Geriatric Ketamine for Pain Management Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Geriatric Ketamine for Pain Management Study (NCT02673372), a randomized phase 4 study. The primary outcome is Reduction of Pain Score at 30 Minutes.

2. Clinical Question

The clinical question is framed as a comparison of two treatments in an emergency department setting, not as a comparison with no treatment. The registry's stated motivation is to reduce opioid administration in older patients because of concerns about possible side effects. That motivation explains the research context, but it does not establish what the trial found about side effects or comparative effects on pain.

The primary outcome is described as comparative reduction in pain scores between the groups at 30 minutes. The record reports group means and standard deviations for this outcome, along with a between-group mean difference and confidence interval. It does not report the population details needed to determine which participants contributed to the outcome analysis, or whether all enrolled participants had outcome data at that time.

3. Trial Design

This is a Phase 4, randomized, parallel-group study with quadruple masking, according to the registry record. It is titled the Geriatric Ketamine for Pain Management Study, and its official title describes a prospective, randomized, double-blind comparison of low-dose ketamine and morphine for moderate to severe pain in the emergency department geriatric population. The record lists enrollment of 60 participants.

The study compared two active drug groups. The morphine group received 0.1 mg/kg intravenously by infusion over 10 minutes, with a maximum dose of 10 mg. The ketamine group received 0.3 mg/kg intravenously by infusion over 10 minutes, described as a sub-dissociative dose. Each group has posted outcome data for 30 participants. The registry reports no confidence limits around the individual group means.

The record lists the study as completed. Its recorded start is 2016-04 and its primary completion is 2018-02. Those dates describe the registry timeline; they do not provide details about when individual participants were enrolled or followed.

Random allocation means that assignment to the study groups was intended to be determined by chance. Masking is intended to limit the influence of knowledge of assignment on aspects of trial conduct or assessment. The registry identifies the masking as quadruple, but does not specify which roles were masked or describe how masking was maintained. The record also does not report the randomization procedure, allocation concealment, or the original protocol's sample-size justification.

The posted record includes one primary outcome measure and no posted secondary outcome measures. It reports no analyses in the analysis-count field. This does not establish that no additional analyses were conducted; it means that such analysis details 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.

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 Reduction of Pain Score at 30 Minutes, measured over 30 minutes.

The primary endpoint is titled Reduction of Pain Score at 30 Minutes. It concerns the comparative reduction in NRS pain scores between the ketamine and morphine groups 30 minutes after medication administration. The NRS is a numerical rating scale described in the record as ranging from 0 to 10, where 0 means no pain, 10 means very severe pain, and 5 is moderate pain.

Pain scores are continuous measurements for the purpose of the reported analysis. A mean summarizes the average observed score or reduction in a group, while a standard deviation describes how spread out individual observations are around that mean. The registry reports means and standard deviations for the two groups and a mean difference between them.

A measurement at a defined time point makes a comparison between groups possible at that point in the treatment period. A short-term endpoint may describe the recorded pain response at that assessment, but it does not by itself describe later pain, duration of relief, or other outcomes. The record does not report secondary outcome measures, so the posted primary outcome should not be treated as a complete account of every possible benefit or harm assessed during the study.

The registry's description identifies the outcome as reduction from baseline, but the record does not separately report the baseline group summaries or detail how any change score was calculated. The posted group values are therefore best read as the registry's reported primary-outcome summaries, rather than as a basis for reconstructing individual participants' changes.

7. Results Posted in the Registry

• Ketamine Group: mean 4.20 versus 4.40 on control; difference -0.20 (95% CI -1.85 to 1.45), standardized effect d = -0.06; z-test p = 0.812.

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods describe how trial observations are reduced to estimates and how uncertainty in those estimates is assessed. The registry record provides group means, standard deviations, a mean difference, a confidence interval, and an unadjusted p-value for the primary outcome. It does not report a detailed statistical analysis plan, the original sample-size justification, or the method used for the primary analysis. The explanations below describe general concepts and how they relate to the reported summaries; they do not imply that a particular unreported method was used.

What does a mean summarize?

For a continuous outcome, the mean is the arithmetic average of the observed values in a group. Here, the posted means are 4.4 for morphine and 4.2 for ketamine. A mean is a concise description of the group's average result, but it does not show the full distribution of individual observations. Participants can have values well above or below the group mean.

The standard deviation describes dispersion among observations in a group. The registry reports standard deviations of 3.1 for morphine and 3.4 for ketamine. A larger standard deviation indicates more spread around the mean, not greater uncertainty in the mean by itself. Uncertainty in a group mean or in a difference between means also depends on the amount of information available, including the number of observations and their variability.

How should the mean difference be read?

A mean difference expresses the contrast between two group means on the original outcome scale. The posted contrast is for ketamine compared with morphine and is -0.2. Its sign follows the order of subtraction used in the record: the ketamine group mean minus the morphine group mean. The estimate is not a percentage and does not represent a relative risk.

For a continuous measurement, a difference of zero corresponds to equal group means. A negative value indicates a lower mean in the first named group under that comparison order, while a positive value indicates a higher mean. Because the registry describes the endpoint as a reduction, the direction should be read in relation to that endpoint definition; it should not be silently reinterpreted as a raw pain score at follow-up. The record does not provide baseline summaries or a detailed calculation description that would allow a separate reconstruction of the outcome.

What information does a confidence interval add?

A confidence interval gives a range of values that are compatible with the observed estimate under the method and assumptions used to construct it. The reported interval for the mean difference runs from -1.846 to 1.446. Its inclusion of zero means that equality of group means is among the values compatible with the interval. Values in either direction are also included, so the estimate does not pin down the direction of a difference with precision.

In general, a confidence interval is not a guarantee that the true effect lies inside that particular interval, and it is not a probability statement about the effect after the data have been observed. Its practical value is that it displays the range of estimates that remain reasonably compatible with the data and analysis. The confidence level and exact construction method are not stated in the registry record; the interval should therefore be interpreted as posted, without attributing an unreported method to it.

What does the p-value say?

The unadjusted p-value is 0.812. In general, a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. A large p-value does not prove that the groups are identical. It indicates that the posted result is not statistically incompatible with the null hypothesis under the test used.

The registry labels the result unadjusted. It does not report a multiplicity procedure or say whether this was the only analysis considered in the full study. The record lists one primary outcome and no posted secondary outcomes, but that information is not enough to reconstruct all analyses that may have been planned or performed.

Why can variability matter?

General: When an outcome varies substantially among participants, the group means are harder to estimate precisely unless there is enough information to offset that variability. This is one reason the standard deviations matter when interpreting the mean difference and its confidence interval. The group sizes are 30 in each arm, and the reported standard deviations are 3.1 and 3.4. These summaries help characterize the observed data but cannot reveal individual observations, outliers, or distribution shape.

General: Over-dispersion means that data vary more than a chosen statistical model expects. If present, it can make standard errors too small and confidence intervals too narrow when the model does not account for it. The outcome is reported as a continuous measure with means and standard deviations; the registry record does not report a finding of over-dispersion or a diagnostic assessment. This concept is relevant generally, but should not be presented as a detected problem in this trial.

What can be inferred from the reported analysis?

The posted summary supports a descriptive comparison of the two group means and an inferential summary in the form of a confidence interval and unadjusted p-value. It does not document whether the analysis followed intention-to-treat principles, how missing observations were handled, whether the analysis adjusted for baseline pain, or whether assumptions were checked. These details are not reported in the registry record.

The planning figures associated with the observed effect are illustrations under stated assumptions, not a retrospective assessment of the trial's ability to detect an effect. They should not be confused with the original trial design or with observed power. The record does not report the original design assumptions or sample-size calculation.

10. Confidence Intervals and Precision

The reported mean difference for ketamine compared with morphine is -0.2, with a confidence interval from -1.846 to 1.446. The interval is wide relative to the point estimate and extends across zero. It therefore includes the possibility of a lower mean in the ketamine group, no difference in means, and a higher mean in the ketamine group under the reported comparison order.

Precision concerns how narrowly the data estimate the size and direction of an effect. A point estimate alone can create a misleading impression of certainty; the interval shows that a range of mean differences remains compatible with the result. The interval does not establish that all values within it are equally plausible, nor does it assign a probability to any particular value.

In general, intervals tend to be narrower when estimates are based on more information and less variable observations, subject to the analysis method. In this trial, each group has 30 participants, and the standard deviations are 3.1 for morphine and 3.4 for ketamine. Those summaries give context for the uncertainty but do not identify its source in full. The registry record does not describe interval construction, missing-data handling, or any adjustment used in the analysis.

The interval should not be treated as proof of equivalence. Such a conclusion requires a prespecified margin and a design and analysis suitable for evaluating whether differences fall within that margin. The record does not report such a margin or an equivalence analysis. Nor does the interval establish a clinically important difference: the registry does not report a threshold for interpreting the magnitude of a change in pain score.

Thus, the most direct reading is that the estimated difference is -0.2, but the uncertainty around it is substantial enough that the posted data do not narrowly determine the direction or size of the between-group difference.

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 original trial design. Each row uses a stated fraction of that observed effect, and the columns express the number of participants per arm for 80% power and for 90% power. The figures are participants per arm, not total participants or total events. The outcome is continuous, so the time-to-event convention about total numbers of events does not apply.

The planning assumptions listed in the registry record are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record.

In general, power is the chance that a study design will detect an effect of a specified size under the assumptions used for planning, if that effect is present. The 80% column gives the planning number per arm for a design aimed at 80% power; the 90% column gives the corresponding number per arm for 90% power. These are design calculations, not summaries of what happened in the completed trial. They are not observed power.

The figures increase as the planning effect becomes smaller: planning for 75% or 50% of the observed effect requires more participants per arm than planning for 100% of it. In general, smaller effects are harder to distinguish from random variation, so more participants are needed to achieve the same planned power, all else equal.

Because the observed mean difference is close to zero, the illustrated participant counts are very large. These calculations depend on the assumptions listed and should not be read as a recommendation or as the study's original enrollment target. The actual recorded enrollment was 60 participants.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.200; pooled standard deviation σ = 3.253.
2. n = 2 × (1.96 + 0.842)² × 3.253² / -0.200² = 4,154.0, rounded up to 4,155 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 <- -0.2                      # observed difference in means
sigma <- 3.25345969699949                     # 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(2673372)
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 = 4,155 (80% power), 5,562 (90% power)
 75% of observed effect: n per arm = 7,385 (80% power), 9,887 (90% power)
 50% of observed effect: n per arm = 16,617 (80% power), 22,245 (90% power)
power.t.test: 4155 
Simulated power at n = 4,155 per arm: 0.801 (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.

13. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, time points, comparisons, or statistical analyses are examined. The more opportunities there are to find a small p-value, the greater the chance that at least one result may appear statistically notable by chance. General approaches include specifying a primary analysis in advance, adjusting for multiple comparisons, or clearly labeling exploratory analyses. The registry record lists one primary outcome measure and no posted secondary outcome measures, but it does not report whether a multiplicity adjustment was planned or used.

The record reports an unadjusted p-value of 0.812 for the primary comparison. No correction procedure is described. The available registry information does not establish whether other outcomes or analyses were considered outside the posted outcome record. Therefore, the reported p-value should be understood as unadjusted, without assuming that multiplicity was or was not addressed elsewhere.

Missing data can affect a trial result if outcome measurements are unavailable for some participants, especially if missingness is related to treatment or outcome. The posted group sizes are 30 participants each, matching the recorded enrollment of 60, but this alone does not describe the completeness of outcome collection or establish how missing data were handled. The record does not report missingness by group, reasons for missing observations, imputation, or sensitivity analyses.

Analysis populations also matter. An intention-to-treat analysis generally aims to analyze participants according to their randomized assignment, while a per-protocol analysis uses a population defined by adherence or other protocol criteria. The registry record does not identify the analysis population used for the posted primary outcome. It also does not describe exclusions after randomization or deviations from assigned treatment.

These omissions limit how fully the posted summary can be evaluated. They do not show that a particular problem occurred; they mean that the relevant procedures and details are not reported in the registry record.

14. 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 4% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 30 participants at risk in each group. It records zero serious adverse events in the morphine group and zero in the ketamine group. It also records zero deaths in each group. For other adverse events, it reports two affected participants among 30 at risk in each group.

These are descriptive counts as recorded in the registry. The serious-event figures indicate that no serious adverse events were posted for either group in this record; they do not establish that the treatments have identical safety profiles or rule out events that were not captured or reported. The record does not provide serious-event terms, and it does not give descriptions of the other adverse events.

Counts alone do not show event severity, timing, duration, recurrence, or whether an event was judged related to study treatment. The registry also does not report a formal statistical comparison of adverse events. With a small study population, the safety information is limited to the events recorded for these participants and should not be generalized into a comprehensive estimate of risk.

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

The posted primary outcome describes the average reduction in pain score at 30 minutes in the two study groups. The group means are 4.4 for morphine and 4.2 for ketamine. The reported ketamine-minus-morphine mean difference is -0.2, with a confidence interval from -1.846 to 1.446 and an unadjusted p-value of 0.812. Taken together, these statistics show that the estimated difference is small, but that the interval leaves considerable uncertainty about the direction and magnitude of the difference.

The result does not demonstrate that the treatments are equivalent. Equivalence requires a prespecified range of differences considered acceptably small and an analysis that evaluates the result against that range. Neither an equivalence margin nor an equivalence analysis is reported in the registry record. A p-value of 0.812 also does not prove there is no difference; it indicates that the posted analysis did not provide evidence against equal group means under its testing framework.

The result is specific to the posted endpoint and assessment time. It does not establish what happened at other times, how long any pain reduction lasted, or how other outcomes compared. The record lists no secondary outcome measures. It does not report baseline group values, the detailed method used to calculate change, or the handling of missing data and analysis populations.

The safety counts are also limited. The registry records no serious adverse events or deaths in either group and two participants with other adverse events in each group. These counts do not describe event details or support a broad conclusion about comparative safety.

The study's randomized design is a relevant strength for comparing assigned groups, but the registry record's limited analysis details constrain assessment of how the result was obtained. The posted data describe this study; they do not determine effects in other populations or settings, and they should not be read as medical advice.

16. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between a point estimate and the uncertainty around it. The estimated mean difference is -0.2, which is close to zero, but the confidence interval extends from -1.846 to 1.446. A small estimate does not by itself show that the true difference is small; the interval is essential for understanding how much uncertainty remains.

It also demonstrates why a non-significant result is not the same as evidence of equivalence. The unadjusted p-value is 0.812, and the confidence interval includes zero. Those features indicate that the analysis does not distinguish the group means, but they do not establish that the groups have the same effect. A formal equivalence question needs a clinically justified margin and an appropriate design, neither of which is reported in the registry record.

The study's size and observed variability matter for interpreting precision. There are 30 participants in each group, and the reported standard deviations are 3.1 and 3.4. The sample-size illustrations based on the observed effect require many participants per arm under their stated assumptions. This highlights how difficult it can be to plan a study around a very small observed contrast, and why planning assumptions should be selected before results are known rather than treated as proof after the fact.

Finally, statistical interpretation depends on transparent reporting. Details about missing data, analysis populations, baseline adjustment, and multiplicity are not reported in the registry record. Their absence does not demonstrate that the analysis was flawed, but it limits independent assessment of the result. Clear reporting of estimates, uncertainty, and analysis decisions is central to judging what a trial's data can support.

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.

The posted primary result has limited precision: its confidence interval runs from -1.846 to 1.446 and includes zero. The record reports 30 participants in each group, with standard deviations of 3.1 and 3.4. These values describe the available summary data, but they do not remove uncertainty about the true between-group difference.

The endpoint is described as reduction from baseline at 30 minutes, yet the registry does not post baseline group summaries or explain in detail how the reduction was calculated. It also does not identify whether the primary analysis adjusted for baseline values. This makes it difficult to independently assess the construction of the reported endpoint or distinguish a change-score analysis from other possible approaches.

Important design and analysis details are not reported in the registry record. These include the original sample-size justification, the randomization procedure, allocation concealment, which roles were masked, the primary analysis population, missing-data handling, and multiplicity procedures. The record does not report a protocol-defined threshold for a clinically meaningful difference, an equivalence margin, or a non-inferiority margin.

The outcome record includes one primary measure and no secondary outcomes. Consequently, the posted result gives a narrow view of the study's outcomes. The adverse-event record provides counts but not event descriptions, timing, attribution, or a comparative statistical analysis. The absence of reported serious events in the record should not be taken as a full accounting of safety.

These limitations concern the information available in the registry record. They do not establish that the trial lacked procedures or assessments that were not posted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Geriatric Ketamine for Pain Management Study — NCT02673372.
• Registry record last updated 2019-05-31; status last verified 2019-05.
• Results first posted 2019-05-31.
• 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 identifies NCT02673372 as the Geriatric Ketamine for Pain Management Study, a completed Phase 4 randomized parallel-group study with quadruple masking. Recorded enrollment was 60. The study compared intravenous ketamine at 0.3 mg/kg with intravenous morphine at 0.1 mg/kg, with a maximum morphine dose of 10 mg; both infusions were described as lasting 10 minutes.

The primary outcome was reduction of pain score at 30 minutes, measured using the NRS scale. The posted means were 4.4 for morphine and 4.2 for ketamine. The ketamine-minus-morphine mean difference was -0.2, with a confidence interval from -1.846 to 1.446 and an unadjusted p-value of 0.812.

The registry records zero serious adverse events and zero deaths in each group, with two participants in each group recorded as having other adverse events. Further details about those events and several aspects of the statistical analysis are not reported in the registry record.