The Sustained Effects of Ketamine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Sustained Effects of Ketamine (NCT02708849), a randomized phase 1 study. The primary outcome is Post-Ketamine Rs-fMRI Data.

2. Clinical Question

3. Trial Design

The registry identifies NCT02708849, titled The Sustained Effects of Ketamine. It is listed as a phase 1, randomized, double-masked, parallel study sponsored by Yale University. The listed arms are Ketamine Plus Lamotrigine and Ketamine Plus Placebo. The interventions are named as ketamine, lamotrigine and placebo. The brief summary describes the purpose as characterizing effects of a single, sub-anesthetic dose of ketamine in healthy subjects.

Enrollment was 3. The study start is recorded as 2015-06, and primary completion as 2020-03. Its status is TERMINATED. The reason for termination is not reported in the registry record, so the status alone does not explain why recruitment or study activity ended, whether the planned study was completed, or how the observed enrollment related to the intended enrollment.

The registry lists Mental Disorders under conditions, while the brief summary describes healthy subjects. The record does not explain this difference. It also does not report detailed eligibility criteria, allocation procedures, masking procedures, treatment schedule, dose, or the planned duration of participant follow-up beyond the primary outcome timeframe. Those details should not be inferred from the study title or design labels.

A randomized, double-masked, parallel design describes how a study is organized, not what its results show. Randomization is generally used to reduce systematic differences between treatment groups, while masking is generally intended to limit effects of knowing treatment assignment on care or assessment. The registry does not provide enough procedural detail to evaluate how either feature was implemented in this study. With enrollment of 3 and without reported outcome data, the design labels do not establish the precision or direction of any treatment comparison.

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

Analysis population for the primary outcome, as defined in the registry: Imaging data were not extracted to protect confidentiality of participants.

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 Post-Ketamine Rs-fMRI Data, measured over 24 hours.

The primary outcome is titled Post-Ketamine Rs-fMRI Data. Its timeframe is 24 hours, and its description specifies fMRI data 24 hours post infusion. Resting-state functional MRI measures patterns of coordinated brain activity while a participant is not performing a specified task. The brief summary refers to global brain connectivity, or GBC, and anticipates an increase in fronto-temporal cortex after ketamine. The record does not provide a unit, parameter, or numerical definition for the primary measure.

In general, connectivity measures are used to describe statistical relationships among signals from different brain regions. They can help characterize patterns of activity across a network, but the measure depends on the acquisition and analysis choices. Without the imaging values, measurement definition and analysis details, readers cannot assess the size, variability, direction or precision of the primary outcome in this study.

The endpoint is relevant to the stated research purpose because the summary focuses on characterizing ketamine-associated patterns in resting-state imaging. Relevance to the research question does not itself establish a result. The registry states that imaging data were not extracted to protect confidentiality of participants. Consequently, the primary outcome is not available for numerical interpretation in the registry record, and no conclusion about the anticipated connectivity pattern can be drawn from the posted primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, double-masked, parallel phase 1 study, with Ketamine Plus Lamotrigine and Ketamine Plus Placebo as the named arms. These design descriptors provide context for interpreting a planned comparison, but the record does not include the primary outcome values or a reported analysis. The statistical concepts below are general explanations; they do not describe an analysis confirmed to have been conducted for this trial.

What does randomization contribute?

In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to limit systematic differences between groups at assignment, including differences that investigators may not have measured. Randomization does not guarantee that groups will be similar in every characteristic, particularly in a study with very small enrollment. The registry labels this study randomized but does not describe the sequence generation, concealment or implementation. Those details are not reported in the registry record, so the quality of the randomization procedure cannot be assessed from the record.

What does masking mean?

In general, masking means that some people involved in a study do not know which treatment a participant receives. It can reduce the chance that expectations influence participant reports, clinical management or outcome assessment. The registry labels the study double-masked, but does not specify who was masked or how masking was maintained. The primary endpoint is imaging data, and the record does not explain whether image acquisition, processing or analysis personnel were masked to assignment. It is therefore possible to describe the registered design label, but not to evaluate the practical success of masking.

How should an endpoint estimate be read?

In general, an endpoint estimate should be read together with its definition, the population included, the comparison being made and a measure of uncertainty. For a continuous imaging measure, an analysis might report a group-level summary or a contrast between groups. The precise form depends on the measurement and analysis plan. The registry does not supply the parameter, unit or numerical endpoint result for Post-Ketamine Rs-fMRI Data. It also does not report a primary analysis or analysis population. No effect estimate or uncertainty measure can therefore be explained for this outcome.

What does a confidence interval communicate?

In general, a confidence interval gives a range of estimates compatible with the observed data under a statistical procedure and its assumptions. A narrow interval indicates greater precision than a broad interval, while the interval's location communicates which effect sizes remain compatible with the data. It does not resolve bias, measurement problems or limitations in study conduct. Since the registry record gives no primary estimate or interval, the precision of any imaging finding cannot be assessed. The small enrollment recorded for the study is also important context: estimates from very small studies are generally vulnerable to substantial uncertainty, but no numerical uncertainty measure is available.

What are the planning assumptions?

The registry describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial had a particular power or that a treatment effect was observed. The record does not report the numerical illustration values or a numerical observed effect in the available outcome information. The planning description therefore cannot establish an adequate sample size or the precision of the study results.

In general, sample-size calculations depend on assumptions about the target effect, variability, allocation and analysis. A planning calculation asks what sample size might be needed under those assumptions. It does not report what happened in a completed or terminated study. A calculation based on a trial's observed effect can also be unstable when the underlying estimate is imprecise. Any planning illustration should be kept conceptually separate from observed enrollment and outcome results. The registry's stated assumptions do not constitute a reported sample-size justification for this study; a protocol-based justification is not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too small, making results appear more precise than warranted. The choice of model should reflect the outcome's distribution and the design. The registry does not report the outcome distribution, model, dispersion estimate or analysis method for the imaging endpoint. Over-dispersion is therefore a general statistical consideration, not a reported issue or finding in this study.

Time-to-event methods are not described for the primary imaging endpoint. The registry record does not report an analysis method for this endpoint, and no particular model or testing procedure should be assumed. In general, a statistical method should be selected in advance or justified by the data structure and research question. The available record is insufficient to determine what method, if any, was applied to the imaging data.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 0 analyses. It does not provide the complete outcome definitions, numerical results for the secondary outcome, or a statistical analysis plan. The primary outcome is described as fMRI data at 24 hours post infusion, but the record does not give a numerical primary result. Imaging data were not extracted to protect confidentiality. The registry also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Thus, the primary outcome cannot be represented as a single comparison from the information in the record.

In general, multiplicity arises when researchers examine several outcomes, time points, groups or statistical contrasts. If many tests are considered, the chance of finding a nominally notable result by chance can increase. Methods to address this may include defining a primary comparison in advance or adjusting inference across tests. Whether adjustment is needed and which method is appropriate depend on the analysis plan. The registry record does not report an adjustment strategy, a hierarchy among outcomes, or an interim-analysis plan. None should be inferred.

The registry does not report an analysis population, such as which participants were included in the primary analysis or how exclusions were handled. It also does not provide participant-level imaging completeness or a missing-data method. The stated confidentiality reason explains why imaging data were not extracted, but does not describe whether imaging was collected for all participants or how missing observations, if any, were addressed in the study analysis. These details are not reported in the registry record.

In general, missing outcome data can affect interpretation if the availability of measurements is related to participant characteristics or outcomes. Methods for handling missingness rely on assumptions, and those assumptions should be made transparent. Without details on data availability and analysis populations, readers cannot assess whether the posted outcome information represents all randomized participants. The registry's absence of extracted imaging results prevents evaluation of the endpoint regardless of the method that may have been used.

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 serious adverse-event counts separately for the two named groups. In Ketamine Plus Lamotrigine, 2 participants were at risk and 0 were affected by a serious adverse event. In Ketamine Plus Placebo, 1 participant was at risk and 0 were affected. The registry reports 0 deaths in each group. For other adverse events, it reports 0 affected among 2 at risk in Ketamine Plus Lamotrigine and 0 affected among 1 at risk in Ketamine Plus Placebo. No top serious adverse-event terms are listed.

These are descriptive counts, not comparative safety estimates. The small reported at-risk groups mean that the absence of a recorded event should not be read as establishing that events cannot occur. The registry does not provide event definitions, collection procedures, exposure duration, severity details for non-serious events, or additional safety analyses. It also does not report whether the counts cover the same observation period for all participants. These details are not reported in the registry record.

In general, adverse-event counts describe events recorded during study participation; they do not by themselves establish that a treatment caused or prevented an event. The counts should be read as the registry's reported observations, not as a basis for clinical advice or a broad safety conclusion. They are distinct from the primary imaging outcome, whose data were not extracted.

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

The registry record establishes that a small phase 1 randomized, double-masked, parallel study was conducted under the title The Sustained Effects of Ketamine. Its stated purpose was to characterize effects of a single, sub-anesthetic ketamine dose in resting-state fMRI among healthy subjects. The two named arms were Ketamine Plus Lamotrigine and Ketamine Plus Placebo. Enrollment was 3, and the study status is TERMINATED.

The record does not establish whether the expected increase in global brain connectivity in fronto-temporal cortex occurred. That pattern appears in the brief summary as an anticipated result, while the primary imaging data were not extracted to protect participant confidentiality. No numerical primary outcome, treatment contrast, confidence interval or p-value is reported. A reader therefore cannot determine the direction or magnitude of an observed imaging effect, or how precisely it was estimated.

The registry's safety counts report no serious adverse events, other adverse events or deaths in the listed at-risk groups. Those descriptive counts do not answer the primary imaging question, and the available record does not support a broad comparison of safety between groups. Likewise, the termination status does not reveal why the study ended. Its reason is not reported in the registry record.

In general, a study's purpose and design describe what researchers sought to investigate and how they planned to organize the comparison. They are not substitutes for outcome data. Even when a study reports an estimate, its interpretation depends on the endpoint definition, analysis, uncertainty and potential limitations. In this case, the available registry information is useful for identifying the question and design, but does not allow a conclusion about the primary outcome. It also cannot establish effects beyond the population and conditions actually studied, which are not fully characterized in the record.

13. Why This Trial Matters Statistically

This study is statistically notable as an example of the difference between a registered research question and an interpretable result. The registry states a specific imaging aim and names an expected pattern of increased global brain connectivity in fronto-temporal cortex. Yet the primary imaging data were not extracted, and no numerical primary outcome analysis is reported. Without an estimate and its uncertainty, the research question cannot be answered from the posted registry information.

The record also illustrates why design labels and outcome evidence must be read separately. Randomization, double masking and a parallel structure describe intended design features. They do not show whether groups were balanced, whether masking was maintained, or whether the primary endpoint differed between groups. Those questions require study details and outcome analyses that are not reported in the registry record.

Enrollment of 3 makes the distinction between a planning calculation and observed evidence especially important. A sample-size illustration is a planning exercise based on assumptions; it is not observed power and does not replace an analysis of the endpoint. The registry's planning description names assumptions, but the registry entries do not give a numerical observed effect or numerical planning result. The reason for termination is also not reported, so it cannot be used to explain the enrollment or outcome record.

Finally, the safety counts are reported but cannot stand in for the unavailable imaging results. Clear separation of study purpose, planned design, recorded events and analyzed outcomes helps prevent claims that go beyond the information available. This record makes those distinctions essential: it documents an imaging question and limited safety counts, while leaving the primary statistical result unavailable.

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 primary limitation for interpretation is the absence of extracted imaging data. The registry explicitly says these data were not extracted to protect confidentiality of participants. It provides no numerical primary endpoint result, parameter, unit, effect estimate or uncertainty measure. The study's stated expectation about connectivity must therefore remain distinct from an observed finding.

The record reports enrollment of 3 but does not explain how that enrollment compares with the intended enrollment or any recruitment target. It does not report a protocol-based sample-size justification. The listed planning assumptions do not resolve that gap and do not establish the achieved precision of the study. The registry also lists 0 analyses, leaving the statistical approach and analysis populations unreported.

Some design and population details are missing. The registry names a randomized, double-masked, parallel design and two arms but does not explain randomization or masking procedures, treatment details, dose amount, eligibility criteria or participant characteristics. The condition is listed as Mental Disorders, whereas the brief summary describes healthy subjects; the record does not reconcile these descriptions.

The study is marked TERMINATED, but the reason is not reported in the registry record. The record does not provide a detailed account of follow-up, imaging-data completeness, missing-data handling, outcome categories or time points, or multiplicity procedures. Safety counts are also limited to the reported at-risk and affected counts, with no top serious adverse-event terms listed. These gaps restrict evaluation of study conduct, analysis choices and the scope of any conclusions that might otherwise be drawn.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Sustained Effects of Ketamine — NCT02708849.
• Registry record last updated 2020-07-02; status last verified 2020-06.
• Results first posted 2020-07-02.
• 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

NCT02708849, The Sustained Effects of Ketamine, is listed as a phase 1 randomized, double-masked, parallel study sponsored by Yale University. The named arms are Ketamine Plus Lamotrigine and Ketamine Plus Placebo. Enrollment was 3, the study start is recorded as 2015-06, primary completion as 2020-03, and status as TERMINATED.

The primary outcome is Post-Ketamine Rs-fMRI Data at 24 hours post infusion. The brief summary describes healthy subjects and anticipates increased global brain connectivity in fronto-temporal cortex. Imaging data were not extracted to protect confidentiality, so no numerical primary result is reported in the registry record. The record lists 2 outcome measures and 0 analyses.

Reported safety counts show 0 serious adverse events, 0 other adverse events and 0 deaths in the named groups. The reason for termination, detailed analysis methods, and numerical primary outcome results are not reported in the registry record.