title: Preclinical research strategies for newly approved drugs as reflected in early publication patterns.
abstract: The present study aimed to explore early publication patterns (i.e. up to 1 year after obtaining regulatory approval) for newly registered drugs. From the website of the US Food and Drug Administration, all newly approved drugs for 6 calendar years between 1991 and 2011 were identified. Non-clinical original publications for these compounds were retrieved from PubMed and their abstracts analysed for type of study and reported data. This yielded 170 compounds for which 1954 original non-clinical publications were identified, i.e. a median/mean of 5/11.5 publications per compound; however, number of publications per compound varied widely (0-90) and this variation exhibited a non-Gaussian distribution. The earliest non-clinical publication typically was published less than 5 years before regulatory approval and more than 5 years after filing of the primary patent, but some compounds exhibited notable deviations from this pattern. Publications most often reported on efficacy related to the target indication and on potential future indications, with fewer studies addressing mechanisms of action, potency, selectivity, pharmacokinetics and toxic effects. For most compounds, data at the cellular and in vivo level were published, with fewer reports on effects on isolated tissues and even fewer at the molecular level. The preferred species for cellular studies was human, whereas for in vivo studies, it was rats and mice. In 75 % of cases, the lead author of the publication came from an academic institution, and most studies were published in classic pharmacology journals. We conclude that number, timing and scope of early non-clinical publications on newly approved drugs exhibit major variance. Factors potentially associated with such variance are explored in a companion paper.
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: D000818:Animals; D015706:Bibliometrics; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical / Q000639:trends*; D006801:Humans; 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