Trial Limitations

The multicentre structure is described as increasing generalisability relative to a single-site design. The study design is described as practical and reproducible. Coronary CT angiography in about 80% of participants is intended to help identify CAC-zero patients with non-calcified atherosclerosis. SIDAS treats suicidal ideation as a linear severity score despite real-world fluctuation. Centre-dependent treatment allocation may limit generalisability to institutions without the required radiotherapy infrastructure. The study had short follow-up, small patient numbers, and ended early before the planned phase 2a expansion cohort was completed. Larger studies with longer follow-up are needed to determine long-term safety and relapse-prevention efficacy. Several planned exploratory analyses were not analyzed. The trial cannot distinguish whether higher on-treatment renin reflects MRA efficacy or milder, more MRA-sensitive disease. The broad high-risk eligibility criteria created a heterogeneous population that made historical survival comparisons difficult. DERS may be less sensitive to distress-management capabilities because investigators selected it rather than co-designing it wi…