Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine (IN) for Postoperative Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine (IN) for Postoperative Pain (NCT01351090), a randomized phase 2 study. The primary outcome is Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours.

2. Clinical Question

The study’s primary objective was to evaluate analgesic efficacy across multiple intranasal ketorolac doses over 2 days. Its primary outcome was total morphine sulfate use in milligrams through 24 hours, recorded in 8-hour intervals from the start of dosing. This outcome concerns rescue medication use, not a direct measure of pain intensity.

The registry reports mean morphine use of 54.32 mg for the 10 mg group, 37.77 mg for the 30 mg group, and 56.45 mg for placebo. The posted unadjusted recalculation compares each active group with placebo. The estimated difference for 10 mg is -2.13 mg, with a confidence interval that includes zero; for 30 mg it is -18.68 mg, with a confidence interval from -20.8 to -16.56 mg. These are descriptive comparisons of the posted summaries, not a substitute for a sponsor-reported analysis, which is not reported in the registry record.

The clinical question is therefore narrow: how the reported rescue-morphine totals differed across the randomized groups during the specified period. It does not by itself establish how participants’ pain changed, explain why morphine use differed, or answer broader questions about safety or outcomes beyond the registry’s listed measures.

3. Trial Design

The registry describes a completed, Phase 2, randomized, double-blind, parallel-group study of intranasal ketorolac for postoperative pain. Participants who had undergone major surgery were assigned to intranasal ketorolac 10 mg, intranasal ketorolac 30 mg, or placebo vehicle. The registry reports enrollment of 127. Its brief summary describes screening, a 2-day treatment period, and a follow-up visit.

Study dosing began after surgery when a participant’s pain intensity rating reached at least 40 on a 100-mm visual analog scale. Study drug was then administered every 8 hours, with the last dose given at 40 hours. Participants could use morphine sulfate through patient-controlled analgesia if study drug did not relieve pain. The protocol details beyond this summary, including any further rules for treatment or rescue medication, are not reported in the registry record.

The primary objective was to evaluate analgesic efficacy across multiple doses over 2 days. Safety and tolerability were secondary objectives. The primary outcome focused on total morphine sulfate use through 24 hours; the posted secondary outcomes include morphine use over longer intervals and pain intensity difference scores. Results are posted for the primary outcome and three secondary measures.

For the primary outcome, the reported group sizes are 41 for each treatment group. These are outcome-specific counts and should not be treated as a complete account of enrollment or of the analysis population. Safety results use different at-risk counts. The registry record does not explain the differences among these denominators. Details of the randomization sequence, allocation concealment, blinding procedures, protocol deviations, and analysis populations are 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: Subjects must have been requesting pain medication and have at lease moderate pain defined as a score of at least 40 mm on a 100-mm VAS.

Overall Study

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 Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours, measured over 8-hour intervals from the start of dosing through 24 hours.

The primary endpoint is total morphine sulfate use, in milligrams, through 24 hours after dosing began. It is reported as a mean with a standard deviation, with measurements described in 8-hour intervals from the start of dosing through 24 hours. The registry provides a group mean for each randomized arm.

This measure captures use of rescue analgesia available through patient-controlled analgesia. It is relevant to the study’s analgesic-efficacy objective because participants could use morphine when study drug did not relieve pain. Lower reported morphine use indicates less morphine was recorded for that group over the specified interval; it does not, by itself, establish the reason for that use or provide a complete measure of pain experience.

General statistical context: a continuous outcome such as total drug use can be summarized by its mean, which describes the group’s average, and standard deviation, which describes variability among observations. Comparing group means provides an estimate of the average difference, while a confidence interval conveys uncertainty around that estimate. Neither summary describes every participant’s outcome.

The endpoint is not a direct pain-intensity score. Pain intensity difference is listed separately among the secondary outcomes, at a different assessment time. The registry record does not report further details about endpoint construction, handling of missing measurements, or the sponsor’s statistical model for the primary comparison.

7. Results Posted in the Registry

• Ketorolac IN 10 mg: mean 54.32 versus 56.45 on control; difference -2.13 (95% CI -4.57 to 0.31), standardized effect d = -0.38; z-test p = 0.087.
• Ketorolac IN 30 mg: mean 37.77 versus 56.45 on control; difference -18.68 (95% CI -20.80 to -16.56), standardized effect d = -3.81; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ketorolac IN 10 mg: mean 78.66 versus 87.87 on control; difference -9.21 (95% CI -13.83 to -4.59), standardized effect d = -0.89; z-test p = <0.001.
  • Ketorolac IN 30 mg: mean 61.39 versus 87.87 on control; difference -26.48 (95% CI -31.11 to -21.85), standardized effect d = -2.63; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ketorolac IN 10 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ketorolac IN 30 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ketorolac IN 10 mg: mean 28.25 versus 32.61 on control; difference -4.36 (95% CI -6.70 to -2.02), standardized effect d = -0.83; z-test p = <0.001.
  • Ketorolac IN 30 mg: mean 23.11 versus 32.61 on control; difference -9.50 (95% CI -11.81 to -7.19), standardized effect d = -1.89; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ketorolac IN 10 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ketorolac IN 30 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Pain Intensity Difference (PID) Scores

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ketorolac IN 10 mg: mean 34.10 versus 29.10 on control; difference 5.00 (95% CI 3.93 to 6.07), standardized effect d = 1.99; z-test p = <0.001.
  • Ketorolac IN 30 mg: mean 38.90 versus 29.10 on control; difference 9.80 (95% CI 8.86 to 10.74), standardized effect d = 4.45; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Ketorolac IN 10 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Ketorolac IN 30 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the posted secondary outcomes, both ketorolac groups have lower mean morphine use than placebo for the longer reported intervals, while pain intensity difference scores are higher in both ketorolac groups. Thus, the general direction across these different measures is consistent with the primary comparison’s pattern of lower reported rescue-morphine use in the active groups. The outcomes do not measure exactly the same thing: morphine use records rescue-medication consumption over time, whereas pain intensity difference scores describe a pain measure at a specified assessment.

The secondary results add context but should not be treated as independent confirmation of the primary result. The outcomes share participants and study procedures, and their measures may be related. The registry record lists three secondary outcomes but does not report a multiplicity plan or sponsor analyses. Unadjusted comparisons can make a collection of findings appear more conclusive than it is when many outcomes or group comparisons are considered together.

The posted recalculations for the secondary comparisons are unadjusted and based on the group summaries. Their p-values are <0.001 for the listed comparisons. Those values do not account for any adjustment across outcomes or comparisons. The registry record does not report whether the sponsor specified a hierarchy, selected a subset for confirmatory inference, or controlled the overall false-positive risk.

For these reasons, the secondary measures are best read as complementary descriptive evidence about rescue-morphine use and pain ratings in the trial, rather than as a basis for claims beyond the primary endpoint. They cannot resolve missing details about the analysis plan or missing data. Nor do they establish that the primary and secondary measures capture the same clinical experience. Their value is in showing whether the broad observed pattern is similar across different recorded outcomes, while retaining appropriate caution about unadjusted comparisons.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours
• Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours
• Pain Intensity Difference (PID) Scores

9. Statistical Interpretation

10. Statistical Methods Explained

General statistical context: the primary outcome is continuous, so the posted summaries use a mean and standard deviation for each group. The mean represents the group average in milligrams of morphine sulfate, while the standard deviation describes the spread of individual observations around that average. The standard deviation is not the uncertainty in the mean difference; uncertainty in a comparison also depends on the number of observations and the variability in the groups.

What does a mean difference describe?

The unadjusted mean difference compares each ketorolac group’s mean with the placebo mean. In these calculations, the active-group mean is subtracted from the placebo-group mean in the order active minus placebo. A negative estimate means the active group’s posted mean was lower. For the primary outcome, the registry means yield estimates of -2.13 mg for 10 mg and -18.68 mg for 30 mg. These estimates are descriptive comparisons of group averages; they do not characterize how much individual participants’ outcomes overlapped.

The posted comparisons are labeled as recalculated and are based on the summary statistics, rather than on a reported adjusted model. The registry record lists no reported analyses for the primary outcome. It does not specify whether the original analysis used covariate adjustment, how repeated measurements were handled, or which analysis population was intended. These details matter because an adjusted model or a different analysis population can produce estimates and uncertainty that differ from a calculation based only on the posted means and standard deviations.

What does a confidence interval add?

General statistical context: a confidence interval gives a range of values compatible with the data and the calculation’s assumptions. It conveys the estimate’s precision; a narrower interval indicates less uncertainty around the estimated difference than a wider interval. It is not a range containing a known proportion of individual participants’ outcomes, and it does not guarantee that the true effect lies inside the interval.

The interval for the 10 mg comparison includes zero, while the interval for the 30 mg comparison lies below zero. Zero represents no difference between group means. The first interval therefore does not separate the estimated comparison from zero at the interval’s stated level; the second does. The registry record does not identify the confidence level or method used for a sponsor analysis, because it does not report one. The intervals discussed are those from the unadjusted recalculation.

How should p-values be read?

General statistical context: a p-value describes how unusual results at least as inconsistent with a null hypothesis of no difference would be under the statistical assumptions used for the calculation. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The unadjusted p-values for the primary comparisons are 0.087 for 10 mg and <0.001 for 30 mg. They do not account for any multiplicity adjustment, and the record does not report whether the sponsor conducted one.

A small p-value does not resolve limitations in the underlying analysis, missingness, measurement, or generalizability. Conversely, a p-value above a conventional threshold does not prove that groups are equivalent. Interpretation should consider the estimated difference and its interval, the endpoint’s meaning, and the completeness of the registry’s analysis reporting.

Why does variability matter?

General statistical context: larger variability makes a group mean less precise when other features are held constant. The standard deviations posted for the primary outcome are 6.36 mg for 10 mg, 4.98 mg for 30 mg, and 4.82 mg for placebo. The recalculated comparisons use the group sizes and standard deviations available in the record. The registry record does not report how the original study analysis handled the distribution of morphine use or whether it used a model suited to any particular distributional feature.

Randomization and double blinding are design features intended to reduce certain forms of bias. They do not remove every source of uncertainty, and they do not replace transparent reporting of the analysis plan, outcome data, and missing-data handling. The registry record does not report those details. The available results support a reading of the posted summaries and recalculations, not a reconstruction of every part of the trial’s statistical analysis.

11. Confidence Intervals and Precision

The primary comparison for intranasal ketorolac 10 mg has a recalculated mean difference of -2.13 mg, with a confidence interval from -4.573 to 0.313 mg. The interval includes zero and also includes values on either side of zero. This means the estimated difference is imprecise with respect to whether the mean difference is below or above zero. The unadjusted p-value is 0.087.

For intranasal ketorolac 30 mg, the recalculated mean difference is -18.68 mg, with a confidence interval from -20.8 to -16.56 mg. This interval is entirely below zero. Its location indicates that the posted summaries estimate lower mean morphine use in the 30 mg group than in the placebo group, and the interval does not include zero under this recalculation. The unadjusted p-value is <0.001.

General statistical context: precision is about uncertainty in an estimate, not whether an estimate is clinically important or whether a result should determine care. A confidence interval’s width reflects the information and assumptions used in its calculation. Here, these intervals come from simple unadjusted recalculations from posted summary statistics. They are not a substitute for a sponsor-reported interval or analysis, which is not reported in the registry record.

The posted means and standard deviations give useful information about group-level averages and variability, but the record does not provide individual-level distributions, an account of missing measurements, or detailed analysis methods. Those omissions limit assessment of how robust the estimates are to the study’s analysis choices. The intervals should be interpreted alongside these reporting limits, rather than as complete descriptions of uncertainty about the study or its broader implications.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. They give participants per arm for 80% power and participants per arm for 90% power. They do not give total participants across groups or total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms being compared, and a normal approximation. For each scenario, the effect to detect is the stated fraction of the observed effect.

In plain terms, the 80% power column describes the estimated participants per arm for a future two-arm study to have an 80% chance of detecting the stated effect under those assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning figure for a higher target chance of detection. These are prospective design calculations, not an estimate of how likely the completed trial was to detect an effect.

The rows use the full observed effect and smaller fractions of it. Planning for a smaller effect requires more participants per arm, because smaller differences are harder to distinguish from random variation under the same assumptions. The figures are sensitive to the observed effect used as their starting point, so unusually large observed differences can produce very small illustrative sample-size estimates. Such estimates should not be interpreted as evidence that a future study could reliably achieve the same result.

These figures are not observed power. The registry record does not report the assumptions used for the trial’s own original design or its sample-size justification. The planning illustration is separate from those unreported original design details.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.130; pooled standard deviation σ = 5.643.
2. n = 2 × (1.96 + 0.842)² × 5.643² / -2.130² = 110.2, rounded up to 111 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.13                      # observed difference in means
sigma <- 5.64278300132124                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1351090)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 111 (80% power), 148 (90% power)
 75% of observed effect: n per arm = 196 (80% power), 263 (90% power)
 50% of observed effect: n per arm = 441 (80% power), 590 (90% power)
power.t.test: 111.1 
Simulated power at n = 111 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and three secondary outcomes, with comparisons of each ketorolac group against placebo. It does not report a multiplicity strategy, such as whether a particular outcome order or adjustment was prespecified. When several comparisons are examined, the chance of observing at least one apparently unusual result can increase. General statistical context: multiplicity procedures address this issue by changing how evidence is assessed across a family of tests. Without a reported strategy, the unadjusted p-values should not be read as controlling error across all outcomes and comparisons.

The registry record reports no analyses for the outcomes. As a result, the recalculated estimates and p-values are not sponsor-reported inferential results. The record does not state whether the posted endpoints were analyzed according to an intention-to-treat, per-protocol, or other population definition. It also does not report prespecified covariates, model form, analysis of repeated measurements, or procedures for deviations from the assigned treatment.

Missing-data information is not reported in the registry record. The outcome-specific reported group sizes differ across measures, and the record does not explain why. These values should be read as the counts posted for each outcome, not as proof of the reason any measurement is absent. Without information about missingness, imputation, or sensitivity analyses, it is not possible to assess whether incomplete outcome data could have affected the reported group summaries.

General statistical context: randomization supports comparison of groups as assigned, but missing outcome data can weaken that protection if the availability of measurements is related to outcomes or treatment. Transparent reporting of analysis populations and missing-data methods helps readers judge this risk. Those details are not reported in the registry record. These gaps do not establish that a particular bias occurred; they limit how fully the posted comparisons can be evaluated.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (4.8%), peritonitis (2.4%), thrombus in popliteal vein (2.4%), myocardial infarction (2.4%), allergic reaction (2.4%).

The registry reports serious adverse events among participants at risk in each group. The number reported as affected is 3 in the ketorolac 10 mg group, 5 in the ketorolac 30 mg group, and 1 in the placebo group. The corresponding at-risk counts are 43, 42, and 42. These are safety figures and should not be substituted for the outcome-specific counts reported for efficacy measures.

Serious-event terms listed in the record include pulmonary embolism at 4.8%, peritonitis at 2.4%, thrombus in popliteal vein at 2.4%, myocardial infarction at 2.4%, allergic reaction at 2.4%, and vaginal hemorrhage at 2.3%. The record does not assign these listed terms to treatment groups in the information, so they should not be attributed to a particular arm.

These figures describe events recorded in this trial; they do not by themselves establish whether an event was caused by study treatment or permit a complete comparison of safety. Deaths are not reported in the registry record. The registry’s further safety-analysis methods and details about event ascertainment are also not reported.

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

The posted results describe group averages in a randomized, double-blind study of intranasal ketorolac and placebo after major surgery. For the primary outcome, the 10 mg group’s recalculated mean difference from placebo is close to zero and its interval includes zero. The 30 mg group’s recalculated mean morphine use is lower than placebo, with an interval below zero. These statements describe the posted outcome summaries and the uncertainty in the simple unadjusted comparisons.

They do not establish that a treatment works or does not work. The registry record does not report sponsor analyses, analysis populations, missing-data procedures, or a plan for handling multiple comparisons. The recalculated estimates therefore cannot answer every question that a prespecified, fully reported analysis might address. Unadjusted p-values should not be taken as controlling false-positive risk across the primary and secondary comparisons.

The primary measure is morphine sulfate use through 24 hours, not a direct measurement of pain intensity. Differences in rescue-morphine use may be related to pain, but the group summaries do not reveal why participants used different amounts. Pain intensity difference scores appear as a separate secondary measure, and neither outcome alone captures all aspects of postoperative pain or recovery.

The findings also concern the enrolled study population and the specified observation periods. They do not establish what would occur in other populations, under different dosing or rescue procedures, or over time beyond the registry’s reported measures. Safety counts likewise describe events recorded in the trial but do not establish causation or provide a complete account of comparative safety.

A careful reading separates the descriptive pattern from what remains uncertain: the group means, estimated differences, and intervals are reported; the analysis details needed to fully judge inferential strength and missing data are not reported in the registry record.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical outcome’s meaning matters as much as its numerical comparison. The primary endpoint is total rescue-morphine use, which can be summarized as a continuous measure and compared by group means. It is relevant to the study objective, but it is not interchangeable with a pain-intensity measure. Interpreting the endpoint requires keeping the rescue-treatment context in view.

It also shows the value of reporting both estimates and uncertainty. The 10 mg comparison has an interval that includes zero, while the 30 mg comparison’s interval lies below zero. Those intervals communicate different levels of precision and different compatibility with no mean difference. A p-value alone would not convey the size or range of the estimated comparison.

The registry record also demonstrates why recalculations should be distinguished from sponsor analyses. Group summaries can support transparent, simple comparisons, but they do not reveal the full analysis plan, analysis population, missing-data handling, or multiplicity approach. Where those details are absent, interpretation should remain proportionate to the information actually reported.

Finally, the sample-size illustrations are useful for understanding how planning depends on the effect one aims to detect. Their figures use the observed effects and stated assumptions; they do not reconstruct the trial’s original design or show observed power. This distinction helps avoid treating an illustration based on the completed trial’s results as independent evidence about the trial’s success.

18. 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 follow from the registry record. Although the study is described as randomized and double-blind, details of sequence generation, concealment, and implementation of blinding are not reported. The record also does not describe how protocol deviations were handled or define the analysis population for the posted outcomes.

The primary and secondary group counts are outcome-specific, and their differences from the safety at-risk counts are not explained. The registry record does not report the amount or pattern of missing data, the reasons for missing measurements, or any imputation or sensitivity analyses. Consequently, the available summaries do not show whether incomplete data could have influenced the comparisons.

The registry record lists no reported analyses for the outcomes. The displayed comparisons are unadjusted recalculations from group means, standard deviations, and counts. No sponsor-reported model, adjustment, or multiplicity strategy is reported. This limits evaluation of whether the recalculations align with the intended analysis or how the collection of primary and secondary results was interpreted in the original analysis.

The main endpoint measures rescue-morphine use rather than pain intensity, and access to morphine through patient-controlled analgesia is part of the study context. The posted summaries cannot explain the factors underlying group differences in use. The registry record also does not report further detail about endpoint distribution or the handling of repeated observations. These limits do not show that the results are biased; they identify uncertainties that the reported information cannot resolve.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine (IN) for Postoperative Pain — NCT01351090.
• Registry record last updated 2012-10-18; status last verified 2012-09.
• Results first posted 2012-10-18.
• 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.

22. Record Summary

The registry describes a completed, Phase 2, randomized, double-blind, parallel-group study of intranasal ketorolac 10 mg, intranasal ketorolac 30 mg, or placebo vehicle for postoperative pain after major surgery. Enrollment is reported as 127. Treatment lasted 2 days, with dosing every 8 hours after pain reached the specified threshold and access to morphine sulfate through patient-controlled analgesia for pain not relieved by study drug.

The primary outcome was total morphine sulfate use through 24 hours. Posted means were 54.32 mg for 10 mg ketorolac, 37.77 mg for 30 mg ketorolac, and 56.45 mg for placebo. Unadjusted recalculations show a mean difference of -2.13 mg for 10 mg and -18.68 mg for 30 mg. The 10 mg comparison’s confidence interval includes zero; the 30 mg comparison’s interval lies below zero.

Three secondary outcomes and serious adverse event counts are also reported. Sponsor analyses, multiplicity procedures, analysis populations, and missing-data methods are not reported in the registry record, so the recalculated comparisons should be interpreted as unadjusted summaries rather than a complete account of the trial’s planned analysis.