Bipolar Disord. 2021 Jul 2. doi: 10.1111/bdi.13109. Online ahead of print.
ABSTRACT
We read the article by Ahmad et al1 with great interest. The study concluded that endoxifen is efficacious and safe in patients with acute manic episodes with/without mixed features. However, we are worried about internal and external validity of study results. We have reservations about the sample size estimation, statistical analysis, and missing data handling. Sample size, in a randomized clinical trial depends on the study hypothesis, i.e., superiority, non-inferiority or equivalence of two treatments. The efficacy endpoints briefly mentioned “endoxifen was considered non-inferior to divalproex if the lower limit of 95% CI was greater than -10,”-suggested a possibility of non-inferiority design. However, the “non-inferiority margin” was not based on statistical considerations.2 Moreover, we did not find any mention of non-inferiority between endoxifen and divalproex in the article, except for a passing remark. Further, in a multicentric study, between-centre heterogeneity needs to be accounted for in the sample size calculation and in analysis.3 Extremely unequal centre enrolment and apparent heterogeneity in practice (use of rescue medication only in one centre) added to this concern further.
PMID:34214241 | DOI:10.1111/bdi.13109
