This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Sub-dissociative Dose Ketamine Dosing Study (NCT03714620), a randomized phase 4 study. The primary outcome is Change in Pain Score From Baseline to 30 Minutes Post Initiation of Drug Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03714620 |
| Phase | Phase 4 |
| Condition | Acute Pain |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 98 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Loyola University |
| Results posted | Yes |
2. Clinical Question
Population
Adults presenting to the emergency department with moderate to severe acute pain were the intended population. The registry lists acute pain as the condition and records enrollment of 98 participants. It does not report further eligibility details, such as how pain severity was defined for enrollment or which patients were excluded.
Intervention
The lower-dose group received 0.15 mg/kg intravenous ketamine. The study goal described in the registry was to assess whether this dose would provide pain relief similar to the higher dose, with fewer adverse effects. The registry names ketamine as the drug intervention.
Comparator
The comparator was 0.3 mg/kg intravenous ketamine. The randomized, parallel-group design assigned participants to one of the two dose groups. The registry records 49 participants in each group for the primary endpoint.
Primary question
The primary endpoint was change in numerical pain score from time 0 to 30 minutes after drug administration. The study's stated aim was to compare the pain relief associated with the two doses and to consider whether the lower dose had fewer adverse effects. The registry does not report a formal comparison analysis for the primary endpoint, a definition of what would count as similar pain relief, or a prespecified threshold for a clinically meaningful difference.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group trial registered as NCT03714620. The registry identifies it as Phase 4 and lists Loyola University as sponsor. Enrollment was 98 participants, with 49 recorded in each dose group for the primary endpoint. The trial status is completed. The recorded start date is 2018-10-15, and the primary completion date is 2019-09-17.
The two groups received intravenous ketamine at 0.15 mg/kg or 0.3 mg/kg. A parallel-group design assigns each participant to one group rather than having participants receive both study doses in sequence. Random assignment is intended, in general, to make the groups comparable at the start of the study, apart from chance variation. The registry does not report the randomization method or allocation concealment procedures.
Quadruple masking indicates that the registry classified the study as masking four roles, but the identities of those roles and the practical masking procedures are not reported in the registry record. The arm descriptions contain no additional details. The registry does not state the planned treatment schedule, accompanying care, adherence, or whether participants could receive other pain treatments outside the listed rescue-medication outcomes.
The registry lists six outcome measures and names change in pain score at 30 minutes as the primary endpoint. It also lists secondary outcomes covering pain-score change at 15 and 60 minutes, additional or rescue pain medication, and adverse effects. Numeric secondary results are posted for the two medication-use outcomes; the other listed secondary outcomes have no numeric results in the registry record. No reported analyses are listed for the primary endpoint or for the posted secondary outcomes.
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
| Stage | Low Dose Group | High Dose Group |
|---|---|---|
| STARTED | 49 | 49 |
| COMPLETED | 49 | 49 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | 0.15 mg/kg IV Ketamine | 0.3 mg/kg IV Ketamine | Total |
|---|---|---|---|---|
| Participants analysed | 49 | 49 | 98 | |
| Age, Continuous | years | 39 (36 to 42) | 37 (34 to 41) | 38 (34 to 42) |
| Sex: Female, Male: Female | Participants | 30 | 27 | 57 |
| Sex: Female, Male: Male | Participants | 19 | 22 | 41 |
| Race/Ethnicity, Customized: Race – African American | Participants | 15 | 13 | 28 |
| Race/Ethnicity, Customized: Race – White | Participants | 18 | 28 | 46 |
| Race/Ethnicity, Customized: Race – Other | Participants | 16 | 8 | 24 |
| Region of Enrollment: United States | Participants | 49 | 49 | 98 |
| Co-morbidities: Diabetes | participants | 13 | 3 | 16 |
| Co-morbidities: Hypertension | participants | 13 | 8 | 21 |
| Co-morbidities: Cancer | participants | 1 | 1 | 2 |
| Co-morbidities: Anxiety | participants | 1 | 7 | 8 |
| Co-morbidities: Heart Failure | participants | 2 | 1 | 3 |
| Co-morbidities: Depression | participants | 3 | 10 | 13 |
| Co-morbidities: Obesity | participants | 11 | 9 | 20 |
| Weight | kilograms | 85 (81 to 90) | 84 (80 to 89) | 84 (80 to 90) |
| Type of Pain: Flank | Participants | 6 | 4 | 10 |
| Type of Pain: Back | Participants | 4 | 2 | 6 |
| Type of Pain: Musculoskeletal | Participants | 14 | 16 | 30 |
| Type of Pain: Headache | Participants | 2 | 4 | 6 |
| Type of Pain: Abdominal | Participants | 23 | 23 | 46 |
| Duration of Pain: <24 hours | Participants | 21 | 28 | 49 |
| Duration of Pain: 2 days | Participants | 9 | 9 | 18 |
| Duration of Pain: 3-7 days | Participants | 19 | 12 | 31 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Pain Score From Baseline to 30 Minutes Post Initiation of Drug Administration, measured over 30 minutes.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change in numerical pain score from baseline, recorded at time 0, to 30 minutes after initiation of drug administration. The registry describes the numerical rating scale as ranging from 0 to 10, with higher scores indicating more pain. It reports the endpoint as a mean with a 95% confidence interval. A change score is intended to represent how a participant's measured pain score differs between the two specified assessment times.
Assessing pain at a defined time after treatment gives the study a common time point for comparing the two dose groups. A mean summarizes the average change within a group, while the confidence interval expresses uncertainty around that group mean. It does not describe the range of changes among individual participants. The registry's endpoint description does not state how the direction of the change score is coded, so the reported positive means should not be labeled as pain reduction or worsening based on the record alone.
The primary endpoint could support a comparison of average change between doses if a between-group estimate and its uncertainty were reported. The registry posts an estimate and confidence interval for each group separately, but no primary between-group estimate, confidence interval for that contrast, or p-value. It also does not report a threshold defining a meaningful difference or a margin for concluding that the doses provide similar pain relief.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a mean primary-endpoint change of 3.8 for the 0.15 mg/kg group, with a 95% confidence interval from 3.0 to 4.7. For the 0.3 mg/kg group, it reports a mean of 3.5, with a 95% confidence interval from 2.7 to 4.3. Each group had 49 participants recorded for this endpoint. These are arm-level summaries, not a reported estimate of the difference between doses.
The intervals describe uncertainty around each group's mean under the statistical method used to construct them. Their overlap does not establish that the dose groups are equivalent, nor does it show that a difference is absent. A direct estimate of the between-group contrast, with its uncertainty, is needed to assess how compatible the results are with different possible dose effects. Such a primary comparison is not reported in the registry record. The direction of the change score is also not specified, so the positive values cannot be interpreted from the record alone as improvement or worsening.
The stated study goal includes whether the lower dose provides similar pain relief with fewer adverse effects. Similarity or equivalence requires a defined margin and a suitable analysis; neither is reported in the registry record. A non-significant test, even if one had been reported, would not by itself establish similarity. Here, no primary p-value or formal comparison is posted, so the primary endpoint supports only a description of the reported means and their separate intervals.
The posted secondary medication-use outcomes report low counts. At 30 minutes, additional pain medication was recorded for 1 participant in the 0.15 mg/kg group and 0 in the 0.3 mg/kg group; the unadjusted risk difference for 0.3 mg/kg versus 0.15 mg/kg was -0.020, with a 95% confidence interval from -0.06 to 0.019 and p = 0.315. At 60 minutes, rescue medication was recorded for 2 and 4 participants, respectively; the risk difference was 0.041, with a 95% confidence interval from -0.054 to 0.135 and p = 0.399. Both intervals include no difference and extend across effects in either direction. The small counts also mean that these estimates are imprecise.
These secondary findings do not replace the missing primary between-group analysis. They are unadjusted secondary comparisons, and the registry does not report a multiplicity plan. The posted information therefore supports a cautious description of the recorded outcomes, not a definitive conclusion about relative dose effects or about whether the study's stated similarity goal was met.
9. Statistical Methods Explained
The primary endpoint is continuous: it is a numerical pain-score change summarized by a mean. The registry reports one mean and one 95% confidence interval for each dose group. A confidence interval is a statistical range that expresses the uncertainty associated with an estimated quantity under the method's assumptions. It is not a range containing a stated proportion of individual participants' scores, and it is not itself a direct comparison of the groups.
What does the primary confidence interval tell us?
Each interval concerns its group's mean change. It gives an indication of how precisely that mean is estimated, while the width reflects uncertainty. To answer a comparative question, the relevant quantity would ordinarily be the difference in mean change between the two randomized groups, together with an interval or other inferential result for that difference. Separate arm-level intervals cannot substitute for that contrast. The registry does not report a primary contrast, its confidence interval, or a p-value.
The record says the endpoint is the change from time 0 to 30 minutes but does not specify the sign convention used to calculate change. Although the scale description states that higher scores indicate more pain, that alone does not identify whether a positive change means an increase or a decrease in pain. The numeric means should therefore be presented without assigning a direction of benefit.
How should the secondary risk differences be read?
For each posted medication-use outcome, the risk difference is expressed as the proportion in the 0.3 mg/kg group minus the proportion in the 0.15 mg/kg group. A negative estimate indicates a lower observed proportion in the higher-dose group; a positive estimate indicates a higher observed proportion there. The 30-minute estimate is -0.020, and its confidence interval ranges from -0.06 to 0.019. The 60-minute estimate is 0.041, and its interval ranges from -0.054 to 0.135. Both intervals include zero, the value representing no difference in proportions.
The associated p-values, 0.315 and 0.399, are labeled unadjusted in the posted results. A p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions apply. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry lists no reported analysis methods for these outcomes, so the posted unadjusted p-values should not be read as evidence that a multiplicity procedure was applied.
Why do the small counts matter?
When outcomes are uncommon, each additional event can noticeably affect the estimated proportion and the between-group contrast. General statistical principle: sparse event counts often produce substantial uncertainty, which is visible in the wide intervals for these risk differences. The 30-minute outcome records only 1 and 0 participants, and the 60-minute outcome records 2 and 4 participants. These counts do not support highly precise estimates of differences in medication use.
What do the planning illustrations mean?
The registry's planning assumptions describe an illustration based on the observed effect, not the design calculation for this trial. They specify a two-sided significance level of 0.05, equal allocation, and a normal approximation, with alternative scenarios based on 100%, 75%, or 50% of the observed effect. The listed results are participants per arm. Such illustrations show how a target effect and design assumptions relate to a potential sample size. They do not represent observed power, do not show that the original study was designed around those assumptions, and do not establish whether an effect is real. The trial's own sample-size justification is not reported in the registry record.
The registry identifies no reported analyses for the primary or secondary outcomes. It also does not report whether the primary analysis used an intention-to-treat or another analysis population, how missing outcome data were handled, which model produced the primary confidence intervals, or whether any covariate adjustment was planned. Those details cannot be inferred from the posted means and counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcome measures, including the primary pain-score change at 30 minutes and secondary measures at other time points, medication-use outcomes, and adverse effects. It reports no primary or secondary analyses in its analysis listings. The two posted medication-use comparisons include unadjusted p-values, but no plan for multiple testing is reported in the registry record.
Multiplicity matters because drawing conclusions from several statistical tests increases the chance that at least one result appears noteworthy by chance alone. General statistical principle: interpretation depends on whether outcomes and analyses were selected in advance and whether a strategy was planned for controlling or describing that risk. The record does not report a testing hierarchy, adjustment method, or distinction between confirmatory and exploratory secondary analyses. The unadjusted p-values should therefore be treated as individual, unadjusted comparisons, not as a multiplicity-controlled assessment of all outcomes.
The registry does not report the number of participants with observed primary endpoint data beyond the arm counts shown, the amount or pattern of missing data, or how missingness was handled. It does not state whether any values were imputed, whether analyses used complete cases, or whether sensitivity analyses were conducted. Missing-data methods can affect both estimates and uncertainty, especially if the availability of measurements is related to participants' outcomes. No particular missing-data approach can be assumed.
The analysis population is also not reported. The registry does not state whether all randomized participants were included in the primary analysis, whether participants were analyzed according to assigned dose, or whether exclusions occurred after randomization. These details matter because analysis populations can alter the interpretation of a randomized comparison.
There is no reported primary comparison estimate or inferential analysis, no stated similarity margin, and no reported sample-size justification. The record also does not report interim analyses or a detailed statistical analysis plan. These omissions do not establish that such procedures were absent; they mean only that they are not reported in the registry record. The posted results should be interpreted within those limits.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 0.15 mg/kg IV Ketamine | 0 | 49 | 0.0% |
| 0.3 mg/kg IV Ketamine | 0 | 49 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 0.15 mg/kg IV Ketamine | 0 of 49 |
| 0.3 mg/kg IV Ketamine | 0 of 49 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 0.15 mg/kg IV Ketamine | 28 of 49 |
| 0.3 mg/kg IV Ketamine | 31 of 49 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 0.15 mg/kg IV Ketamine | 0.3 mg/kg IV Ketamine |
|---|---|---|---|
| Fatigue | General disorders | 18 of 49 | 20 of 49 |
| Dizziness | Nervous system disorders | 21 of 49 | 16 of 49 |
| Discomfort | General disorders | 16 of 49 | 21 of 49 |
| Headache | General disorders | 16 of 49 | 11 of 49 |
| Feeling of Unreality | General disorders | 8 of 49 | 6 of 49 |
| Vision Changes | Eye disorders | 4 of 49 | 6 of 49 |
| Mood Alteration | Psychiatric disorders | 4 of 49 | 6 of 49 |
| Hallucinations | Psychiatric disorders | 2 of 49 | 3 of 49 |
| Hearing Changes | Ear and labyrinth disorders | 0 of 49 | 2 of 49 |
The safety summary records serious adverse events for 0 of 49 participants in the 0.15 mg/kg group and 0 of 49 participants in the 0.3 mg/kg group. It also records 0 deaths in each group. These are the serious-event and death counts posted for the two groups; the registry does not list serious-event terms.
Zero recorded events in both groups means that no serious adverse events or deaths are counted in these posted summaries. It does not prove that the underlying risk is zero, nor does it establish that serious-event risks are the same between doses. When no events are observed, the data provide limited information about uncommon events, and the registry does not report a comparative safety analysis or confidence intervals for these counts.
The record separately reports other adverse events affecting 28 participants in the lower-dose group and 31 participants in the higher-dose group, with 49 participants at risk in each group. Those counts are distinct from the serious adverse event counts. The record does not provide the terms, severity breakdown, event-level counts, or a statistical comparison for these other adverse events in the posted safety summary. They should not be combined with the serious-event figures or treated as evidence of a dose difference without further detail.
12. What the Result Does, and Does Not, Mean
The registry describes a randomized comparison of two ketamine doses and reports the mean change in pain score for each group at 30 minutes. The means are 3.8 for 0.15 mg/kg and 3.5 for 0.3 mg/kg, with separate 95% confidence intervals. The record does not post the primary between-group estimate or its uncertainty. The numeric summaries therefore do not by themselves answer whether the groups differed, how large any difference may be, or whether the doses provided similar pain relief.
The study's stated objective included whether the lower dose could provide similar pain relief with fewer adverse effects. A conclusion of similarity requires a prespecified margin that defines how much difference would still count as similar and an analysis designed to assess that margin. Neither is reported in the registry record. Similar-looking arm means or overlapping separate confidence intervals cannot replace such an analysis.
The secondary medication counts offer limited additional information. Their unadjusted confidence intervals include no difference and also allow effects in either direction. Because the event counts are small, estimates are imprecise. The other listed secondary outcomes do not have numeric results in the registry record, and the record does not describe a multiplicity plan. Together, these limits mean the secondary outcomes cannot establish a comprehensive pattern across pain scores, medication use, and adverse effects.
The absence of serious adverse events and deaths in the posted counts should be read as zero observed events in the recorded groups, not as proof of no risk. The counts of other adverse events are also reported, but the registry does not give their terms or a comparative analysis.
More broadly, registry results are an account of what is posted in the record. The record does not provide the detailed analysis population, missing-data approach, primary comparison method, or sample-size justification needed to fully assess the precision and robustness of the findings. These limitations constrain interpretation; they do not establish that unreported analyses or procedures were not conducted.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between reporting results for each group and reporting a comparative treatment effect. The primary endpoint is presented with a mean and confidence interval for each dose, but the registry does not report a direct estimate of the difference between doses. A reader can describe the group summaries, but cannot use them alone to quantify the primary contrast with its uncertainty.
The study's stated goal concerns similarity between doses, which is not established simply by observing estimates that appear close or intervals that overlap. A formal similarity or equivalence question depends on a prespecified margin and an appropriate analysis. Because neither is reported, the posted primary results do not resolve the stated comparison.
The secondary outcomes also demonstrate how sparse data affect interpretation. The medication-use outcomes involve few participants, and their intervals are broad enough to include no difference and effects in either direction. This is a precision issue: the observed counts can be reported exactly, while the underlying difference remains uncertain. A non-significant p-value does not make that uncertainty disappear.
Finally, the record lists multiple outcome questions but does not report a multiplicity strategy, missing-data handling, or analysis population. These are central considerations when interpreting a randomized trial, particularly when the posted results do not include a primary contrast. The planning illustrations are also distinct from the actual trial design: they are based on the observed effect under stated assumptions and should not be treated as observed power or evidence that the study was planned to detect a particular effect.
For biostatistical interpretation, the key lesson is to separate what is directly reported from what would require an unreported analysis. The record supports careful description of arm-level outcomes and selected counts; it does not support a definitive conclusion about comparative primary efficacy, similarity, or relative safety.
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.
Several limitations are specific to the information posted for this trial. Most importantly, the primary endpoint has group-level means and confidence intervals but no reported between-group contrast, confidence interval for the contrast, or p-value. That leaves the central comparison less directly interpretable than the study objective suggests. The registry also does not specify the direction convention for the change score, so the positive values cannot be confidently described as reductions in pain.
The secondary outcome record is incomplete relative to the listed measures. Numeric results are available for additional pain medication at 30 minutes and rescue medication at 60 minutes, but not for the listed pain-score changes at 15 and 60 minutes or adverse effects at 30 minutes. The two available medication-use outcomes have few events and imprecise estimates. The registry does not report the details behind the other adverse-event counts.
Important design and analysis details are not reported in the registry record: the sample-size justification, the method used to analyze the primary endpoint, the analysis population, the handling of missing data, and any multiplicity strategy. The record also does not give detailed eligibility criteria, randomization procedures, allocation concealment, the roles covered by quadruple masking, or additional arm-specific treatment details. These omissions limit assessment of the trial's conduct and the robustness of the posted results.
These are limitations of what can be established from the registry record, not proof that the trial lacked procedures or analyses that are not described there. No conclusions about adherence, outcome completeness, or the reasons for missing secondary results can be drawn from the posted information alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sub-dissociative Dose Ketamine Dosing Study — NCT03714620.
- Registry record last updated 2022-08-09; status last verified 2022-08.
- Results first posted 2022-08-09.
- 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.
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18. Record Summary
NCT03714620 is a completed Phase 4 randomized, quadruple-masked, parallel-group trial sponsored by Loyola University. It enrolled 98 participants and compared 0.15 mg/kg intravenous ketamine with 0.3 mg/kg intravenous ketamine. The recorded start date is 2018-10-15, and primary completion was recorded as 2019-09-17.
The primary outcome was mean change in numerical pain score from baseline to 30 minutes. The registry reports a mean of 3.8 with a 95% confidence interval from 3.0 to 4.7 for the lower dose, and a mean of 3.5 with a 95% confidence interval from 2.7 to 4.3 for the higher dose. It does not report a primary between-group analysis. Two secondary medication-use outcomes include unadjusted comparisons; other listed secondary results are not reported in the registry record.
Serious adverse events and deaths are recorded as 0 in each group. Other adverse events are recorded for 28 participants in the lower-dose group and 31 in the higher-dose group. The registry does not report the sample-size justification, analysis population, missing-data approach, or multiplicity plan.