The data from clinical trials included in the package inserts of coagulation factors used for the treatment of hemophilia A and B frequently harbor methodologic or clinical biases, according to the results of study published in the journal Einstein.

“The quality of scientific evidence available on the efficacy of medicines containing coagulation factors used in the treatment of hemophilia needs to be carefully analyzed and interpreted,” the authors wrote.

In the study, the authors identified the package inserts of 7 coagulation factors for the treatment of hemophilia registered with the Brazilian Health Regulatory Agency and evaluated the clinical trials cited. The trials were analyzed for methodologic quality.

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The 7 package inserts cited 10 studies that were eligible for analysis.

A control group was not present in 50% of the studies. Of the trials with a control group, the publication did not report the performance and/or methods of patient randomization and allocation.

“These two steps are essential in a clinical trial to alleviate selection bias, thus providing baseline similarity,” the authors wrote in their report. In the 5 studies with control groups, 2 blinded the outcomes to the evaluators and 3 were double-blinded.

Biases of selection, performance, and detection were not controlled for in more than 50% of the studies, and 50% had a high risk of conflict of interest. However, attrition and reporting biases were adequately controlled in all studies analyzed.

The authors concluded that “the biases present are significant and may have influenced the overestimation of the effects of the outcomes of each of the studies.”


Araujo YG, Paolinelli JPV, Pichitelli JSD, et al. Quality of clinical studies present in the package inserts of coagulation factors used in the treatment of hemophilia. Einstein (Sao Paulo). 2022;20:eAO6859. doi: 10.31744/einstein_journal/2022AO6859