Investigation of Genetic Predictors of the Response to Selective Serotonin Re-uptake Inhibitors (SSRI) Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of Genetic Predictors of the Response to Selective Serotonin Re-uptake Inhibitors (SSRI) Treatment (NCT03927950), a na phase 4 study. The primary outcome is Montgomery-Asberg's Depression Rating Scale.

2. Clinical Question

3. Trial Design

This is a Phase 4 study listed as completed, with the University of Tartu as sponsor and an enrollment of 135. Major depression is the recorded condition. The registry describes the design as single group, with no masking and allocation listed as NA. The treatment arm is titled Escitalopram Bupropion Open-label, and its description says No comparator. Escitalopram and bupropion are the listed drug interventions.

These details support describing the record as an open-label, single-group study, not as a randomized controlled comparison. The record does not specify treatment schedules, doses, treatment sequencing, adherence procedures, or whether each participant received both listed drugs. It also does not describe a separate untreated, placebo, or active control group. Consequently, the registered design does not establish a basis for comparing the treatment group with a concurrent control group.

The study title concerns genetic predictors of response to SSRI treatment, while the recorded primary outcome is symptom severity measured with the Montgomery-Asberg Depression Rating Scale. The registry does not identify genetic variants, describe how genetic information was collected or analyzed, or report predictor estimates. The record lists the Hamilton Rating Scale for Depression as a secondary outcome, but does not provide its results.

The registry gives a single primary-outcome time point of 12 weeks. It does not report participant flow, baseline outcome values, the number completing follow-up, or the handling of participants with missing measurements. Although the record is marked completed, that status alone does not establish that all enrolled participants contributed primary-outcome data or that all planned assessments were completed.

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

Reasons for not completing this period:

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 Montgomery-Asberg's Depression Rating Scale, measured over the results are for a single time point (12 weeks).

The primary outcome is the Montgomery-Asberg Depression Rating Scale score, described as a ten-item questionnaire measuring the severity of depressive symptoms. The scale ranges from 0 to 60: the minimum represents lack of depressive symptoms, while the maximum represents severe depressive symptoms. The registry specifies a mean and standard deviation at 12 weeks as the outcome format.

A symptom scale can summarize participants' reported or assessed symptom burden in a numeric form. A mean describes the average score in a group, while the standard deviation describes how dispersed individual scores are around that average. These statistics can characterize the observed group at the stated assessment time, but they do not by themselves establish why scores are at a particular level or whether a treatment caused a change.

The 12-week timing provides the planned assessment point for this outcome. The registry does not report the mean, standard deviation, baseline score, or change from baseline. It also does not report an analysis relating score results to genetic predictors. Therefore, the endpoint's definition and scale range are available, but its observed result and the precision of that result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a continuous score summarized by a mean and standard deviation, assessed at 12 weeks. It does not report the numerical endpoint summaries or the statistical methods used to analyze them. The explanations below describe general statistical concepts; they should not be read as a claim that any particular method was used in this study.

What does a mean describe?

A mean is the arithmetic average of the observed values in an analysis group. For a symptom scale, it can provide a compact description of the group's overall score at a specified time. A mean does not show the full distribution: participants may have scores close to the average, or scores may vary widely around it. The registry supplies the scale's range and intended interpretation, but no observed mean. There is therefore no group average to interpret for the primary outcome.

What does the standard deviation describe?

The standard deviation describes the spread of individual measurements around the mean. A larger standard deviation indicates greater dispersion in the observed scores, while a smaller one indicates that scores are more concentrated. It is not the same as a confidence interval and does not directly quantify uncertainty about the mean. Because the registry does not report the primary-outcome standard deviation, the variability of the 12-week scores cannot be assessed.

What would a confidence interval add?

In general, a confidence interval conveys the statistical uncertainty around an estimate under the chosen model and assumptions. Its width reflects the estimate's precision: narrower intervals indicate greater precision, while wider intervals indicate less. Interpretation depends on the analysis being appropriate for the data and study design. No confidence interval is reported for the primary outcome, and no estimate is reported around which an interval could be interpreted.

What does a p-value answer?

In general, a p-value evaluates how compatible observed data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, nor does it indicate the size or practical importance of an effect. A p-value is meaningful only in the context of the hypothesis, analysis, and assumptions. The registry record does not report a primary-outcome p-value, a tested hypothesis, or a corresponding model.

Why is the single-group design important?

A single-group study can describe outcomes among participants who receive the intervention or interventions as recorded. If scores at different times are measured and analyzed, a within-group change may also be described. Such a change is not the same as a treatment contrast against a control group. Without a concurrent comparator, it is difficult to distinguish treatment-related change from other explanations, including natural change over time, concurrent care, measurement variation, or changes in who remains under observation. The record gives no comparator and does not report a baseline-to-follow-up estimate.

Open-label status means masking is listed as none. In general, lack of masking can affect expectations, care, outcome assessment, or reporting, depending on the measures and procedures. The registry does not describe outcome-assessor masking or procedures intended to reduce these risks. The primary outcome is a symptom rating scale, but the record does not state who completed or rated it.

How should the planning framework be understood?

The record's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with a target effect expressed as a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence about the study's actual design or an analysis performed on its participants. They do not convert this single-group record into a two-arm trial. The planning framework also does not establish observed power. The numerical planning outputs and an observed primary effect are not reported in the registry record, so those illustrations cannot be assessed against study results.

In general, sample-size planning estimates how much information a future study might need under specified assumptions about variability, effect size, allocation, and statistical error rates. If the assumed effect is uncertain, the resulting planning estimate is uncertain too. An illustration based on an observed effect is especially difficult to evaluate when the underlying observed endpoint summary is absent. It should be understood as conditional planning, not as a description of the enrolled sample's actual ability to detect a result.

Why can over-dispersion matter?

Over-dispersion occurs when the data vary more than a statistical model assumes. General models often rely on a specified relationship between the mean and variability. If actual variation is greater than assumed, uncertainty estimates can be too small and tests can appear more decisive than warranted. Analysts may use methods that allow extra variability when appropriate. The registry record does not report a model, a dispersion assessment, or adjustments for over-dispersion. This concept is general and does not imply that over-dispersion was present in this study.

Finally, the record lists zero analyses. This does not identify which procedures may have been performed outside the registry; it means the registry does not report analysis entries from which to assess model choice, adjustment, or inferential results. The distinction is important: outcome definitions and design metadata describe what was registered, while an interpretable statistical result requires the numerical data summary, analysis specification, and uncertainty information.

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("Escitalopram Bupropion Open-label")
n   <- c(135)
m   <- c(9.2)
sp  <- c(10.2)
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  Escitalopram Bupropion Open-label  135  9.200  10.200  7.464  10.936

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, time points, subgroups, or hypotheses are examined. In general, testing many hypotheses can increase the chance of finding an apparently unusual result by chance. Statistical plans may address this through a prespecified primary hypothesis, adjustment procedures, or careful labeling of exploratory analyses. The registry identifies a primary outcome and a secondary outcome, but does not report a multiplicity plan, the hierarchy of analyses, or any adjustment procedure. The number and nature of genetic predictor hypotheses are also not reported.

Missing-data methods are not reported in the registry record. The enrollment is listed as 135, but there is no reported count of participants with a 12-week primary score, no description of withdrawals, and no account of missing measurements. The record does not say whether analyses used observed cases, imputation, or another approach. Without these details, it is not possible to assess whether the analyzed participants differed from those without outcome data or how missing observations may have affected estimates.

Analysis populations are not specified. The registry does not describe an intention-to-treat population, a per-protocol population, or another defined set of participants for endpoint analyses. It also does not report how treatment exposure or protocol deviations were handled. Such choices affect the population to which an estimate applies and can influence the interpretation of results.

These omissions do not establish that multiplicity or missing-data methods were absent from the investigators' work. They mean the relevant plans and results are not reported in the registry record. Since outcome estimates and analysis entries are also not reported, readers cannot evaluate whether the registered outcomes were analyzed as planned or how robust any findings would be to alternative assumptions.

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 lists 135 participants at risk for serious adverse events and 0 affected. It also lists 135 at risk for other adverse events and 9 affected. Deaths are recorded as 0. These are counts in the registry's safety entry, not estimates from a comparative analysis. The record does not identify any specific serious adverse-event terms; the list of top serious terms is empty.

The distinction between serious events and the other adverse-event category matters: the counts are reported separately and should not be combined or treated as interchangeable. The registry does not give further definitions, event timing, severity details, relatedness assessments, or participant-level event narratives. It also does not explain whether the event counts represent participants with events or total events beyond the affected counts shown in the record.

A recorded count of 0 serious events does not demonstrate that serious harm is impossible, and the count of 9 other events does not by itself establish cause. The record has no comparator, so it does not support a relative safety comparison between treatments. These entries should be read as the safety counts recorded for this single-group study, with the limitations of the registry detail in mind.

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

The record establishes that a completed Phase 4 study was registered with an open-label, single-group design and an enrollment of 135. It identifies the Montgomery-Asberg Depression Rating Scale at 12 weeks as the primary outcome and lists escitalopram and bupropion as interventions. It also frames the research topic as genetic predictors of SSRI treatment response. These details describe the study's registered scope, not its findings.

The central primary-outcome result is not reported: there is no 12-week mean or standard deviation, and no baseline or change estimate. No confidence interval, p-value, or other inferential analysis is reported. The record therefore cannot establish the magnitude or precision of symptom scores, whether scores changed over time, or how any change should be interpreted.

The record also does not report genetic predictor results. It contains no estimates linking genetic characteristics to response and no description of how such predictors were tested. The title alone cannot be treated as evidence that a particular genetic marker predicts response or that genetic information improves prediction.

The design does not include a comparator, and no masking is listed. Even if a within-group change were available, it would not by itself isolate a treatment effect. Comparisons against an appropriate control and clear analysis methods would be needed to assess whether observed changes are attributable to treatment rather than other factors. The registry's safety counts likewise do not establish comparative risks.

In general, statistical results describe evidence under an analysis and its assumptions; they do not automatically establish causation or broad applicability. Here, the absence of outcome and analysis results prevents evaluation of effect size, uncertainty, and robustness. The appropriate conclusion is limited: the registry records the study design, outcome definition, and selected safety counts, while the principal efficacy and genetic-prediction findings are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because its title asks a predictive question, while the available registry entries do not include the predictor results needed to answer it. Genetic prediction requires more than identifying a topic or a treatment response measure. Readers would need to know which genetic characteristics were examined, how response was defined, how associations were estimated, and how uncertainty and multiplicity were handled. Those details and findings are not reported in the registry record.

The single-group structure also shapes what can be learned. A group outcome can describe participants, but a treatment effect is inherently comparative: it concerns how outcomes differ under alternative treatment conditions. With no comparator and no reported pre-post estimate, the registry does not provide a direct treatment contrast or a reported change estimate. This distinction helps prevent a descriptive outcome from being mistaken for causal evidence.

The record also illustrates why a named endpoint is not the same as a reported endpoint result. It specifies a recognizable depression severity measure and its assessment time, yet provides no mean, standard deviation, or uncertainty interval. Without these, readers cannot assess magnitude, spread, or precision. Similarly, the safety counts are useful descriptive entries but do not answer comparative safety questions.

Finally, planning assumptions and observed evidence serve different purposes. Planning calculations depend on assumptions and are not evidence that a study detected an effect. The framework recorded for planning uses a hypothetical two-arm allocation, whereas the registered study is single group and has no comparator. Keeping these concepts separate is important when interpreting a planning illustration alongside a registry design.

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 principal limitation for statistical interpretation is that the registry record does not report the numerical primary-outcome results. Although it specifies a mean and standard deviation at 12 weeks, neither is available. No confidence interval, p-value, baseline summary, or change estimate is reported. This prevents assessment of both the observed symptom scores and their precision.

The design is recorded as single group, open label, and without a comparator. It therefore does not support a direct treatment contrast. The record does not report a baseline-to-follow-up analysis either. Treatment details are limited: the listed interventions are escitalopram and bupropion, but dose, schedule, sequencing, and exposure are not described. The arm description says No comparator, so the listed drugs should not be treated as separate randomized arms.

The title concerns genetic predictors, but the registry does not report the genetic characteristics assessed, the predictor analysis, or findings. Details needed to evaluate prediction—such as the response definition, model specification, and uncertainty—are not reported. The record also does not provide participant characteristics that would help judge the study population's representativeness.

Participant flow and missing-data handling are not reported. The analysis population, analysis methods, multiplicity plan, and handling of protocol deviations are also not reported in the registry record. The safety entry gives counts but little detail about event definitions, timing, or relatedness. These gaps limit interpretation without proving that additional analyses or records do not exist outside the registry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Investigation of Genetic Predictors of the Response to Selective Serotonin Re-uptake Inhibitors (SSRI) Treatment — NCT03927950.
• Registry record last updated 2019-04-25; status last verified 2019-04.
• Results first posted 2019-04-25.
• 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.

19. Record Summary

The registry lists NCT03927950 as a completed Phase 4 study sponsored by the University of Tartu, with major depression as the condition and enrollment of 135. Its design is single group, open label, with allocation listed as NA and no comparator. Escitalopram and bupropion are the listed interventions.

The primary outcome is the Montgomery-Asberg Depression Rating Scale mean and standard deviation at 12 weeks. The Hamilton Rating Scale for Depression is listed as a secondary outcome. The record does not report primary or secondary outcome values, genetic predictor analyses, or statistical results. It lists 0 serious adverse events among 135 at risk, 9 other adverse events among 135 at risk, and 0 deaths.