PASSReviewer 1· 90% conf
The study design is rigorous with randomization, blinding, power analysis, and prespecified analyses, though some elements like independent replication are not applicable.
Evidence
paraphrase[Methods, Randomization and masking]
“In both Part B cohorts, treatment-naive individuals were randomized 2:1 to receive 50/28 mg (investigational group) or 12/12 mg nusinersen (control group), respectively. Randomization was stratified according to disease duration for the cohort with infantile-onset SMA (≤12 weeks and more than 12 weeks from age at symptom onset to age at informed consent), and according to age at informed consent for the cohort with later-onset SMA (<6 years and ≥6 years).”direct quote[Methods, Procedures]
“For the dosing days that were not common between the nusinersen regimen, participants received a sham procedure in lieu of a lumbar puncture and dosing to ensure that the blind was maintained.”direct quote[Methods, Statistical analysis]
“A sample size of approximately 50 participants in the 50/28 mg group was estimated to provide at least 99% power for the primary endpoint to detect an improvement of 24 points on CHOP-INTEND and a 23% survival rate benefit (versus the matched sham group from ENDEAR) at day 183, based on the joint-rank test at a two-sided significance level of 0.05.”PASSReviewer 2· 90% conf
The trial design is rigorous with randomization, blinding, prespecified matching, and a power analysis for the primary endpoint, though some elements like independent replication are not applicable.
Evidence
direct quote[Methods, Randomization and masking]
“In both Part B cohorts, treatment-naive individuals were randomized 2:1 to receive 50/28 mg (investigational group) or 12/12 mg nusinersen (control group), respectively.”direct quote[Methods, Statistical analysis]
“A sample size of approximately 50 participants in the 50/28 mg group was estimated to provide at least 99% power for the primary endpoint to detect an improvement of 24 points on CHOP-INTEND and a 23% survival rate benefit (versus the matched sham group from ENDEAR) at day 183, based on the joint-rank test at a two-sided significance level of 0.05.”direct quote[Methods, Procedures]
“For the dosing days that were not common between the nusinersen regimen, participants received a sham procedure in lieu of a lumbar puncture and dosing to ensure that the blind was maintained.”