are counts, but no model-based analysis of those counts is reported.

What can be inferred from the listed analyses?

The registry lists 0 analyses. That entry does not establish that no statistical work occurred; it indicates that no analyses are listed in the record. No p-value, adjusted estimate, confidence interval, or model specification for the primary outcome is reported. Statistical interpretation should therefore remain descriptive and limited to the information actually recorded.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description involves repeated pain ratings at baseline and at multiple follow-up times through 4 hours. When several outcomes or time points are examined, general statistical practice considers whether the analysis has a prespecified primary comparison and whether adjustment or another strategy is needed to address multiplicity. The registry record does not report a testing hierarchy, multiplicity adjustment, or a method for combining repeated measurements. It is not possible to determine from the record whether the time points were analyzed separately or summarized together.

The record lists adverse event/side effects as a secondary outcome and 2 outcome measures overall. It does not provide a detailed outcome analysis plan or identify how multiple outcome tests were handled. No p-values or estimates for the primary endpoint are reported, so there is no basis for assessing the consequences of multiple testing in the posted results.

Missing-data handling is also not reported. The record does not say how many participants contributed ratings at each follow-up time, how incomplete ratings were treated, or whether any imputation or model-based approach was used. In general, missingness can affect an estimate if the availability of measurements is related to pain or other participant characteristics. The effect of missingness cannot be assessed without reporting the pattern of follow-up and the analysis approach.

The analysis population is not reported in the registry record. Enrollment of 37 does not establish that all enrolled participants contributed to each outcome analysis. The record does not describe exclusions, withdrawals, protocol deviations, or whether the efficacy analysis included all treated participants. These omissions limit the ability to assess which participants the primary outcome results would represent.

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 non-serious adverse event terms

The registry lists safety counts for the intranasal ketorolac group. Among 37 participants recorded as at risk, 0 serious adverse events and 0 deaths are listed. The record also lists 7 other adverse events among 37 participants at risk. These are event counts as recorded in the registry; they do not by themselves show how events were distributed over time or whether the same participant could contribute more than one event.

The record does not give the terms for the other adverse events, their severity, timing, duration, or assessed relationship to treatment. It also does not describe the event-collection method or the rules used to classify seriousness. The absence of a listed serious event in this group should be read as a registry count, not as proof that serious events are impossible or that risk is absent.

Because the trial has no concurrent comparator group, these figures cannot establish a comparative safety difference. A comparison would require an appropriate control group and enough detail about follow-up and event ascertainment. The registry’s counts describe reported events in the study group, while broader safety interpretation remains limited by the information not reported in the registry record.

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

The record supports a clear description of the study question: it followed pain ratings after intranasal ketorolac in emergency department patients with acute pain and recorded adverse events. It identifies a primary pain-scale outcome, a follow-up timeframe of up to 4 hours, enrollment of 37, and a single-group, open-label, nonrandomized design. It also reports counts for serious adverse events, other adverse events, and deaths.

It does not provide numerical results for the primary pain outcome. Without those results, readers cannot judge the observed magnitude or pattern of change, or how precise an estimate might be. The record also does not report an analysis plan, confidence intervals, statistical tests, or handling of missing ratings. These gaps prevent a full statistical assessment of the efficacy outcome.

Even if numerical before-and-after changes were available, the study design would not by itself show how those changes compare with what would have happened under another treatment or without the intervention. A single-group observation is descriptive and is vulnerable to influences beyond treatment. The record does not offer a concurrent control to separate those explanations.

The adverse-event counts should likewise be interpreted narrowly. They are registry-reported counts for this group, not a comparative risk estimate. The terms and additional details for the other adverse events are not reported in the registry record. The listed serious-event and death counts do not establish the absence of risk beyond the observed study record.

Accordingly, the posted information describes the trial’s design and recorded safety counts but does not establish whether intranasal ketorolac reduced pain or how its effects compare with alternatives. It also does not support medical advice. The statistical meaning is bounded by the available outcome reporting, the single-group structure, and the absence of documented methods for estimating and expressing uncertainty.

13. Why This Trial Matters Statistically

This trial is statistically useful as an example of the distinction between an outcome being defined and an outcome being reported. The registry specifies a numeric pain scale, a baseline reference, follow-up through 4 hours, and scheduled assessment times. Yet it does not give numerical primary-outcome results. A clear endpoint definition helps readers understand what was intended to be measured, but it does not establish the observed result or its precision.

The study also illustrates the limits of interpreting change over time without a comparator. Repeated ratings can describe the trajectory observed in a group receiving treatment. In general, however, a trajectory alone cannot separate treatment-associated change from natural change, expectations, other care, or measurement conditions. Randomization and a concurrent comparator are design tools that can improve the basis for a treatment contrast; neither is present in this registry description.

Another statistical lesson is that an enrollment figure and an outcome denominator are not necessarily interchangeable. The record gives enrollment of 37 and reports safety counts with 37 at risk, but does not state how many participants contributed to each pain assessment. Reporting outcome-specific denominators, missingness, estimates, and uncertainty would be important for evaluating the primary endpoint.

Finally, the record distinguishes safety counts from a comparative safety analysis. Counts can communicate what was recorded in the study group, but without details on event definitions and a comparator they cannot characterize relative risk. Taken together, the record makes the study question and design legible while showing why complete outcome reporting and a suitable comparison are essential to statistical interpretation.

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 most important limitation for interpreting efficacy is the absence of numerical primary-outcome results in the registry record. Although the pain scale, baseline reference, and follow-up times are described, the record does not give pain scores, changes, variability, confidence intervals, or test results. Consequently, the magnitude and precision of the primary outcome cannot be evaluated.

The design is single-group, open-label and nonrandomized, with no concurrent comparator. This restricts interpretation of any change over time because changes cannot be attributed uniquely to the intervention. The registry does not report other treatments received during follow-up, so their potential contribution cannot be assessed.

Important operational and analysis details are not reported in the registry record. These include the full eligibility criteria, dosing and administration details, outcome-specific analysis populations, completeness of follow-up, handling of missing ratings, and the statistical methods used for repeated measurements. The record also does not report a statistical analysis plan or a sample-size justification.

Safety reporting is limited to counts. The record lists 0 serious adverse events, 7 other adverse events, and 0 deaths, but does not provide the terms for the other events, timing, severity, relatedness, or collection procedures. These details are needed for a fuller interpretation of the safety observations.

Finally, the record’s completed status does not fill these reporting gaps. Enrollment of 37 describes the study record but cannot be assumed to be the denominator for every efficacy measurement. The available registry information therefore supports a limited design and safety description, not a comprehensive assessment of efficacy, precision, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Efficacy and Safety Trial of Intranasal Ketorolac in Emergency Department Patients for the Treatment of Acute Pain — NCT01471639.
• Registry record last updated 2025-08-15; status last verified 2025-07.
• Results first posted 2017-09-12.
• 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.

18. Record Summary

The registry describes a completed, prospective, open-label, nonrandomized, single-group study of intranasal ketorolac for acute pain in emergency department patients. Enrollment was 37. The primary outcome was change in numeric pain rating from baseline, with assessments through 4 hours. The record lists adverse event/side effects as a secondary outcome.

No numerical primary pain-outcome results, confidence intervals, p-values, or detailed analysis methods are reported in the registry record. The safety entries list 0 serious adverse events, 7 other adverse events, and 0 deaths in the intranasal ketorolac group, with 37 at risk. Further details about the other events are not reported. The single-group design does not provide a concurrent treatment comparison.