Ketamine Patient-Controlled Analgesia for Acute Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine Patient-Controlled Analgesia for Acute Pain (NCT02062879), a randomized phase 3 study. The primary outcome is Total Daily Opioid Requirement.

2. Clinical Question

The trial description presents ketamine and hydromorphone as alternative patient-controlled interventions for trauma-related pain. Its brief summary lists expected differences across several additional clinical outcomes, including pain scores, oxygen-related measures, antiemetic use, bowel function, mobility, length of stay, opioid use at discharge, and chronic pain syndromes. Those statements describe expectations, not findings. The posted results do not give outcome values for those expectations. The named secondary outcomes are breakthrough daily opioid requirement and median pain score; results for them are not reported in the registry record.

The primary outcome focuses on opioid use rather than a direct pain rating. It therefore addresses the amount of opioid medication used per day, with medication amounts expressed on a common morphine-equivalent scale. It does not, on its own, establish how participants felt, whether analgesia was adequate, or how the groups compared on other outcomes.

3. Trial Design

The registry identifies this as a phase 3, randomized, triple-masked, parallel-group trial with an active comparator. It lists ketamine and hydromorphone as the two interventions and records an enrollment of 20. The posted primary outcome results include 10 participants in each arm. Randomization is a design feature intended to create groups comparable on average, while masking is intended to limit the influence of knowledge about assigned treatment on care, assessment, or reporting. The registry does not state who was masked or how masking was maintained.

The parallel design means participants were assigned to one intervention group rather than receiving both interventions in sequence. The active comparison is between two PCA drug regimens. The ketamine arm is recorded as ketamine 90mg/30 mL PCA (3 mg/mL), and the hydromorphone arm as hydromorphone 6mg/30 mL PCA (0.2 mg/mL). The registry does not provide further administration details, such as the permitted dosing schedule or adjustment rules; these are not reported in the registry record.

The study start is recorded as 2014-04 and primary completion as 2016-06. Its status is terminated. The registry record does not explain why the trial was terminated, whether recruitment reached its intended target, or whether termination affected follow-up or reporting. It records an enrollment of 20, but a planned enrollment target and any sample-size justification are not reported in the registry record.

Participants were to be followed for their entire hospital stay, with an expected average of 1 week. That is a stated expectation for follow-up duration, not a reported observed average. The registry does not provide individual follow-up durations, group-specific lengths of stay, or details of the timing of outcome collection. Although the trial has two named secondary outcomes and three outcome measures in total, it reports no analyses for them. The status and design describe how the study was set up, while the posted outcome summaries describe only a limited part of what was measured.

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

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Total Daily Opioid Requirement, measured over Participants will be followed for their entire hospital stay, an expected average of 1 week..

The primary endpoint is total daily opioid requirement, measured in milligrams of morphine equivalents per day. The registry defines it as daily breakthrough opioid requirement plus non-breakthrough opioid use. Converting opioid medications to morphine equivalents places different opioid amounts on a common scale for this outcome. The posted summary reports the median and inter-quartile range for each group.

A median describes the middle of the observed values after they are ordered. The inter-quartile range describes the spread from the lower quarter of observations to the upper quarter; it does not show every participant’s value. These summaries can be useful when individual observations are skewed or when a small number of values are far from the center. They offer a description of typical observed use and its distribution, but they are not, by themselves, a test of whether group outcomes differ beyond what might occur by chance.

In the ketamine group, the reported median was 10.0 mg morphine equivalents/day, with an inter-quartile range from 4.2 to 15.0. In the hydromorphone group, the median was 42.5 mg morphine equivalents/day, with an inter-quartile range from 31.7 to 62.0. The record does not give a confidence interval, a p-value, or an adjusted estimate for the difference between groups. It also does not state a separate assessment time within the hospital stay. This endpoint measures opioid requirement; it does not directly measure pain intensity, function, or overall clinical benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical concepts are explained generally in this discussion; they should not be mistaken for methods documented as used in this trial. The registry reports medians and inter-quartile ranges for the primary outcome, but does not report the statistical test, model, confidence interval method, or adjustment approach used for a between-group analysis. The concepts below clarify what the posted summaries can and cannot communicate.

What does the median describe?

General explanation: the median is the central observation in an ordered set of values. It is less influenced by extremely high or low observations than the arithmetic mean. For medication-use data, a few participants with especially large requirements can pull a mean away from the value typical of most participants; the median offers a different description of the center. It does not indicate how precisely that center has been estimated, and it does not describe all individual values.

The trial reports a median of 10.0 mg morphine equivalents/day for ketamine and 42.5 mg morphine equivalents/day for hydromorphone. These are group summaries. They do not show the values for each participant, and they do not establish that every participant in one group had a lower requirement than every participant in the other group. The registry record does not report a median difference or a confidence interval for a group contrast.

What does the inter-quartile range add?

General explanation: the inter-quartile range gives the interval between the lower and upper quartiles. It provides information about the middle portion of the observed distribution, complementing the median’s description of its center. It is not a confidence interval: it describes observed data spread, not uncertainty in an estimated treatment effect. Here the posted intervals are 4.2 to 15.0 for ketamine and 31.7 to 62.0 for hydromorphone. The record does not supply the individual observations or a further distributional summary.

Why might the analysis account for over-dispersion?

General explanation: over-dispersion occurs when the observed variation in data is greater than a statistical model assumes. If a model understates that variation, its uncertainty estimates can be too small and its inferential results can appear more precise than warranted. Models for counts, rates, or repeated measurements may need to account for extra variation when their assumptions do not fit the data. The posted primary endpoint is summarized as a median, and the registry record does not identify an analysis model or say that over-dispersion was assessed. It is therefore not possible to say whether it affected the trial’s analysis.

What would an interval estimate contribute?

General explanation: a confidence interval expresses uncertainty around an estimate under a specified statistical method. Its width reflects both the observed data and the method’s assumptions. An interval for a treatment contrast would help readers judge which values of the contrast remain compatible with the data under that method. The registry record does not report a confidence interval for the primary comparison, so the uncertainty around the group contrast cannot be read from the medians and inter-quartile ranges alone. The inter-quartile ranges must not be substituted for such an interval.

What does a hypothesis test contribute?

General explanation: a hypothesis test evaluates how compatible data are with a specified null hypothesis under a chosen model. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A test also depends on assumptions about the design, data, and analysis. No p-value or test result for the primary comparison is reported in the registry record. Thus the reported summaries cannot be described as statistically significant or not statistically significant on the basis of the registry results.

What role does randomization play?

General explanation: random assignment can reduce systematic differences between groups at the start of a trial, on average, when allocation is implemented as planned. It does not ensure that every characteristic will be balanced in a small sample. A prespecified analysis can also account for design features or baseline variables, but the variables and methods used for this trial are not reported in the registry record. The registry identifies the trial as randomized and parallel, but it does not give the sequence-generation or allocation-concealment procedures.

Masking can reduce opportunities for expectations to influence treatment delivery or outcome assessment. The registry labels masking as triple, but does not identify the masked roles, explain how the masking was maintained, or report whether it was successful. Those details should not be inferred from the label alone.

How should planning calculations be interpreted?

General explanation: a sample-size calculation uses assumptions about an outcome, a target effect, variability, allocation, and a chosen error rate to illustrate how much information a study might need. A planning illustration is not a result observed in the trial. It is not observed power, and it cannot establish the probability that the trial detected an effect. Any sample-size illustrations associated with this study should be read as planning scenarios based on their stated assumptions, not as outcomes or as evidence that the trial had adequate power. The registry does not report the trial’s own sample-size justification or target effect.

The study records 20 participants enrolled and 10 participants per arm in the posted primary result. With these summaries, the available evidence remains descriptive: a median and inter-quartile range for each group. More detailed interpretation would require an analysis plan and estimates of uncertainty, neither of which is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry names two secondary outcomes: breakthrough daily opioid requirement and median pain score. It also records three outcome measures in total, including the primary endpoint. The results of the secondary outcomes are not reported in the registry record. The brief summary lists additional expected outcomes, but does not provide their observed results. It is not reported whether the study tested all listed outcomes, which outcomes were prespecified as confirmatory, or how it handled the chance of false-positive findings when evaluating multiple outcomes.

Multiplicity is a general statistical concern when many outcomes or comparisons are tested. The more tests conducted, the greater the opportunity for at least one apparently unusual result to occur by chance, unless the analysis plan addresses that issue. The registry record does not report a multiplicity procedure or a hierarchy for interpreting outcomes. Since the secondary findings are not posted, their statistical interpretation cannot be assessed.

Information about missing data is also not reported in the registry record. It does not describe whether participants withdrew, whether any endpoint observations were unavailable, how missing values were handled, or whether sensitivity analyses were conducted. The posted primary summaries list 10 participants in each arm, but that count alone does not establish whether all randomized participants contributed data at every time point or how the analysis population was defined.

The record does not describe an intention-to-treat analysis, a per-protocol analysis, or another analysis population. It also does not report interim analyses, stopping rules, or whether any analysis decisions changed after the trial began. These details matter because they affect how readers assess the possibility of selective reporting and the relationship between the randomized groups and the analyzed participants. Their absence from the registry record should not be filled in by assumption.

11. 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 posted safety figures list serious adverse events for 0 of 10 participants in the ketamine group and 0 of 10 participants in the hydromorphone group. These counts describe what the registry records for the listed groups; they do not establish that no serious adverse events occurred outside the recorded information. The registry does not provide serious adverse event terms, and the deaths field is not reported in the registry record.

The record separately reports other adverse events affecting 7 of 10 participants in the ketamine group and 5 of 10 participants in the hydromorphone group. These are participant counts in the category labeled other adverse events, not counts of all event episodes. The registry does not list the terms for those events in the posted data. It also does not give an inferential comparison, event severity details for this category, or information on how event collection was conducted.

Zero recorded serious events in these small groups is not evidence that the risk is zero. Rare events may not appear in a limited sample, and the posted counts do not provide an estimate with an uncertainty interval. Similarly, the counts for other adverse events alone do not establish a causal difference between regimens. Safety interpretation should remain limited to the event counts and categories recorded; broader safety conclusions are not reported in the registry record.

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

The primary outcome results describe median daily opioid requirement during the hospital stay for participants assigned to ketamine PCA or hydromorphone PCA. The posted median is 10.0 mg morphine equivalents/day in the ketamine arm and 42.5 mg morphine equivalents/day in the hydromorphone arm. The corresponding inter-quartile ranges are 4.2 to 15.0 and 31.7 to 62.0. These values describe the observed groups, each with 10 participants in the posted primary result.

Those summaries do not establish the size or precision of a treatment effect. The registry record does not report a statistical test, confidence interval, adjusted estimate, or analysis method for the primary comparison. It is therefore not possible to determine from the posted results how compatible the observed group summaries are with a range of possible underlying differences, or whether the sponsor’s planned analysis supported a particular conclusion.

The endpoint is opioid requirement, not pain intensity. The registry lists median pain score as a secondary outcome, but its result is not reported in the registry record. The brief summary describes expected effects on numerous other outcomes, but expectations are not findings. Without posted results for those outcomes, the record cannot establish whether the groups differed in pain, oxygen-related measures, mobility, hospital course, or other aspects of recovery.

The record also does not establish that a difference in opioid use would translate into a difference in overall health or recovery. Such an interpretation would require results on relevant outcomes and an analysis that addresses uncertainty, along with sufficient details about how the trial was conducted. The sample size and terminated status provide important context, but the reason for termination and its consequences are not reported in the registry record.

In short, the posted values support a descriptive statement about the medians and observed spread for this trial’s participants. They do not by themselves establish a causal effect, a broader safety profile, or a conclusion about the overall balance of benefits and harms. Those questions remain unresolved by the results reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between group summaries and a complete comparative analysis. Medians and inter-quartile ranges show the observed center and middle spread of daily opioid requirements in the two groups. They are useful descriptions, but a reader also needs a between-group estimate and its uncertainty to judge how precisely the data distinguish among possible treatment effects. The registry record does not report those inferential results.

The study also illustrates why outcome definition matters. Total daily opioid requirement combines breakthrough and non-breakthrough opioid use and expresses the result in morphine equivalents per day. That is a specific measure of medication use, not a direct measure of pain or recovery. The brief summary names many expectations, while the primary result addresses only opioid requirement. Keeping these constructs separate avoids treating one outcome as a substitute for the others.

Randomization, masking, and an active comparator are important design features to note, but their labels do not answer every question about trial conduct. Details about allocation procedures, masked roles, the analysis plan, missing observations, and the reason for termination are not reported in the registry record. Such details help readers assess the credibility and scope of an estimate, especially when the posted outcome groups contain 10 participants each.

Finally, the trial shows why a posted descriptive result should not be confused with a complete evidence base. Secondary outcome results and inferential analyses are not reported. The group summaries can be described accurately, while the strength, precision, and broader meaning of a comparative conclusion remain uncertain. That distinction is central to careful interpretation of registry results.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The enrollment was 20, and the posted primary result includes 10 participants per arm. Such a small study offers limited information about the range of outcomes that might be observed in a larger population and provides little opportunity to characterize uncommon events. The registry does not state a planned enrollment target, the rationale for the target, or whether enrollment was intended to be larger before the trial was terminated.

The reason for termination is not reported in the registry record. Without that information, it is not possible to determine whether termination was related to recruitment, operational issues, safety, or another cause. Nor does the registry explain whether termination affected the planned analysis or completeness of follow-up.

The primary outcome is reported with a median and inter-quartile range for each group, but no between-group estimate, confidence interval, p-value, or analysis method. Consequently, the record does not quantify uncertainty around the comparison. No individual outcome data or baseline characteristics are reported in the posted registry entries, so the distributions and balance between the randomized groups cannot be examined beyond the posted summaries.

Secondary outcome results are not reported, despite the study description identifying breakthrough daily opioid requirement and median pain score as secondary outcomes. The broader expected outcomes listed in the brief summary also lack posted results. The registry does not report how multiplicity was handled, how missing observations were treated, or which participants were included in each analysis.

Important protocol and conduct details are absent, including eligibility criteria, allocation procedures, the identities of those masked, and an explanation of the terminated status. The expected average follow-up is 1 week over the entire hospital stay, but actual follow-up duration and completeness are not reported. These gaps limit evaluation of the primary result and prevent a fuller comparison of efficacy-related outcomes and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ketamine Patient-Controlled Analgesia for Acute Pain — NCT02062879.
• Registry record last updated 2017-09-21; status last verified 2017-08.
• Results first posted 2017-09-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry identifies NCT02062879 as a phase 3, randomized, triple-masked, parallel-group active-comparator trial of ketamine PCA versus hydromorphone PCA for acute pain in trauma patients. The recorded enrollment is 20, and the study status is terminated. The study start is 2014-04, and primary completion is 2016-06.

The primary outcome is median total daily opioid requirement in mg morphine equivalents/day over the hospital stay. The posted median is 10.0 for ketamine, with an inter-quartile range of 4.2 to 15.0, and 42.5 for hydromorphone, with an inter-quartile range of 31.7 to 62.0. The primary outcome groups each include 10 participants.

The registry lists breakthrough daily opioid requirement and median pain score as secondary outcomes, but their results are not reported in the registry record. It reports 0 serious adverse events among 10 participants in each arm; other adverse events affected 7 of 10 ketamine participants and 5 of 10 hydromorphone participants. No inferential analysis of the primary comparison, reason for termination, or explanation of missing outcome information is reported in the registry record.