miRNAs, Suicide, and Ketamine - Plasma Exosomal microRNAs as Novel Biomarkers for Suicidality and Treatment Outcome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for miRNAs, Suicide, and Ketamine - Plasma Exosomal microRNAs as Novel Biomarkers for Suicidality and Treatment Outcome (NCT02418195), a non-randomized phase 2 study. The primary outcome is Beck Scale for Suicide Ideation (BSS).

2. Clinical Question

The central scientific questions concern both biological associations and changes following infusion. One question is whether miRNA expression varies across groups defined by suicide attempt and ideation history. Another is whether changes in miRNAs after ketamine are associated with changes in suicidal or depressive symptoms. The study description also identifies questions about links between miRNA and mRNA regulation, but final answers to those questions are not reported in the registry record.

These questions involve distinct kinds of evidence. Differences among groups can describe associations between clinical history and measured biomarkers, but the non-randomized design does not isolate the effect of group membership. Repeated blood collection in the MDD groups can track measurements across time, but the registry record does not include results for those measurements. The primary clinical measure is reported at one post-dose time point; that alone would not answer every biomarker or time-course question in the study description.

3. Trial Design

This was a Phase 2, non-randomized, unmasked, parallel-group study. The registry lists enrollment of 247 and status as completed. It identifies major depressive disorder as the condition under study and the University of Alabama at Birmingham as the sponsor. The study began on 2015-04-20, and its primary completion date is listed as 2020-12-30.

The study included three MDD groups defined by recent suicide attempt and suicidal ideation history, alongside healthy controls. Participants with MDD received a one-time intravenous ketamine infusion at 0.5 mg/kg. The brief description specifies blood draws before infusion and at 30 minutes, 180 minutes, 24 hours, and 14 days post-infusion. Healthy controls had a one-time blood draw to examine miRNAs, rather than the ketamine infusion and repeated sampling described for the MDD groups.

Because allocation was non-randomized, group membership was determined by clinical status rather than random assignment. The groups also differed in whether they received ketamine and in the sampling procedures described. They are not interchangeable treatment arms, so a simple comparison between them cannot be interpreted as the causal effect of ketamine. The registry record does not report an adjusted analysis or other method that would address differences among groups.

The registry describes several symptom and safety measures in addition to the primary Beck Scale for Suicide Ideation outcome. These include depression, anxiety, hopelessness, psychiatric symptoms, dissociative symptoms, mania, and treatment-emergent events. Although the study status is completed, the registry record contains no posted statistical analyses for these outcomes. The record’s narrative says that data collection was complete and primary and secondary outcome results were complete as of July 2022, while final analysis of mRNA samples was still being worked on. It does not report the final numerical results.

The record notes that participant numbers associated with the primary outcome correspond to usable laboratory samples and that this is the reason for a discrepancy in numbers. The actual group-specific usable-sample counts are not reported in the registry record. The protocol details, including a full statistical analysis plan and the rationale for the planned enrollment, are also not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A number of participants were excluded for not meeting inclusion or meeting exclusion criteria, in total 51. These were considered screen failures.

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 Beck Scale for Suicide Ideation (BSS), measured over 180 minutes post dose.

The registry lists the primary outcome as the Beck Scale for Suicide Ideation (BSS), measured at 180 minutes post dose. The outcome description calls the instrument the Beck Scale for Suicidal Ideation (BSSI). It is described as a 21-item self-report scale measuring the current intensity of specific attitudes, behaviors, and plans related to suicide. Each item has three response options graded from 0 to 2, and the stated total score ranges from 0-42. Higher scores indicate more severe symptoms.

The endpoint is a continuous measure, and the registry identifies the planned summary as a mean with standard deviation. A mean can describe the average score in a group, while the standard deviation describes how dispersed individual scores are around that average. These summaries do not show the full score distribution or establish that a difference between groups is caused by an intervention.

In general, a scale focused on suicidal ideation can provide a structured way to describe symptom intensity at a specified assessment time. The 180-minute assessment is the primary time point listed in the record; it should not be confused with the other blood-draw times or with longer-term outcomes. The registry record does not report the group means, standard deviations, participant counts for the endpoint, or a comparison estimate at this time point, so the size and precision of any observed difference cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary measure as a continuous score summarized by a mean and standard deviation. It does not report the statistical tests, models, covariate adjustments, or analysis populations used for the study. The explanations below describe general statistical concepts relevant to this kind of design; they are not claims about analyses that were conducted in this trial.

What does a mean and standard deviation describe?

In general, the mean is the arithmetic average of observed scores in a group. It gives a compact description of the group’s location on the measurement scale. The standard deviation describes how spread out scores are around the mean: a larger standard deviation indicates more variability among individual observations. These two summaries can make a continuous endpoint easier to describe, but they do not reveal every feature of the distribution. They also do not provide the uncertainty around a group mean or a difference between groups unless additional quantities, such as a standard error or confidence interval, are reported.

For the BSS outcome, the registry’s stated score range is 0-42, with higher scores indicating more severe symptoms. A mean score should be interpreted in relation to that scale and to the group and assessment time from which it was calculated. The registry record does not post the means or standard deviations, so the endpoint’s observed level and variability cannot be described from the record.

What would a comparison estimate mean?

In general, a comparison estimate expresses the size and direction of a difference between groups or assessment times. Its interpretation depends on the contrast being estimated: for example, a difference between two clinical-history groups is not the same question as change within a group after infusion. A confidence interval communicates uncertainty around an estimate under the analysis model. A narrow interval indicates greater precision than a wide interval, although precision alone does not establish that an effect is important.

The record does not post an estimate or confidence interval for the primary outcome. It also does not specify whether the primary analysis was intended to compare groups, assess change from baseline, or use another contrast. The endpoint and time point are identified, but the complete statistical question and analysis model are not reported in the registry record.

Why does the non-randomized design matter?

In general, random assignment helps balance measured and unmeasured participant characteristics between treatment groups, on average. Without random assignment, groups may differ in ways related both to group membership and to the outcome. Here, the groups were formed according to MDD and suicide-history criteria, and the healthy control procedure differed from the MDD procedures. Consequently, a raw group contrast would be descriptive unless the design and analysis supported a stronger interpretation. The registry record does not identify a causal-inference strategy or adjustment model.

Parallel groups mean that different participants belong to the different groups rather than every participant being assigned to each group. Repeated blood sampling after infusion in the MDD groups may produce correlated observations within each participant. In general, analysis of repeated measurements needs to account for that dependence; treating each measurement as independent can misstate uncertainty. The registry record does not report how repeated measurements were modeled or whether the primary clinical outcome was analyzed together with the biomarker data.

What is over-dispersion, and is it relevant?

In general, over-dispersion means that observed variability is greater than a chosen statistical model expects. It is especially a concern for outcomes such as counts when a model assumes a particular relationship between the mean and variance. The listed primary endpoint is a bounded continuous score, not a count, and the registry record does not report an over-dispersion analysis. It would therefore be inappropriate to claim that over-dispersion was present or handled in this study. More generally, the model’s assumptions should be assessed using the outcome type and analysis actually used.

How should planning calculations be read?

In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, significance threshold, allocation, and analysis method. It is not an outcome, and it does not indicate the probability that the study’s conclusion is correct. A calculation based on an observed effect is a retrospective planning illustration, not observed power. The registry record does not report the trial’s own sample-size justification, so any justification or design rationale beyond the stated enrollment is not reported in the registry record.

The record’s stated assumptions for planning illustrations include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. Those assumptions describe an illustration, not the randomized design of this trial: allocation was non-randomized, and the clinical groups were not like-for-like arms. The record does not provide numerical outputs for such calculations in the registry record described for this analysis, so no participant requirement should be inferred from these assumptions.

What can be concluded from the posted analysis information?

The registry reports no statistical analyses and does not post numerical outcome estimates. This means the design and measurement plan can be described, but observed effect sizes, uncertainty, and statistical significance cannot be explained. General statistical concepts clarify what those quantities would mean; they do not fill in results that are absent from the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("MDD With Recent Suicide Attempt", "MDD With Suicidal Ideation no Attempt", "MDD Without Suicidal Ideation no Attempt")
n   <- c(56, 56, 60)
m   <- c(9.09, 8.46, 1.9)
sp  <- c(9.843, 8.954, 3.551)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  MDD With Recent Suicide Attempt  56  9.090  9.843  6.454  11.726
CARM  MDD With Suicidal Ideation no Attempt  56  8.460  8.954  6.062  10.858
CARM  MDD Without Suicidal Ideation no Attempt  60  1.900  3.551  0.983  2.817

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary BSS outcome at 180 minutes post dose and lists secondary measures covering depression, anxiety, hopelessness, psychiatric symptoms, dissociation, mania, and treatment-emergent events. It also describes biomarker questions involving miRNA expression and response to ketamine. The record identifies nine outcome measures, but it does not report a multiplicity strategy, such as a hierarchy of tests, adjustment procedure, or distinction between confirmatory and exploratory analyses. The statistical analysis plan is not reported in the registry record.

In general, testing many outcomes or time points can increase the chance of finding at least one apparently unusual result by chance. Multiplicity procedures can control or contextualize that risk, but the choice depends on the intended family of questions and analysis plan. Since no statistical analyses or multiplicity approach are posted, the record does not permit assessment of how multiple outcomes or repeated time points were handled. The number of outcomes alone does not establish that a particular adjustment was or was not used.

Missing-data handling is also not reported. The primary outcome description says participant numbers correspond to usable laboratory samples and notes that this explains a discrepancy in numbers. However, the record does not report the actual endpoint-specific counts, reasons for missing observations, or methods used to handle missingness. In general, missingness can affect both precision and the interpretation of estimates, especially if the chance of an observed measurement is related to participant characteristics or outcome values.

The analysis populations are not described in enough detail to determine who was included in each result. The registry record does not state whether analyses used all enrolled participants, only participants with available measurements, or another defined population. Given the absence of posted analyses and participant-level accounting, neither the impact of missing data nor the degree to which results represent the enrolled groups can be evaluated.

12. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: elevated blood pressure (1.6%), worsening depression and si (1.6%), suicide attempt (1.6%), altered mental status (1.6%), acute worsening depression (1.6%).

The registry reports serious adverse event counts by group. For MDD with a recent suicide attempt, 62 participants were listed at risk and 5 were reported as having a serious adverse event. For MDD with suicidal ideation and no attempt, 63 were listed at risk and 1 was reported with a serious adverse event. For MDD without suicidal ideation and no attempt, 61 were listed at risk and 1 was reported with a serious adverse event. For healthy controls, 61 were listed at risk and 0 were reported with a serious adverse event. Deaths are listed as 0 in each group.

The record also lists serious-event terms including elevated blood pressure, worsening depression and SI, suicide attempt, altered mental status, acute worsening depression, and hospitalization for worsening depression and anxiety. Each term is listed as 1.6%. The registry does not map these terms to specific groups in the listed terms, so those percentages should not be assigned to a particular group from this information alone.

These counts describe events recorded in the study, not comparative risks established by a randomized safety analysis. The groups were non-randomized and differed by clinical status; the healthy control group also had a different study procedure. The record does not provide a statistical comparison, exposure-adjusted rates, or detailed event timing and attribution in the information. The counts should therefore be read descriptively, without treating differences between groups as evidence that the intervention caused or prevented an event.

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

The registry record establishes that this was a completed, non-randomized study designed to investigate exosomal miRNAs in relation to suicidal ideation or behavior and ketamine response. It identifies the clinical groups, the ketamine infusion for MDD participants, the blood-draw schedule, and the primary BSS assessment at 180 minutes post dose. Those details describe what the study set out to measure, rather than what the measurements showed.

The posted record does not include numerical outcome results or statistical analyses. It therefore does not support a conclusion about the direction or size of BSS changes, the degree of uncertainty around any difference, or whether miRNA expression differed across the groups. It also does not establish whether biomarker changes were associated with clinical response. The study description’s research questions should not be mistaken for demonstrated findings.

Even if group-level results were available, the non-randomized design would require care in interpretation. Groups defined by suicide attempt or ideation history may differ in other respects, and healthy controls were not described as receiving ketamine or undergoing the same repeated blood draws. A simple comparison would not by itself distinguish biological associations from differences in participant characteristics or study procedures. The registry record does not report an adjustment strategy that would resolve those concerns.

In general, statistical uncertainty matters because an estimate is not an exact description of an underlying effect. Confidence intervals and suitable analyses help show how precisely an effect is estimated, while study design affects what causal claims an estimate can support. In this record, those estimates and intervals are absent. Enrollment of 247 and completed status do not substitute for endpoint-specific participant counts or results.

The appropriate reading is narrow: the registry documents a research program and its measures, and it reports some safety counts, but it does not provide the outcome evidence needed to quantify the primary or biomarker findings. Neither a positive nor a null efficacy conclusion can be drawn from the absence of posted results.

14. Why This Trial Matters Statistically

This study is statistically notable because it brings together clinical group comparisons, repeated biomarker measurements, and a clinical scale assessed after infusion. These elements answer different questions. Comparing participants according to suicide-history groups addresses association with clinical status; following measurements over time addresses change after infusion; relating biomarker changes to symptom measures addresses association between biological and clinical response. Those questions require clearly defined contrasts and analyses, which are not reported in the registry record.

The non-randomized design is central to interpretation. The group definitions reflect clinical history, and the control group differs from MDD groups in both diagnosis and described study procedures. Statistical adjustment can sometimes account for measured differences, but it cannot automatically remove unmeasured confounding. The record does not describe the adjustment methods or identify a strategy for causal inference.

There is also an important distinction between a completed study and a publicly interpretable result. The registry says data collection was complete and that primary and secondary outcome results were complete as of July 2022, while noting ongoing final analysis of mRNA samples. Yet no statistical analyses are listed and no numerical primary outcome results are posted in the record. Without estimates, participant counts, and uncertainty measures, readers cannot assess the magnitude or precision of findings.

Finally, the stated discrepancy between participant numbers and usable laboratory samples highlights how biomarker research can depend on sample availability. For sound interpretation, analyses need to make clear which participants contributed to each clinical and laboratory endpoint and how missing samples were handled. Those details are not reported. The design questions and reporting gaps are therefore as important statistically as the listed outcomes themselves.

15. 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 most direct limitation of the registry record for statistical interpretation is that it contains no posted analyses or numerical results for the primary endpoint. Group means, standard deviations, effect estimates, uncertainty intervals, and p-values are not reported. The record’s completed status and narrative statements about completed outcome results do not supply those missing quantities.

The non-randomized allocation limits causal interpretation of group contrasts. MDD participants were categorized by suicide attempt and ideation history, and healthy controls were a separate group with a one-time blood draw. This makes the groups structurally different, and the registry record does not describe an adjustment model or other strategy for addressing confounding. The study design does not support treating the groups as randomized treatment arms.

Endpoint-specific sample counts are not reported. The primary outcome description explains that participant numbers correspond to usable laboratory samples and that this accounts for a discrepancy, but it does not provide the actual counts or describe missing-data methods. Thus, the extent and potential influence of unavailable clinical or laboratory measurements cannot be assessed.

The record does not report a statistical analysis plan, multiplicity handling, model assumptions, analysis populations, or the planned approach to repeated measurements. It also does not provide enough detail to determine how clinical and miRNA findings were linked analytically. These omissions prevent evaluation of whether the statistical methods matched each research question.

Finally, the registry narrative says final analysis of mRNA samples was still being worked on, while also stating that primary and secondary outcome results were complete. The record does not explain the relationship between those stages or give final answers to the stated biomarker questions. Conclusions should therefore remain limited to the design and safety counts actually reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: miRNAs, Suicide, and Ketamine - Plasma Exosomal microRNAs as Novel Biomarkers for Suicidality and Treatment Outcome — NCT02418195.
• Registry record last updated 2022-08-30; status last verified 2022-08.
• Results first posted 2022-07-05.
• 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.

19. Record Summary

This Phase 2 study was non-randomized, unmasked, and parallel-group, with registry enrollment of 247 and completed status. It included MDD groups classified by recent suicide attempt and suicidal ideation, plus healthy controls. The MDD groups received a one-time intravenous ketamine infusion at 0.5 mg/kg; healthy controls had a one-time blood draw.

The listed primary outcome was the Beck Scale for Suicide Ideation at 180 minutes post dose, summarized as a mean and standard deviation. The registry describes a blood-sampling schedule for the MDD groups and names additional clinical and safety measures. It reports serious adverse event counts and no deaths in the listed groups.

The registry record does not report numerical primary outcome results, statistical analyses, group-specific usable laboratory sample counts, or methods for missing data and multiplicity. Consequently, the posted information describes the study and its intended questions but does not quantify the primary clinical or biomarker findings.