Pattern Separation, Brain Derived Neurotrophic Factors, and Mechanisms of Vortioxetine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pattern Separation, Brain Derived Neurotrophic Factors, and Mechanisms of Vortioxetine (NCT02969876), a na phase 4 study. The primary outcome is Quick Inventory of Depressive Symptomatology - Clinician Version (QIDS-C).

2. Clinical Question

Statistically, the central question is whether a six-week course of open-label vortioxetine was accompanied by a change in clinician-rated symptom scores in the enrolled participants. A single-group study can describe measurements over time if those measurements and their analysis are reported. Without a concurrent comparator, however, any observed change cannot by itself separate a treatment effect from other explanations, such as the passage of time, clinical contact, or measurement variation. The registry record does not report the outcome values or an analysis addressing change. The question is therefore identifiable from the study description, but its numerical answer is not reported in the registry record.

3. Trial Design

This is a phase 4, single-group, open-label study of vortioxetine. The registry lists allocation as not applicable and masking as none. These features mean the record does not describe randomized assignment or blinding. It lists one study arm, called “Study Phase,” in which participants received open-label vortioxetine for six weeks. The arm description says participants attended weekly visits, met with clinicians, and completed cognitive tasks.

The brief summary calls the study a six-week proof-of-concept trial for 20 patients with major depressive disorder, while the registry enrollment field lists 2. Those figures describe different entries in the record: the summary’s intended group size and the enrollment listing. The record does not explain the difference, so it should not be interpreted as evidence about why enrollment was lower or whether the study stopped early for a particular reason. The status is terminated. The start date is 2017-08-24, and primary completion is listed as 2018-08-06.

The primary outcome is a continuous score, summarized in the registry’s outcome definition as a mean with standard deviation, at six weeks. Two secondary outcomes are named: the Digital Symbol Substitution Test and the Rey Auditory Verbal Learning Test. The record lists 3 outcome measures and 0 analyses. It does not report the outcome values, analysis population, or a statistical analysis plan. The reason for termination and any protocol details beyond those stated are not reported in the registry record.

Because there is no concurrent control group, the design supports description of the observed participants and measurements, but not a randomized treatment contrast. The open-label design also means participants and clinicians were not masked to treatment, according to the registry. Those design features are important when interpreting any within-group change, but the record does not provide results from which to estimate such a change.

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 Quick Inventory of Depressive Symptomatology - Clinician Version (QIDS-C), measured over 6 weeks.

The primary endpoint is the Quick Inventory of Depressive Symptomatology - Clinician Version (QIDS-C), recorded as a score on a scale at six weeks. The registry describes it as a measure of depressive symptom severity. Scores range from a minimum of 0 to a maximum of 27, and a higher score means a worse outcome.

A clinician-rated symptom scale can provide a structured way to quantify symptom severity. Treating the score as a continuous measure allows investigators to summarize a group with a mean and standard deviation, as specified in the registry. The mean describes the group’s average score, while the standard deviation describes the spread of scores around that average. These summaries can help characterize measurements, but they do not on their own establish whether a treatment caused a change.

The stated timeframe is six weeks. The record does not report a baseline score, a six-week mean, a change score, a standard deviation, or an estimate of uncertainty for the primary outcome. It also does not specify in the posted outcome description whether the six-week value is intended to be compared with baseline or interpreted in another way. Thus, the endpoint’s purpose and scale are described, but the observed primary result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. General statistical explanation: a mean condenses the measurements into an average, while a standard deviation describes how dispersed individual measurements are around that average. Neither summary reveals the full distribution, and neither alone describes uncertainty in the estimated mean. The record does not report these numerical summaries for the QIDS-C outcome.

What a single-group design can estimate

In a single-group study, the observed participants receive the intervention without a concurrent comparison arm. If measurements are taken before and after treatment, an analysis may describe within-person change or compare group averages across time. The registry does not report baseline results or a change analysis, so it is not possible to tell which approach, if any, was used. More generally, a within-group change is not equivalent to a randomized treatment effect: without a control group, changes that would have occurred in the absence of treatment cannot be directly observed.

Allocation is listed as not applicable, and the model is single-group. There is no like-for-like control comparison. Masking is listed as none, consistent with the description of open-label treatment. General statistical explanation: knowledge of treatment assignment can influence expectations, reporting, clinician ratings, or assessment behavior. This does not prove that such influences affected this study, but it is a consideration when interpreting open-label outcomes.

Precision and uncertainty

A point estimate, such as a mean or mean change, would describe the estimated outcome in the analyzed participants. A confidence interval would show the range of values compatible with that estimate under the statistical model and its assumptions. A narrow interval generally indicates greater precision than a wide interval, but precision is distinct from whether a result is clinically meaningful or causally attributable to treatment. No primary outcome estimate or confidence interval is reported in the registry record.

The listed enrollment is 2. With such a limited number of recorded participants, estimates would generally be sensitive to each participant’s measurements; this is a general property of small samples, not a claim about unreported values from this study. The registry does not report the number included in a primary analysis, whether all enrolled participants contributed outcome data, or how any incomplete measurements were handled.

Planning illustrations and observed power

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 two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These assumptions describe a hypothetical planning exercise, not the single-group trial’s actual design. The numerical planning results and the observed effect used for that exercise are not reported in the registry record.

Such sample-size figures, when presented, are planning illustrations: they indicate participant numbers under specified assumptions rather than the number needed to make the current result true. They are not “observed power,” and they do not remedy the absence of an outcome estimate or a control group. General statistical explanation: power calculations depend on the assumed effect, variability, significance level, allocation, and analysis model. If those assumptions do not match a future study, the resulting planning numbers may not transfer directly.

Over-dispersion and model choice

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. In settings where it applies, ignoring over-dispersion can make uncertainty appear too small. The listed primary endpoint is a continuous score analyzed as a mean with standard deviation, and the record does not identify an over-dispersion model or report a statistical analysis plan. It is therefore not possible to assess model choice or whether any particular adjustment was used.

The registry lists 0 analyses. No test statistic, p-value, confidence interval, or model-based estimate is reported for the primary endpoint. The method description establishes how the outcome is defined, but not how it was ultimately analyzed. The statistical analysis plan, any interim analyses, and any sample-size justification are not reported in 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("Study Phase")
n   <- c(2)
m   <- c(12.5)
sp  <- c(10.6)
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  Study Phase  2  12.500  10.600  -82.737  107.737

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary QIDS-C outcome and two secondary outcomes: the Digital Symbol Substitution Test and the Rey Auditory Verbal Learning Test. It also lists 3 outcome measures and 0 analyses. The multiplicity strategy—how the analysis would account for examining more than one outcome or comparison—is not reported in the registry record. Without that information and without reported analyses, the risk of selectively emphasizing one result among several cannot be assessed.

Missing-data methods are not reported in the registry record. The record does not say whether any measurements were missing, how missing outcomes were handled, or whether an analysis used all enrolled participants or a subset. The participant analysis population and inclusion criteria for the outcome analysis are also not reported. These omissions matter because the number and characteristics of participants contributing measurements can affect the interpretation of a mean or change estimate.

The registry lists enrollment of 2, but that alone does not establish how many contributed primary outcome data at six weeks. No baseline or follow-up values are reported. Any imputation method, sensitivity analysis, or other assessment of missing data is not reported in the registry record.

Likewise, the statistical analysis plan and any interim analyses are not reported in the registry record. With no outcome analyses posted, there is no basis for evaluating adjustments for multiplicity, robustness to missingness, or whether the final analysis followed a prespecified plan.

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 non-serious adverse event terms

The registry’s adverse-event entries list 2 participants at risk for serious adverse events and 0 affected by serious adverse events. It lists 2 participants at risk for other adverse events and 1 affected. The number of deaths is 0. No top serious adverse-event terms are listed.

These are counts within the registry’s listed group, “Open Trial Vortioxetine.” They do not provide a comparison with an untreated or alternative-treatment group, so they cannot establish whether an event rate was caused by treatment or differs from another option. The record does not report event descriptions for the other adverse event, its severity, timing, or relationship to treatment. It also does not provide further detail on how events were collected or classified.

With enrollment listed as 2, the safety counts describe a very limited group. General statistical explanation: counts from a small group provide little precision about how often events might occur in a broader population. A count of 0 serious events in this group does not demonstrate that serious events cannot occur. These figures should be read as the registry’s recorded counts, not as a comprehensive estimate of safety.

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

The registry record shows that a phase 4, open-label, single-group study of vortioxetine was terminated and lists enrollment of 2. It identifies the QIDS-C at six weeks as the primary outcome and describes two cognitive secondary outcomes. It does not report numerical results or analyses for those outcomes. As a result, the posted information does not show whether symptom scores or cognitive measures changed, in which direction they changed, or how precise any estimate might be.

The design also limits causal interpretation. There was no concurrent control group, and treatment was open-label. Even if within-group results were available, they would describe changes among the observed participants and would not, by themselves, establish that vortioxetine caused those changes. A controlled comparison would be needed to distinguish a treatment-associated effect from other explanations more convincingly.

The registry’s brief summary describes an intended group of 20, while the enrollment field lists 2. The record does not explain this difference or the reason for termination. It would therefore be inappropriate to infer the cause of the enrollment figure or termination from the entries alone.

The adverse-event entries record 0 serious adverse events among 2 participants at risk, 1 other adverse event among 2 at risk, and 0 deaths. Those counts are descriptive and do not provide a comparative safety estimate. They also should not be taken as evidence that no uncommon or unrecorded events could occur.

In short, the record describes a study and its intended measurements, but it does not provide the outcome evidence needed to estimate a treatment-associated change. It neither establishes benefit nor establishes lack of benefit. The absence of reported results is a limitation of what can be concluded from this registry record, not a result showing no effect.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design and registry entries sharply delimit what can be learned from the posted information. It is a single-group, open-label study with enrollment listed as 2, yet the brief summary describes a proof-of-concept study intended for 20 patients. The record marks the study terminated and lists 0 analyses. These details make it especially important to distinguish the study’s stated question from an answer supported by reported outcome data.

The primary endpoint is defined clearly enough to identify its scale and direction: the QIDS-C measures depressive symptom severity, and higher scores mean worse outcomes. But an outcome definition is not an outcome result. Without reported scores, changes, variability, or uncertainty, readers cannot judge the magnitude or precision of any observed pattern. This distinction is central to statistical literacy: a well-described endpoint does not itself establish a finding.

The single-group design also illustrates the difference between describing change and estimating a causal effect. A before-and-after comparison, if reported, could characterize participants’ measurements over time. Without a control group, it would not isolate what would have happened without the intervention. Open-label treatment adds another consideration because participants and clinicians were not masked, as listed in the registry.

The registry’s planning assumptions describe a hypothetical sample-size exercise involving equal allocation between two arms and a normal approximation. Those assumptions do not match the listed single-group design, and the planning exercise cannot supply missing outcome evidence. It is useful to keep planning quantities separate from observed results: planning illustrations address hypothetical future designs, while the trial’s own reported results would describe what was measured in its participants.

For readers, the key statistical lesson is to separate endpoint definition, study design, enrollment, analysis, and result. Here, the record documents the first several elements but does not provide an evaluable primary result. That makes restrained interpretation essential.

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 primary limitation for interpreting this record is that numerical outcome results and analyses are not reported. The registry names the QIDS-C as the primary endpoint at six weeks, but provides no baseline or follow-up score, change estimate, standard deviation, confidence interval, or test result. The named secondary outcomes likewise have no reported numerical results or analyses.

The study has no concurrent control group and is open-label. Therefore, even if within-group changes were available, they could not by themselves establish a causal treatment effect. The lack of masking also leaves possible expectation or assessment influences unaddressed in the registry description.

Enrollment is listed as 2, whereas the brief summary describes a study for 20 patients. The registry does not explain the difference. It also lists the study status as terminated without reporting the reason. These entries limit assessment of the study’s conduct and the context for its recorded enrollment, but do not establish why the difference or termination occurred.

The record does not report participant characteristics, eligibility details, dose, dosing schedule, analysis population, missing-data handling, multiplicity strategy, statistical analysis plan, interim analyses, or sample-size justification. The listed safety counts are limited to the recorded group and are not comparative; details of the other adverse event are not given. Together, these gaps prevent assessment of outcome precision, robustness, and generalizability from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pattern Separation, Brain Derived Neurotrophic Factors, and Mechanisms of Vortioxetine — NCT02969876.
• Registry record last updated 2019-10-14; status last verified 2019-09.
• Results first posted 2019-10-14.
• 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 4 study of vortioxetine is listed as a terminated, open-label, single-group trial with enrollment of 2. The brief summary describes a six-week proof-of-concept study intended for 20 patients with major depressive disorder. Participants were described as attending weekly visits and completing cognitive tasks.

The primary outcome was the QIDS-C score at six weeks; the registry describes higher scores as indicating worse symptom severity. Secondary outcomes named were the Digital Symbol Substitution Test and Rey Auditory Verbal Learning Test. The record lists 3 outcome measures and 0 analyses.

No numerical primary or secondary outcome results are reported in the registry record. The reason for termination, analysis methods, missing-data handling, and sample-size justification are also not reported. Safety entries list 0 serious adverse events among 2 at risk, 1 other adverse event among 2 at risk, and 0 deaths.