Baloxavir Marboxilに関するレター。

NEJMにレターを書いたのですが残念ながらリジェクトされたのでブログに。「治療薬に関連した副作用」が恣意的に決められていないか、という疑問と、なぜかプラセボよりも副作用が少ないのはなぜ？という疑問でした。なんでなんでしょうね。

 

To the editor.

I read the article with interest by Hayden et al investigating the effects of baloxavir marboxil on uncomplicated influenza.1 However, there are some uncertainties regarding adverse effects reported.
According to the article, adverse events related to the trial regimen were more common in oseltamivir recipients than in baloxavir or placebo recipients in phase 3 study. Study protocol states that the relationship was determined by the investigators or subinvestigators, based on reasonality to explain that the study drug caused adverse effects. With this rather arbitrary definition, I was not certain how precisely the "events" were determined to be "related". Since data on this study were "compiled by the sponcer and analyzed by a statistician employed by the sponcer", was there any room of bias in selecting these "related" events? 1
In addition, Overall incidence of adverse events in baloxavir group appeared lower than placebo (20.7% vs 24.6%), with p value of 0.20 by my calculation. While the one for oseltamivir were comparable (24.8%), I wonder why baloxavir group had lower adverse effect than placebo.

1. 
   Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. New England Journal of Medicine. 2018;379:913–23.

2018.10.16 追記　NEJMにはアクセプトされませんでしたが、レターは著者に転送されていて、Dr. Haydenより丁寧な御返事をいただきました。AEの評価をしている評価者がブラインドされている点と、プラセボ群でAEが少なかったのはおそらくはAEとされたのが実はインフルの症状で、それが治ったからではないか、という趣旨でした。made senseだと思い、その旨お返事しました。