Requesting data for a presentation [General Sta­tis­tics]

posted by Helmut Homepage – Vienna, Austria, 2023-02-23 11:46 (36 d 18:28 ago) – Posting: # 23471
Views: 4,103

Dear all,

I’m also collecting data to assess a ‘Sex-by-Formulation interaction’ because in Section 2.1.1 of ICH M13A we find:

Subjects should be at least 18 years of age and preferably have a Body Mass Index between 18.5 and 30.0 kg/m2. If a drug product is intended for use in both sexes, it is recommended the study include male and female subjects. […] Subjects should preferably be non-nicotine users.


Obviously there are no concerns about extrapolating results to patients < 18 years, to obese patients (in the US a whopping 42% of the adult population), or to 23% of adults smoking tobacco. However, this sentence is similar to what the FDA recently recommended but is not stated in any other of the global guidelines. Where does this come from and why? We have only few anecdotal reports and small meta studies with contradicting results. Nevertheless, authors of the largest one concluded:1

There is no evidence to require studies in both sex groups, combined or separately.

In the past the majority of studies were performed in males only. We know that pharmacovigilance is not very sensitive. However, in 23.8 million drug switches in The Netherlands only 1,348 ADRs were reported…2

I will give a presentation at Medicines for Europe’s 2nd BE Work­shop. This is what I have so far (205 mixed-sex datasets, 170 passing BE for AUC; 3,380 males, 2,778 females):

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Preliminary results:

  1. González-Rojano E, Marcotegui J, Ochoa D, Román M, Álvarez C, Gordon J, Abad-Santos F, García-Arieta A. Investigation on the Existence of Sex-By-Formulation Interaction in Bioequivalence Trials. Clin Pharm Ther. 2019; 106(5): 1099–112. doi:10.1002/cpt.1539.
  2. Glerum PJ, Neef C, Burger DM, Yu Y, Maliepaard M. Pharmacokinetics and Generic Drug Switching: A Regulator’s View. Clin Phar­ma­co­kin. 2020; 59: 1065–9. doi:10.1007/s40262-020-00909-8.

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Helmut Schütz
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