Supporting the Primary Outcomes of the Mirai Trial for the Adjunctive Digital Therapeutic Rejoyn (CT-152) in the Treatment of MDD: Meaningful Change Analysis in the Montgomery-Åsberg Depression Rating Scale (Preprint)
Bibliographic record
Abstract
Background: Rejoyn (CT-152) is a prescription digital therapeutic (DTx) adjunct to antidepressive medication authorized for patients with major depressive disorder. To better understand the patient benefit of DTx and other treatment modalities, current regulatory standards support the use of modern psychometric methods to interpret the clinical meaningfulness of treatment effects for patients. In the primary analysis of Rejoyn from the pivotal phase 3 Mirai trial (NCT04770285), Rejoyn showed a broad risk-to-benefit profile as demonstrated on multiple clinician- and patient-rated scales, including the primary efficacy outcome measure, the Montgomery-Åsberg Depression Rating Scale (MADRS). These findings supported US Food and Drug Administration authorization of Rejoyn as a prescription DTx. However, the clinical relevance of these changes in the MADRS score is not immediately interpretable in clinical practice. Here, we present the results from several post hoc analyses of the Mirai trial data to support the interpretation of clinically meaningful treatment differences on clinician- and patient-reported change in depressive symptoms. Objective: This study had two main objectives: (1) establish threshold parameters that allow for clinically meaningful interpretation of the Mirai results in clinical practice, based on the clinical trial end points of change from baseline in depressive symptoms, and (2) apply this threshold in a responder and sensitivity analysis in the intent-to-treat (ITT) population (which is more frequently reported in pharmacological trials) to further support the interpretation of change in unblinded analysis of the Mirai results. Methods: For the Mirai meaningful within-patient change (MWPC) analysis, anchor-based methods were used to define an MWPC threshold by exploring the associations between the MADRS and the clinician-rated Clinical Global Impression-Severity Scale (CGI-S) and the patient-reported Patient Health Questionnaire 9-Item Scale (PHQ-9). Additional post hoc efficacy analyses (including that of responders) are reported for the ITT population. Results: Using the MWPC thresholds of 8 and 10 points (derived with the CGI-S and PHQ-9 as anchor measures, respectively), the distribution of MADRS responders favored the Rejoyn group over the sham group, and the Rejoyn group had 24%-47% higher odds of meaningful improvement on the MADRS. Post hoc ITT analyses also favored the Rejoyn group over the sham group for response rates and PHQ-9 and CGI-S score change from baseline. Conclusions: Results are consistent with the primary findings of the Mirai trial, supporting the efficacy of Rejoyn as an adjunctive treatment to antidepressive medication monotherapy for adults with major depressive disorder. The MWPC analyses offered a measure of meaningful change on the MADRS, providing a framework of clinical meaningfulness for the Mirai trial findings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.023 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.005 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.006 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".