The Effects of Videogames on Depression Symptoms and Brain Dynamics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Videogames on Depression Symptoms and Brain Dynamics (NCT05426265), a randomized na study. The primary outcome is PHQ-9 Total Change From Baseline to Posttreatment: Experimental Group vs. Treatment as Usual Group.

2. Clinical Question

3. Trial Design

The registry describes NCT05426265, “The Effects of Videogames on Depression Symptoms and Brain Dynamics,” as a randomized, quadruple-masked, parallel study. The listed phase is NA. Aalto University is named as sponsor. The record lists an enrollment of 1001 and a status of completed. The recorded start date is 2022-06-28, and the primary completion date is 2024-08-14.

Three interventions or treatment groups appear in the record: MEL-T01, MEL-S01, and treatment as usual. MEL-T01 is a device described as personalized cognitive training delivered through game-based digital-therapeutics software. MEL-S01 is an active comparator described as similar to MEL-T01 but without personalized cognitive training elements. TAU is described as treatment as usual. The record does not give further details about the content of usual care or the delivery schedule for either device.

The primary endpoint compares MEL-T01 with TAU over Day 0 to Day 84. Its analysis population is described as per-protocol completers, restricted to weeks 0–12. The record explains that TAU participants were pooled for this period because they received identical treatment during it, regardless of later allocation. The reported arm estimates are based on 99 MEL-T01 participants and 288 TAU participants; these are the endpoint analysis counts, not the overall enrollment.

The registry also lists MEL-S01 and later TAU group descriptions, but the primary endpoint does not report a MEL-T01 versus MEL-S01 comparison. Details such as the randomization procedure, the people covered by quadruple masking, the treatment schedule, and the protocol’s statistical plan are 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: 1,384 participants were assessed for eligibility and 1,001 were enrolled and randomized to MEL-T01, MEL-S01, or TAU. Participants randomized to TAU were further allocated at baseline to receive either MEL-T01 or MEL-S01 after the initial 12-week period.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Per protocol completer cohort. Analyses were restricted to weeks 0-12; TAU participants were pooled as all received identical treatment during this period, regardless of later allocation.

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.

Population: Per protocol completer cohort.

6. Primary Endpoint

The registry lists the primary outcome as PHQ-9 Total Change From Baseline to Posttreatment: Experimental Group vs. Treatment as Usual Group, measured over Day 0 to Day 84.

The primary endpoint is change in total PHQ-9 score from Day 0 to Day 84, described as the period before and after the 12 week intervention. PHQ-9 is a self-report measure of major depressive disorder that scores each of nine DSM-IV criteria from 0, “not at all,” to 3, “nearly every day.” The total ranges from 0 to 27, and higher scores indicate more severe depression.

A change score expresses how a participant’s score differs between the start and end of the specified period. For this endpoint, a negative change represents a lower posttreatment score than baseline; a more negative group average therefore represents a larger average decrease. The registry reports adjusted least-squares means of -1.941 for MEL-T01 and -0.803 for TAU. The reported adjusted mean difference compares the groups’ changes, rather than comparing their posttreatment scores alone.

PHQ-9 is used as a symptom measure because it provides a numeric summary of self-reported depressive symptoms over the assessed period. Its score direction is essential for reading the result: a reduction in the score is a reduction in the measured symptom severity. The registry record does not state a threshold for judging whether a particular change is clinically meaningful, nor does the primary endpoint by itself describe outcomes beyond the measured period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is identified as a mixed models analysis and reports an adjusted mean difference in PHQ-9 change. The following concepts are general explanations of these methods; the record does not report all modeling details used in this trial.

What does an adjusted mean difference represent?

A mean change summarizes the average difference between baseline and the later assessment within a group. A mean difference between groups then compares those group averages. An adjusted mean difference is an estimate formed with a statistical model that accounts for specified terms or covariates. Adjustment can help estimate a group contrast while accounting for factors included in the model, but the interpretation depends on which factors were included and how they were handled. Those details are not reported in the registry record.

The registry presents least-squares mean changes of -1.941 for MEL-T01 and -0.803 for TAU, and a separate adjusted mean difference of -1.138. The latter is the reported between-group contrast. The individual arm estimates provide context for the direction of the comparison, while the contrast is the statistic directly addressing the primary question. The record labels the estimates as adjusted but does not describe the model’s full specification.

What does the confidence interval convey?

A confidence interval expresses the precision of an estimate under a statistical procedure and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale. The reported 90% confidence interval for the adjusted mean difference is -1.542 to -0.735. Its location gives a range of values compatible with the analysis at that confidence level; it is not a guarantee that the true effect lies within those endpoints, nor does it account automatically for biases or limitations in the analysis.

In general, whether a confidence interval includes zero is relevant when the question concerns a difference: zero represents no difference on the measured scale. Here the reported interval is entirely negative. That statistical feature should be kept separate from clinical importance. The record does not state a threshold for a clinically important difference in PHQ-9 change, so the interval alone cannot establish that the estimated difference is important to patients.

How should the p-value be read?

The reported p-value is < 0.001. In general, a p-value describes how unusual data at least as extreme as those observed would be under a specified null hypothesis and the assumptions of the analysis. It does not give the probability that the null hypothesis is true, the probability that the result occurred by chance in an everyday sense, or the probability that an individual will experience a particular outcome. A small p-value does not remove uncertainty about effect size, analysis choices, missing data, or generalizability.

What is a mixed models analysis?

In general, mixed models can represent both fixed effects, such as group contrasts, and structured variation among observations or participants. They are often used when data have repeated measurements or other forms of dependence. Their results rely on model specification and assumptions about the outcome and the data structure. The registry names mixed models analysis, but does not report the specific model terms, covariance structure, estimation method, or assumptions used for this endpoint. It is therefore not possible to describe those trial-specific choices from the record.

Why does the analysis population matter?

The primary endpoint is based on per-protocol completers, not all 1001 enrolled participants. In general, a per-protocol analysis focuses on participants meeting defined protocol and completion criteria. It can answer a different question from an analysis based on all randomized participants, and selection into a completer cohort may affect how representative the estimate is. The criteria defining this cohort and the number of participants excluded from it are not reported in the registry record.

The endpoint analysis counts are 99 for MEL-T01 and 288 for TAU. These counts indicate the size of the groups used for the posted arm estimates, but they do not explain why the analyzed counts differ or establish the amount or handling of missing outcome data. The record says TAU participants were pooled because their treatment was identical during weeks 0–12, regardless of later allocation. No further details of the pooling procedure are reported.

How do planning illustrations differ from observed power?

In general, a sample-size planning illustration asks how many participants per arm might be needed under specified assumptions about the effect to detect, significance level, allocation, and approximation. Such an illustration is conditional on those assumptions. When based on an observed effect, it should not be interpreted as observed power, nor as evidence that the trial was designed around that effect. The registry record does not report the trial’s sample-size justification or its original design assumptions. Any planning illustration based on the observed contrast is distinct from the trial’s actual enrollment and from the uncertainty in the reported analysis.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a mixed models analysis: an adjusted mean difference of -1.138, with a 90% confidence interval from -1.542 to -0.735 and p < 0.001. That is the analysis to use when describing the sponsor-reported result. The arm estimates are -1.941 for MEL-T01 and -0.803 for TAU, each based on the endpoint analysis cohort.

The registry record does not give a separate recalculated estimate or a recalculated confidence interval for this comparison. It also does not flag a discrepancy between a sponsor analysis and a recalculation. Accordingly, there is no alternative numerical result in the registry record to set alongside the sponsor-reported analysis. No independent recalculation should be inferred from the arm estimates alone, because doing so would require choices about variance, adjustment, and other analytical details not specified in the record.

The sponsor’s reported analysis is the relevant reported estimate, but the registry’s brief description does not fully specify the model. Its numerical result should therefore be interpreted with the stated cohort, endpoint, and analysis method in view, rather than treated as a complete account of the statistical procedure.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes and analyses. It reports 14 outcome measures and 28 analyses, with 10 secondary outcomes posted. The listed secondary outcomes include changes in QIDS, RRS short version, GAD-7, SDS, PVSS, and WHO-5 scores, as well as correlations between PHQ-9 change and playing time in MEL-T01 and MEL-S01. The primary endpoint is one comparison within this broader outcome set.

When many outcomes or analyses are examined, the chance of obtaining at least one apparently unusual result can increase. Statistical approaches to address this issue include prespecifying a primary outcome, controlling an error rate across tests, or treating secondary results as exploratory. The registry identifies a primary endpoint, but details of any multiplicity adjustment, testing hierarchy, or prespecified interpretation plan are not reported in the registry record. The primary p-value should therefore be read as the result for its stated comparison, not as evidence that all other outcomes meet the same standard.

The primary analysis is described as a per-protocol completer analysis. The record does not report the number of participants with missing PHQ-9 data, the reasons for missingness, or how missing outcomes were handled. It also does not describe imputation or sensitivity analyses for missing data. Missingness can affect interpretation if the participants with observed outcomes differ systematically from those without them; the available record does not establish whether that occurred.

The analysis population is not described as all randomized participants. The registry does not provide the full set of protocol deviations or the criteria used to define completion and per-protocol status. Those details matter when assessing which participants the estimate represents and whether exclusions could have influenced the comparison. The record’s description of pooling TAU for weeks 0–12 explains that treatment was identical during that period, but does not give further information about the statistical handling of later allocation.

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 reports zero serious adverse events among the listed risk sets: 337 in MEL-T01, 347 in MEL-S01, 153 in the TAU-first-then-MEL-T01 group, and 164 in the TAU-first-then-MEL-S01 group. Deaths are also reported as zero in each group. No top serious adverse event terms are listed.

These counts describe the posted safety record for the listed groups and risk sets. They do not establish that no serious events occurred outside the recorded definitions or observation periods, and the record does not describe event definitions, monitoring procedures, or the duration of safety follow-up. The safety group sizes and group structure also differ from the primary endpoint analysis counts, so the safety figures should not be treated as if they came from the same analysis population.

Other adverse events are reported as 52 in MEL-T01, 55 in MEL-S01, 16 in the TAU-first-then-MEL-T01 group, and 24 in the TAU-first-then-MEL-S01 group. These are counts, not rates, and should be read alongside each group’s listed risk set rather than compared as if the groups were equal in size. The record does not provide event-level descriptions for these other events in the listed summary. The absence of posted serious-event terms is a feature of the registry entry, not a complete safety assessment on its own.

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

The result describes an adjusted difference in average PHQ-9 change during Day 0 to Day 84 in the per-protocol completer cohort. The estimate is negative, and the registry’s score definition means that lower PHQ-9 scores correspond to less severe symptoms. The confidence interval is also entirely negative. These features describe the direction and statistical precision of the posted comparison between MEL-T01 and pooled TAU in the analyzed cohort.

The result does not by itself establish the clinical importance of the difference. The registry record does not report a threshold for meaningful PHQ-9 change, and an average group difference does not describe the range of individual responses. It also does not show whether score changes persisted beyond the measured period. The primary result is not a comparison of MEL-T01 with MEL-S01, even though MEL-S01 is included in the study.

The analysis does not represent every participant enrolled in the trial: the primary estimates use 99 MEL-T01 participants and 288 TAU participants, within a per-protocol completer cohort. The record does not report enough information to assess missing outcomes, exclusions, or the effect of those choices on the estimate. Randomization and quadruple masking are listed, but those design labels do not answer every question about analysis quality or applicability.

More broadly, a registry result is one part of evidence about a study. It does not supply a complete protocol, full statistical analysis plan, or all details of trial conduct. The posted figures can be interpreted as the stated model-based comparison, with its interval and p-value, while keeping its population, endpoint, and reporting limits in view. They should not be converted into advice for an individual or generalized automatically to people outside the analyzed cohort.

14. Why This Trial Matters Statistically

This trial is statistically notable for distinguishing the overall enrollment from the population used for the primary endpoint. The registry lists 1001 enrolled participants, while the reported endpoint estimates use 99 MEL-T01 and 288 TAU participants. That distinction is central: a result from per-protocol completers answers a question about the analyzed cohort, not automatically about all randomized or enrolled participants.

The record also illustrates why a treatment contrast and its uncertainty should be read together. The adjusted mean difference is -1.138, and the 90% confidence interval runs from -1.542 to -0.735. The estimate communicates the direction and scale of the average difference in PHQ-9 change; the interval conveys uncertainty around it. The p-value adds a test-based summary but does not replace either the effect estimate or its interval.

Pooling TAU participants for the first 12 weeks is another important design detail. The registry states that these participants received identical treatment during that period regardless of later allocation. That explains the primary comparison’s pooled control group for the stated endpoint, while leaving the longer-term or later-allocation comparisons outside the primary result.

Finally, the record lists several secondary outcomes and many analyses, but does not report a multiplicity strategy or detailed missing-data methods. These gaps matter when readers assess the breadth and robustness of the statistical evidence. The example shows how interpretation depends not only on a p-value, but also on the endpoint definition, analysis population, comparison structure, uncertainty, and transparency of methods.

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 estimate is explicitly based on per-protocol completers. The registry does not report the criteria for per-protocol status, the number excluded from the analysis, or the reasons participants may not have completed the endpoint. It also does not report missing PHQ-9 data or how missing observations were handled. These omissions limit assessment of whether the analyzed cohort represents the randomized groups.

The mixed models analysis is named, but the record does not give its full specification, including included covariates, model structure, or assumptions. The estimate is adjusted, yet the adjustment details are not reported. The registry also does not give the trial’s sample-size justification, planned analysis details, or any interim-analysis information. Those items should not be inferred from the posted result.

The primary endpoint covers Day 0 to Day 84, and the record provides no result about persistence beyond that period in the primary comparison. The PHQ-9 is self-reported, and the registry does not state a threshold for interpreting the size of score change as clinically meaningful. The primary result also does not compare MEL-T01 directly with MEL-S01.

Although the record lists randomized allocation and quadruple masking, it does not explain the randomization process or which parties were masked. It lists multiple outcomes and analyses but does not report a multiplicity strategy. Safety reporting gives event counts and risk sets, but not detailed event definitions or follow-up duration. Together, these reporting limits make the posted estimate interpretable as a specific registry result, but constrain broader judgments about robustness, clinical importance, and generalizability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effects of Videogames on Depression Symptoms and Brain Dynamics — NCT05426265.
• Registry record last updated 2026-04-29; status last verified 2026-04.
• Results first posted 2026-04-29.
• 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

NCT05426265 is a completed randomized, quadruple-masked, parallel study sponsored by Aalto University. It enrolled 1001 participants and lists adults with confirmed major depressive disorder as the intended population. The interventions were MEL-T01, MEL-S01, and treatment as usual.

The primary endpoint was PHQ-9 total change from Day 0 to Day 84. In the per-protocol completer cohort, the registry reports adjusted mean changes of -1.941 for MEL-T01 and -0.803 for TAU. The mixed models analysis reports an adjusted mean difference of -1.138, with a 90% confidence interval from -1.542 to -0.735 and p < 0.001.

The record also lists multiple secondary outcomes and safety counts. It does not report full model details, missing-data handling, a multiplicity strategy, or a threshold for clinically meaningful PHQ-9 change. The primary estimate should be understood in relation to its specified endpoint, comparison, and analysis population.