In the recent article of eClinicalMedicine,1 the authors demonstrate that high-dose intravenous immunoglobulin may be effective in recurrent pregnancy losses (RPL). This achievement in an area where double-blind randomised controlled trials are difficult to conduct is to be applauded. On the other hand, we would like to point out two areas in the article that may cause misunderstanding and reduce the value of it.
First, the article refers to the trial as phase II, but the registration details on Clincialtrials.gov2 and the clinical study protocol in the supplementary materials refer to it as phase III, which is inconsistent.
Second, the study protocol clearly states that the primary efficacy analysis set is modified-intention-to-treat (m-ITT), as the target number of patients for efficacy evaluation is set based on the m-ITT.
Although the protocol says that the same analysis will be performed for ITT, we believe that in general, phase III trials should clearly state what the primary efficacy analysis set is and present the main analysis results. The way in which the authors mainly describe the results of the ITT analysis, which is a secondary analysis, might lead to readers’ misunderstanding.
Contributors
H.Y. conceived this manuscript and wrote the original draft. H.S. reviewed and edited this manuscript. All authors accepted responsibility to submit for publication.
Declaration of interests
The authors declare no conflicts of interest associated with this manuscript.
References
- 1.Yamada H, deguchi M, Saito S, et al. Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: a double-blind, randomized, placebo-controlled trial. eClinicalMedicine. 2022;50 doi: 10.1016/j.eclinm.2022.101527. (Published online 28 June 2022) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Study of the efficacy and safety of GB-0998 in patients with unexplained recurrent miscarriage. Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02184741. Accessed online 1 August 2022.