Ketamine for Acute Migraine in the Emergency Department: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine for Acute Migraine in the Emergency Department (NCT02697071), a randomized na study. The primary outcome is Achievement of Pain Response After Ketamine Dose..

2. Clinical Question

The clinical question is whether the recorded pain-score changes differ between the ketamine and saline groups at the specified assessment time. This is a question about a comparative treatment effect, rather than whether pain scores changed within either group alone. A placebo group helps separate changes associated with study participation, time, and other care from changes associated with the study medication, but a comparative conclusion still requires an appropriate between-group analysis.

The registry lists enrollment as 34. The primary outcome results include 18 participants in the placebo group and 16 in the ketamine group. The record does not explain whether the outcome population differs from the enrolled population or why any participants might be absent from an analysis. It also does not give further detail about the emergency-department population, the diagnosis process, or how acute migraine-type headache was defined for eligibility.

3. Trial Design

NCT02697071 is a completed randomized, placebo-controlled clinical trial of sub-dissociative ketamine for acute migraine-type headache in the emergency department. The registry describes a parallel-group model and triple masking. The brief summary calls the study double-blind. The record does not explain this difference in masking descriptions, so the exact roles of the people masked cannot be established from the registry record.

Participants were assigned to ketamine or placebo. The ketamine arm received 0.2mg/kg intravenously over one minute, while the placebo arm received an equivalent volume of normal saline intravenously. This design permits a comparison between the groups, but the registry's posted primary outcome figures are descriptive summaries rather than a reported inferential comparison.

The registry lists enrollment as 34, with the primary outcome reported for 18 participants in the placebo group and 16 in the ketamine group. The study start is listed as 2016-02, and primary completion as 2017-03; the status is completed. The phase is recorded as NA. The sponsor is Carilion Clinic.

The registry record does not report the method used to generate the randomization sequence, allocation concealment, the precise masking procedures, protocol deviations, or the planned statistical analysis. It also does not report a sample-size justification or a target power. These details may matter when judging how well the design supports a causal comparison, but they cannot be inferred from the randomized and masked labels alone.

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 Achievement of Pain Response After Ketamine Dose., measured over 30 minutes.

The primary endpoint is achievement of pain response after the ketamine dose, represented in the registry as change in NRS (National rating scale) pain score from baseline at 30 minutes. The scale ranges from 0 to 10, with higher scores indicating worse pain. The outcome is summarized using the median and inter-quartile range for each group.

A pain score is a direct, patient-reported measure of symptom intensity. Assessing change from baseline can focus attention on how reported pain differs from the participant's starting score, rather than only comparing scores at follow-up. A fixed assessment time also makes the timing of the group summaries explicit. These are general reasons such measures may be used; the registry does not state why this particular endpoint or assessment time was selected.

The reported medians are 2.0 for placebo and 1.0 for ketamine. The inter-quartile ranges are 0.0 to 3.75 and 0.0 to 2.25, respectively. However, the registry does not specify whether change was calculated as baseline minus follow-up or follow-up minus baseline. Because that sign convention is not reported, the direction represented by a positive change cannot be determined from the record alone. The scale's higher-is-worse description does not resolve that ambiguity.

The outcome is a group-level summary and does not show every participant's score or the distribution's full shape. The registry does not give a responder threshold, such as a defined amount of change that qualifies as a response. Nor does it report a confidence interval for the median or for a between-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how an observed group difference is estimated and how much uncertainty surrounds it. The registry identifies a randomized parallel-group design and reports group-level medians and inter-quartile ranges for the primary endpoint. It does not report the primary-outcome analysis method, a between-group estimate, a confidence interval, or a p-value. The explanations below describe general statistical concepts, not methods confirmed as used in this trial.

Why compare groups directly?

In a randomized trial, the central question is usually whether outcomes differ between assigned groups. A comparison of each group's change from baseline, considered separately, is not equivalent to a comparison of the groups. People can improve or worsen over time for reasons unrelated to the assigned intervention. A between-group analysis is designed to estimate the contrast that addresses the randomized comparison. The registry provides separate group summaries but does not report such a contrast for the primary outcome.

What does a median show?

The median is the middle of an ordered set of observations. It describes a typical location without relying on the arithmetic mean and can be useful when scores are skewed or include unusual values. The inter-quartile range describes the span between the lower and upper quartiles, giving information about the spread of the middle portion of observations. These summaries do not reveal the full distribution or the precision of a treatment-effect estimate.

The registry reports median change scores of 2.0 for placebo and 1.0 for ketamine, with respective inter-quartile ranges of 0.0 to 3.75 and 0.0 to 2.25. Those summaries should be read alongside the endpoint definition. Since the registry does not specify the order used to calculate change, the sign cannot safely be translated into improvement or worsening.

What would a confidence interval contribute?

In general, a confidence interval presents a range of values compatible with an estimate under the method's assumptions. It helps readers assess precision as well as the estimate's direction and size. A narrow interval generally indicates greater precision than a wide interval, although interpretation also depends on the outcome and analysis. No confidence interval is reported for the primary between-group effect in this registry record. The inter-quartile ranges are not confidence intervals: they describe variation among observed scores, not uncertainty in the estimated comparison.

What does a p-value answer?

In general, a p-value measures how unusual data at least as extreme as those observed would be under a specified null hypothesis and statistical model. It does not measure the probability that the null hypothesis is true, and it does not indicate whether an effect is important. The registry record does not report a p-value for the primary comparison. Without the analysis specification and its result, no significance conclusion can be drawn from the medians alone.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a model understates variability, uncertainty estimates may be too small and statistical tests may be misleading. The primary endpoint is a score-change outcome summarized by medians and inter-quartile ranges; the record does not identify a fitted model or describe over-dispersion. It would therefore be inappropriate to claim that over-dispersion was assessed or to select a model on the trial's behalf.

How should planning illustrations be read?

General statistical explanation: a sample-size calculation uses assumptions about a target effect, variability, significance level, allocation, and analysis method to illustrate the amount of information a future study might require. It is a planning exercise, not an observed trial result and not a measure of the probability that this completed trial detected an effect. The registry's planning description specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. It also distinguishes total events for time-to-event calculations from participants per arm for other calculations. The record does not report the trial's own sample-size justification or target power. No planning count should be treated as observed power.

What cannot be reconstructed?

Recalculating an inferential comparison would require details that are not reported, including an unambiguous change-score convention and a suitable account of the underlying observations and their distribution. Group medians and inter-quartile ranges do not determine all participant-level values or a unique standard error for a between-group effect. Since the registry reports no analysis and no sponsor comparison, no recalculated inferential result is warranted from the posted summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary pain-response outcome and one secondary outcome, categorical pain-score change from baseline. It also reports three outcome measures, but no analyses are listed. The record does not describe a multiplicity strategy, such as a prespecified hierarchy or adjustment of significance thresholds. Without that information, the protection against false-positive findings across multiple outcomes cannot be assessed.

The registry gives group counts for the primary outcome, but does not describe missing observations, exclusions, or reasons that outcome data might be unavailable. It does not state whether the reported summaries use an intention-to-treat population, a per-protocol population, or another analysis population. The enrollment figure is 34, while the primary outcome summaries list 18 placebo participants and 16 ketamine participants; the record does not explain the relationship between enrollment and the reported outcome populations.

These omissions matter because missingness and analysis-population choices can affect both the estimated effect and its uncertainty. For example, if outcome availability is related to participants' symptoms or treatment assignment, analyzing only available observations may not preserve the balance created by randomization. That is a general concern, not a claim about what happened in this trial.

The registry does not report a statistical analysis plan, handling of missing outcome data, or prespecified rules for selecting among analyses. As a result, readers cannot determine whether the posted summaries reflect the planned analysis or how multiplicity and missing data were handled.

11. 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 0% reporting threshold.

The registry reports zero serious adverse events in the placebo group, among 18 participants at risk, and zero in the ketamine group, among 16 participants at risk. It also reports zero other adverse events in each group, and zero deaths in each group. These figures describe events recorded in the registry during the reported safety assessment; they are not estimates of the chance of an event in a broader population.

A zero count means no event of that listed category was reported among the participants at risk in that group. It does not establish that the underlying risk is zero. When events are uncommon, a study may observe no events while still leaving substantial uncertainty about the rate that could occur in other settings or with more observation. Quantifying that uncertainty would require an appropriate interval or model, neither of which is reported.

The record does not provide details about the adverse-event collection period, definitions, severity grading, or completeness of follow-up. The serious-event figures should therefore be read as counts in the registry, not as a comprehensive safety comparison. They do not establish that the treatments have equivalent safety profiles or that clinically important harms are absent.

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

The results establish that the registry posted median pain-score changes and inter-quartile ranges for the placebo and ketamine groups at 30 minutes. They also establish the recorded adverse-event counts: no serious adverse events, other adverse events, or deaths are listed in either group. These are observations in the registry record, not a complete account of every possible outcome or later evidence.

The reported pain summaries do not establish a treatment effect. No inferential comparison, confidence interval, or p-value is reported for the primary endpoint. Moreover, the record does not say whether change was calculated by subtracting the baseline score from the follow-up score or vice versa. The direction of the median change values cannot therefore be interpreted as improvement or worsening from the scale description alone.

The findings also do not show how outcomes varied for individual participants, whether the groups differed in important baseline characteristics, or how many observations were missing. The registry does not report the analysis population, the statistical plan, or a sample-size justification. Those gaps limit assessment of precision, risk of bias, and whether the analysis followed a prespecified approach.

The randomized, placebo-controlled design is relevant to evaluating a comparative effect, but a design cannot supply an unreported estimate. Likewise, zero recorded adverse events do not demonstrate zero risk, and they do not establish equal safety between groups. A small set of observed counts can be compatible with uncertainty about uncommon outcomes.

In statistical terms, the posted results are descriptive and incomplete for judging comparative efficacy or safety. They can be reported as the registry presents them, with the score-change convention and inferential analysis clearly identified as not reported. They should not be turned into a claim that ketamine works, does not work, or has a particular safety profile.

13. Why This Trial Matters Statistically

This trial matters statistically because it uses randomization and a placebo comparator to frame a focused question about pain-score change after an intravenous intervention in emergency-department patients with acute migraine-type headache. The primary endpoint is assessed at a stated time, 30 minutes, and summarized by group. These features make the intended comparison identifiable in principle.

At the same time, the record illustrates why descriptive summaries are not enough to answer a comparative research question. Medians and inter-quartile ranges show locations and spread in the observed scores, but they do not quantify the between-group effect or its precision. Without a reported change-score convention, the direction of the values is also ambiguous. Clear endpoint definitions and a direct treatment contrast are essential for statistical interpretation.

The safety figures are another example of how counts need context. Zero events are observations, not proof of no risk. Interpretation depends on event definitions, follow-up, completeness, and uncertainty, details the registry record does not provide.

The trial also highlights the role of transparent analysis reporting. A statistical plan, missing-data approach, analysis population, and multiplicity strategy help readers distinguish prespecified conclusions from exploratory ones. The registry does not report those details or a primary inferential result. Their absence limits what can be learned from the posted record even though the trial's randomized design is described.

These issues are important to biostatisticians and clinical researchers because sound interpretation depends on both design and reporting. The record offers a basis for describing the observed summaries, while leaving the central comparative estimate and its uncertainty unreported.

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 main limitation of the posted primary result is that it reports group medians and inter-quartile ranges without a between-group effect estimate, confidence interval, or p-value. The registry also does not specify the subtraction order for change from baseline, preventing an unambiguous interpretation of direction.

The outcome counts listed are 18 in the placebo group and 16 in the ketamine group, while enrollment is recorded as 34. The registry does not explain whether all enrolled participants contributed to the primary outcome, whether any data were missing, or how analysis populations were defined. It does not report baseline characteristics or participant-level scores, so the distributions and comparability of the analyzed groups cannot be assessed from these results.

Several design and analysis details are not reported: randomization sequence generation, allocation concealment, the practical masking procedures, a statistical analysis plan, the method for handling missing data, and any multiplicity approach. The registry's masking label is triple, whereas its brief summary describes a double-blind study; the record does not reconcile those descriptions.

The endpoint is described as pain-score change at 30 minutes, but the record does not state a responder threshold or give details on measurement procedures. Safety reporting lacks further information about definitions, observation period, and completeness. These limits concern the registry record and do not establish that the underlying study lacked these methods or data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ketamine for Acute Migraine in the Emergency Department — NCT02697071.
• Registry record last updated 2021-03-26; status last verified 2021-03.
• Results first posted 2021-02-25.
• 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

NCT02697071 is a completed randomized, parallel-group, placebo-controlled trial sponsored by Carilion Clinic. It studied sub-dissociative ketamine for acute migraine-type headache in the emergency department. The registry lists enrollment as 34 and reports the study start as 2016-02 and primary completion as 2017-03.

The ketamine group received 0.2mg/kg intravenously over one minute; the placebo group received an equivalent volume of normal saline intravenously. The primary outcome was change in NRS pain score from baseline at 30 minutes, summarized by medians and inter-quartile ranges. The registry does not state the change-score sign convention or report an inferential comparison.

The record lists one secondary outcome and three outcome measures, with no analyses listed. It reports zero serious adverse events, zero other adverse events, and zero deaths in both groups. Further information on missing data, analysis populations, statistical methods, and sample-size justification is not reported in the registry record.