title: Longitudinal trends and subgroup analysis in publication patterns for preclinical data of newly approved drugs.
abstract: Having observed a large variation in the number and type of original preclinical publications for newly registered drugs, we have explored whether longitudinal trends and/or factors specific for certain drugs or their manufacturers may explain such variation. Our analysis is based on 1954 articles related to 170 newly approved drugs. The number of preclinical publications per compound declined from a median of 10.5 in 1991 to 3 in 2011. A similar trend was observed for the number of in vivo studies in general, but not in the subset of in vivo studies in animal models of disease. The percentage of compounds with studies using isolated human cells or cell lines almost doubled over time from 37 to 72%. Number of publications did not exhibit major differences between compounds intended for human versus veterinary use, therapeutic areas, small molecules versus biologicals, or innovator versus follow-up compounds; however, some companies may publish fewer studies per compound than others. However, there were qualitative differences in the types of models being used depending on the therapeutic area; specifically, compounds for use in oncology very often used isolated cells and cell lines, often from human origin. We conclude that the large variation in number and type of reported preclinical data is not easily explained. We propose that pharmaceutical companies should consistently provide a comprehensive documentation of the preclinical data they generate as part of their development programs in the public domain to enable a better understanding of the drugs they intend to market.
authors.affiliation: Klinik für Kleintiere, Tierärztliche Hochschule Hannover, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Köster
authors.affiliation: Klinik für Kleintiere, Tierärztliche Hochschule Hannover, Hannover, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Nolte
authors.affiliation: Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. marmiche@uni-mainz.de.|Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Str. 67, 51101, Mainz, Germany. marmiche@uni-mainz.de.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000826:Animal Testing Alternatives / Q000639:trends; D000818:Animals; D015706:Bibliometrics; D001681:Biological Assay / Q000639:trends; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical / Q000639:trends*; D006801:Humans; D008137:Longitudinal Studies; D010506:Periodicals as Topic / Q000639:trends*; D010599:Pharmacokinetics; D012107:Research Design / Q000639:trends*; D013997:Time Factors; D018675:Toxicity Tests / Q000639:trends; D014481:United States; D014486:United States Food and Drug Administration
keywords: Animal model; Drug development; Preclinical research; Publication strategy