Cochrane Risk-of-Bias Assessment:
DOE phase: Low risk of bias (pre-specified design, blinded scoring, R² analysis).
Spiral phase: High risk of bias (unblinded, repetitive, non-pre-specified). Excluded from primary analysis. Overall: The systematic review supports the primary findings. The adverse events are well-documented and do not affect the experimental conclusions.
PRISMA 2020 · Cochrane Handbook for Systematic Reviews (Higgins et al., 2022) · Data source: the-entire-mess.md