Explanation for the choice of comparators {6b}
PPH, ICH
EMA
The I’M WOMAN trial has an active control (IV tranexamic acid) and a placebo control group. A three-arm trial with experimental treatment, active control and placebo group is considered the gold standard non-inferiority design by drug regulatory agencies and is strongly recommended by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and European Medicines Agency (EMA). The IM and IV tranexamic acid groups will be compared to assess non-inferiority. The placebo group will be compared to the tranexamic acid groups to confirm assay sensitivity and provide evidence about the effects of tranexamic acid on PPH prevention. While tranexamic acid is recommended for the treatment of PPH, it is not recommended for prevention, and the balance of benefits and risks in women giving birth remains uncertain based on existing evidence, so a placebo arm is ethically and scientifically justified.