Sex as a variable in medicines assessment reports for licensing in the European Union. Can gender bias be excluded?

To analyse publically available official reports on the evaluation of European Union (EU) registration of new medicines (aimed at diseases affecting both sexes) in order to address the possibility of gender bias.

Descriptive study reviewing two types of assessment reports corresponding to different EU registration procedures: European Public Assessment Reports (EPARs) for the centralised procedures (399 reports considered from 2001 to 2002 and 2008 to 2009) and Mutual Recognition or Decentralised Public Assessment Reports (MPARs) for the mutual recognition and decentralised procedures (2,704 reports, totality until 2009-inclusive).

Two hundred and twenty-four EPARs fulfilled the study criteria. It can be deduced from those EPARs that women participated in at least one clinical trial in 215 (78.5 %) of the reports. In 49(17.9 %) of the EPARs, the study population is explicitly evaluated according to sex, ten (3.6 %) presenting results disaggregated by sex. Most sex-related differences are in safety and pharmacokinetics; six of the 22 cases (72.7 %) of safety differences and nine of the 23 cases (60.9 %) of pharmacokinetic differences are not discussed. In relation to MPARs, only 2,704 out of 15,621 registries (17 %) were published, which casts doubts on the representativity of the available reports. Those published reflect less participation by women than in the EPARs.

From the incomplete sex-related data made public, it is difficult to conclude on the existence of gender bias in the evidence used for the evaluation of new medicines. It certainly cannot be excluded. It is therefore recommended that compliance with existing guidance for publication of reports is increased, so as to transparently reassure on the issue.