Sub-dissociative Ketamine for the Management of Acute Pediatric Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sub-dissociative Ketamine for the Management of Acute Pediatric Pain (NCT01951963), a randomized phase 4 study. The primary outcome is Cumulative Narcotic Consumption.

2. Clinical Question

The trial summary also describes recording pain scores from patients, family members, and research staff through 3 hours. Family members were to be contacted after discharge for evaluation using a post-hospitalization behavior questionnaire. Those descriptions establish additional intended assessments, but results for them are not reported in the registry record. The primary comparison therefore addresses subsequent opioid receipt, not pain scores, behavior after discharge, or total opioid-equivalent dose as a continuous measure.

3. Trial Design

The registry record classifies this as a Phase 4, randomized, parallel-group trial. It lists HealthPartners Institute as the sponsor and describes the condition as pain. The recorded enrollment is 77, and the status is completed. The start is recorded as 2012-12 and primary completion as 2015-06.

Participants were assigned to a ketamine or morphine group. The ketamine arm is described as a single intravenous dose of 0.3 mg/kg, and the morphine arm as a single intravenous dose of 0.05 mg/kg. The trial summary says subsequent pain management would use morphine. This is relevant to interpretation: the comparison is between initial study medications in a treatment context where later morphine could be administered, not a comparison of ongoing ketamine with ongoing morphine.

The registry categorizes masking as quadruple. The brief trial summary describes the study as double blinded. The record does not explain this difference or identify which roles were masked, so the masking procedures cannot be characterized further from the registry record.

The primary outcome was assessed through 3 hours after study medication. The summary also describes pain-score recording over that period and family telephone contacts after emergency-department and hospital discharge for behavioral assessment. The timing of the primary outcome is distinct from those later contacts.

The posted primary outcome counts are based on 31 participants in the ketamine group and 32 in the morphine group. These arm counts do not account for the full recorded enrollment of 77. Reasons for the difference, the analysis population definitions, and participant flow are not reported in the registry record. The record includes three outcome measures, but secondary outcome results are not posted. No registry analysis entries are listed, although a comparative estimate for the primary result is posted.

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: 77 met eligibility criteria and 63 were randomized to one of the two study groups.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The number of subjects in each group who received at least one dose of opioids post study drug.

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 Cumulative Narcotic Consumption, measured over 3 hours post study drug administration.

The primary endpoint is titled Cumulative Narcotic Consumption, but the posted measure is a count of participants, not a summed quantity of narcotic medication. Its unit is participants, and its definition is the number in each group who received at least one opioid after the study drug. The stated observation window is 3 hours after study drug administration.

The outcome description says administered opioids were converted to morphine equivalents in milligrams using standard equianalgesic calculations. It also says pre-study opioid information was collected. However, the primary results presented are counts of participants who received any post-study-drug opioid; they do not report a group total or average of morphine-equivalent doses. Pre-study opioid collection should therefore not be mistaken for a baseline-adjusted result, since adjustment methods are not reported in the registry record.

This endpoint is used to capture whether participants needed additional opioid medication after their assigned initial dose. A binary participant outcome can be compared between groups as the chance of any subsequent opioid receipt, while retaining a straightforward clinical interpretation. It does not describe the amount of opioid used by each participant, the timing or number of later doses, pain relief, or adverse effects. Those questions require distinct outcomes and analyses.

The registry description refers to whether a participant received morphine after study medication, including receipt within one hour or at all. The primary result is reported over the stated 3-hour timeframe. The posted counts are 19 of 31 ketamine participants and 14 of 32 morphine participants. They show the observed number meeting the endpoint in each group; they do not alone establish why medication was given or how participants felt.

7. Results Posted in the Registry

• Morphine: 43.8% (14/32) versus 61.3% (19/31) on control; risk difference -17.5 percentage points (95% CI -41.8 to 6.7), risk ratio 0.71 (0.44–1.16); unadjusted two-proportion z-test p = 0.163.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a binary participant outcome: each participant either received at least one opioid after study medication or did not. This kind of outcome is often summarized as a count in each group and compared using measures of absolute and relative difference. The registry posts a risk difference, relative risk, and odds ratio. The specific statistical test, model, and interval-construction method are not reported in the registry record.

What does the risk difference express?

A risk difference subtracts the event probability in one group from the event probability in the other. Here, the comparison is morphine relative to ketamine, so a negative estimate points toward a lower observed event probability in the morphine group. The confidence interval for the posted risk difference spans zero. Zero is the null value for this measure: it represents equal event probabilities. Because the interval includes zero, the result is compatible with no difference as well as with values on either side of no difference.

How do relative measures differ?

A relative risk compares the event probability in one group with the event probability in the other. A value at its null represents equal probabilities; values on either side indicate a relative increase or decrease. An odds ratio compares event odds rather than event probabilities. For outcomes that are not rare, odds and probabilities are not interchangeable, so the odds ratio should not be read directly as a change in probability. The posted relative-risk and odds-ratio intervals both include their null values. Neither measure removes uncertainty simply because it is expressed on a relative scale.

What does a confidence interval communicate?

A confidence interval describes uncertainty around an estimate under the statistical method used. It is not a range containing a known true value with certainty, and it is not a prediction interval for individual participants. Its width reflects how much precision the data and method support. An interval spanning the null indicates that the data do not sharply distinguish a difference from no difference at the interval’s stated level. The registry record does not identify the confidence level or the exact interval method, so those details should not be assumed.

How should the p-value be read?

The posted unadjusted p-value is 0.163. In general, a p-value is calculated under a null hypothesis and analysis assumptions; it indicates how unusual data at least as incompatible with that null would be under those assumptions. It is not the chance that the groups are equal, nor a direct measure of effect size, precision, or clinical relevance. Since the test and analysis details are not reported, the p-value should be interpreted only as the registry’s posted unadjusted result.

Random allocation is intended to make the groups comparable on average, including with respect to characteristics not used to assign treatment. It does not guarantee that every baseline feature is balanced in a particular trial. Baseline characteristics and adjustment methods are not reported in the registry record, so the posted estimate cannot be described as adjusted for any specific covariates. The record also does not identify an intention-to-treat or per-protocol analysis population.

The outcome is binary, so the reported comparison concerns event occurrence rather than a continuous measure of dose. No over-dispersion parameter is reported or needed to interpret the endpoint as defined. In general, over-dispersion refers to greater variability than a statistical model expects; it can affect uncertainty estimates when the chosen model assumes less variability. Whether any model assumptions were checked or addressed is not reported in the registry record.

Finally, statistical interpretation should distinguish the planned clinical question from the reported data. The summary describes opioid-equivalent calculations and pain and behavior assessments, while the posted primary comparison is a count of participants receiving any post-study-drug opioid. These are different summaries. The latter does not tell how much medication recipients used, and it cannot stand in for the unreported pain or behavioral results.

10. Confidence Intervals and Precision

The point estimate is only one part of the primary result. The risk-difference confidence interval extends across zero, and the relative-risk and odds-ratio intervals extend across their null values. That means the uncertainty includes no difference under each measure. The intervals also extend to values consistent with differences in either direction, so the observed direction should not be treated as precisely established.

The arm counts contributing to the primary result are 31 in the ketamine group and 32 in the morphine group. The event counts are 19 and 14, respectively. The confidence intervals are broad in relation to the range of possible effects, indicating limited precision in the comparative estimate. No exact confidence level or interval method is reported in the registry record, so the intervals’ coverage cannot be described more specifically.

Precision and statistical significance are related but not interchangeable. A wide interval can include the null even when the point estimate is not zero; that does not mean the observed groups had identical results. It means the data do not tightly locate the underlying group difference. Conversely, a small p-value would not by itself show that an estimate is precise or important. The unadjusted p-value is 0.163, and interpretation should consider it alongside the interval and the event counts.

The recorded trial enrollment is 77, while the primary outcome arm counts total 31 and 32 participants. The reasons for the difference and the handling of missing outcome data are not reported in the registry record. If participants with unavailable outcomes were excluded, the degree to which their exclusion could affect the estimate cannot be assessed from the posted details. The absence of this information limits evaluation of precision as well as potential bias.

11. 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 calculations. They are participants per arm, not total events. The assumptions stated for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration considers detecting the stated fraction of the observed effect. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

For planning based on 100% of the observed effect, the figures are 127 participants per arm for 80% power and 169 participants per arm for 90% power. For planning based on 75% of the observed effect, the corresponding figures are 224 participants per arm for 80% power and 299 participants per arm for 90% power. For planning based on 50% of the observed effect, they are 500 participants per arm for 80% power and 668 participants per arm for 90% power.

In plain terms, the 80% column gives the estimated number per arm for a study designed to have an 80% chance of detecting the assumed effect if that effect is real and the planning assumptions hold. The 90% column expresses the same kind of planning target with a higher desired chance of detection. These are not observed power for the completed trial; they are illustrations for future planning under the stated assumptions.

The assumed effect gets smaller across the planning scenarios, and the required participant count rises. Smaller effects are harder to distinguish from random variation, so planning to detect them generally requires more participants. The values depend on the observed effect used as their reference; they should not be mistaken for a sample-size recommendation based on an independently justified clinical effect.

12. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.613; treatment proportion p₁ = 0.438; average p̄ = 0.525.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7062 = 1.3841.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6952 = 0.5851.
4. n = (1.3841 + 0.5851)² / (-0.1754)² = 126.0, rounded up to 127 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
p0 <- 0.612903225806452                          # control proportion
p1 <- 0.4375                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1951963)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 127 (80% power), 169 (90% power)
 75% of observed effect: n per arm = 224 (80% power), 299 (90% power)
 50% of observed effect: n per arm = 500 (80% power), 668 (90% power)
power.prop.test: 126 
Simulated power at n = 127 per arm: 0.805 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, but secondary outcome results are not posted. It does not report whether the trial had a prespecified hierarchy of outcomes, whether analyses were planned for multiple time points or subgroups, or whether multiplicity adjustments were intended. The primary result therefore cannot be evaluated in the context of a documented multiplicity strategy. When several hypotheses are tested, the chance of at least one apparently unusual result can increase; methods such as prespecification, hierarchical testing, or adjustment can address that issue, but their use in this trial is not reported.

The registry record gives an unadjusted p-value of 0.163 for the posted comparison. No adjusted p-value or multiplicity procedure is reported. The existence of a single posted comparison does not establish that only one analysis was conducted, particularly because the trial summary describes other measurements. The number and outcomes of any unreported or unpublished analyses are not reported in the registry record.

Missing-data handling is also not described. The primary outcome has arm counts of 31 for ketamine and 32 for morphine, while recorded enrollment is 77. The record does not explain the participant flow, whether every randomized participant had an outcome recorded, or how any unavailable outcomes were handled. It also does not report reasons for withdrawal or exclusion. Without these details, the potential effects of missing outcomes on the comparison cannot be assessed.

The analysis population is not defined in the registry record. It is not stated whether the primary analysis followed intention-to-treat, per-protocol, or another population definition. Baseline comparability, covariate adjustment, protocol deviations, and sensitivity analyses are likewise not reported. These omissions do not change the posted counts, but they limit assessment of how closely the analysis matches the randomized comparison and how robust the result may be to alternative analytic choices.

14. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 31 participants at risk in the ketamine group and 32 at risk in the morphine group, with 0 serious adverse events affecting participants in either group. No serious adverse event terms are listed. These figures describe the serious events recorded in the registry; they do not establish that no serious event could occur outside the recorded observation or reporting process.

For other adverse events, the record lists 2 affected participants among 31 at risk in the ketamine group and 2 among 32 at risk in the morphine group. These are participant counts, not event rates calculated here, and no event descriptions are included in the posted details. The registry does not report the severity, timing, or relationship assessments for these other events.

Death counts are not reported in the registry record. The serious-event counts should be interpreted alongside the size of the groups and the limited safety detail available. They do not support a broad comparison of safety, and the posted primary efficacy outcome does not answer a safety question.

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

The result documents a difference in observed counts: 19 of 31 participants in the ketamine group and 14 of 32 in the morphine group received at least one opioid after the study medication. The posted comparison is oriented as morphine relative to ketamine, and its point estimate is negative. This is a description of the primary outcome among the participants represented in the posted result, not proof of a causal explanation for every subsequent opioid decision.

The uncertainty matters. The risk-difference interval includes zero, and the relative-risk and odds-ratio intervals include their null values. The unadjusted p-value is 0.163. Together, these results do not establish a clear difference in the endpoint, while the interval estimates do not rule out differences in either direction. They also do not establish equality between the groups.

The endpoint is limited to whether a participant received any opioid after study medication during the stated timeframe. It does not report the total morphine-equivalent dose, pain-score change, duration of pain, satisfaction, or later behavior. The trial summary describes some of those assessments as planned, but their results are not reported in the registry record. No conclusion about them should be drawn from the primary endpoint.

The treatment comparison also concerns a single assigned initial dose within a care plan where subsequent pain management was described as morphine. It is not a comparison of prolonged ketamine treatment with prolonged morphine treatment. The record does not report details needed to assess all aspects of implementation, participant flow, or missing outcome handling.

These results are best read as an imprecise randomized comparison of post-study-drug opioid receipt in this trial. They neither establish a treatment benefit nor demonstrate an absence of benefit or harm. The posted counts and uncertainty describe the evidence available for this endpoint; they do not replace the unreported results for other measures or a broader assessment of clinical outcomes.

16. Why This Trial Matters Statistically

This trial illustrates how an endpoint’s label can differ from the quantity actually analyzed. Although the primary measure is titled Cumulative Narcotic Consumption and the description mentions morphine-equivalent calculations, the posted result counts participants who received any opioid after study medication. That distinction is statistically important: a binary event count answers whether additional opioid was received, whereas a dose total would address how much was administered.

The comparison also illustrates why point estimates should be read with their uncertainty. The observed event counts differ, and the point estimate is negative for the morphine-relative-to-ketamine contrast. Yet the confidence intervals include the null values, and the unadjusted p-value is 0.163. A reader should not reduce the evidence to either the direction of the point estimate or a single significance threshold. The interval and the endpoint definition shape what can be concluded.

Another important issue is the distance between trial enrollment and the arm counts contributing to the primary result. Enrollment is recorded as 77, while the outcome counts are based on 31 and 32 participants. Because the record does not explain this difference or specify the analysis population, readers cannot fully assess participant flow or missing-outcome risk. This is a reminder that transparent accounting of randomized participants and outcome availability is essential to interpreting randomized comparisons.

The record also demonstrates the limits of registry results when secondary outcomes and analysis details are absent. Pain scores and later behavioral assessments are described in the trial summary, but their results are not posted. The primary result therefore cannot serve as a proxy for those outcomes, and the lack of a documented multiplicity or missing-data plan constrains statistical appraisal.

17. 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 follow from the information in the registry record. First, recorded enrollment is 77, while the primary outcome arms contain 31 and 32 participants. The record does not provide a flow diagram, reasons for exclusions or missing outcomes, or an analysis-population definition. This prevents a complete account of how the randomized participants relate to the primary comparison.

Second, the outcome title suggests cumulative consumption, but the posted result is a count of participants receiving at least one post-study-drug opioid. Dose totals, distributions of morphine-equivalent use, and the number or timing of subsequent doses are not reported. This narrows the endpoint’s interpretation to whether any additional opioid was received.

Third, the comparative intervals include their null values, and the unadjusted p-value is 0.163. The result is therefore imprecise, and the registry does not report the interval confidence level, test, or interval method. A full independent assessment of the analysis cannot be made from the available statistical details.

Fourth, although the summary describes pain scores and behavioral follow-up, results for these assessments are not reported in the registry record. Secondary outcome results are not posted, and no multiplicity approach is described. Safety information is also limited: serious adverse events are reported as zero in both groups, other adverse events as two in each group, and death counts are not reported. Event descriptions and additional safety details are unavailable.

Finally, the record’s masking classification and its brief-summary description use different labels, and the discrepancy is not explained. These gaps limit assessment of masking procedures, participant flow, analysis choices, and the broader clinical context of the primary result.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Sub-dissociative Ketamine for the Management of Acute Pediatric Pain — NCT01951963.
• Registry record last updated 2018-07-03; status last verified 2018-06.
• Results first posted 2017-10-16.
• 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.

21. Record Summary

The registry record describes a completed Phase 4 randomized, parallel-group trial sponsored by HealthPartners Institute. The recorded enrollment is 77. Participants were assigned to a single intravenous ketamine dose of 0.3 mg/kg or a single intravenous morphine dose of 0.05 mg/kg.

The primary endpoint counts participants receiving at least one opioid after study medication through 3 hours. The posted counts are 19 of 31 in the ketamine group and 14 of 32 in the morphine group. The unadjusted p-value is 0.163, and the confidence intervals for the posted comparison measures include their null values.

The registry describes planned pain-score and post-discharge behavioral assessments, but secondary results are not posted. Participant flow, missing-data handling, analysis populations, and details of the statistical plan are not reported in the registry record. Serious adverse events are recorded as 0 in both groups; other adverse events affect 2 participants in each group. Death counts are not reported.