Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency.

Autor:	Dekker MJHJ; Dutch Medicines Evaluation Board, Utrecht, Netherlands., de Vries ST; Dutch Medicines Evaluation Board, Utrecht, Netherlands.; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands., Versantvoort CHM; Dutch Medicines Evaluation Board, Utrecht, Netherlands., Drost-van Velze EGE; Dutch Medicines Evaluation Board, Utrecht, Netherlands., Bhatt M; Dutch Medicines Evaluation Board, Utrecht, Netherlands., van Meer PJK; Dutch Medicines Evaluation Board, Utrecht, Netherlands., Havinga IK; Dutch Medicines Evaluation Board, Utrecht, Netherlands., Gispen-de Wied CC; Dutch Medicines Evaluation Board, Utrecht, Netherlands., Mol PGM; Dutch Medicines Evaluation Board, Utrecht, Netherlands.; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2021 Mar 11; Vol. 8, pp. 643028. Date of Electronic Publication: 2021 Mar 11 (Print Publication: 2021).
DOI:	10.3389/fmed.2021.643028
Abstrakt:	This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91-1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates. Competing Interests: CG-dW is a regulatory consultant since 1-1-2019. SdV and PMo had financial support from ZonMW—The Netherlands Organization for Health Research and Development and from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754425 for the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Dekker, de Vries, Versantvoort, Drost-van Velze, Bhatt, van Meer, Havinga, Gispen-de Wied and Mol.)
Databáze:	MEDLINE
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