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.

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

“…Each novel drug is classified based on its innovation status as defined above (Table 1 ) and on the type of agent (small molecule, antibody, and peptide, and DNA/RNA-related: Table 2 ). As observed previously (Koster et al 2016b , 2016a ), we found a very heterogeneous reporting of data on novel entities in the peer-reviewed literature with regard to type and quantity of data being disclosed and to the number of publications. For ease of reading, we have organized our subsequent discussion by therapeutic areas.…”

Opportunities and Challenges for Drug Development: Public–Private Partnerships, Adaptive Designs and Big Data

“…Academic investigators engaged in non-clinical drug-related research expressed strong interest in such collaborations (Amiri and Michel, 2015). In a systematic analysis of non-clinical publications presumably reflecting work performed concomitant with commercial drug development, 75% of all such publications had a corresponding author from academia (Köster et al, 2016b). Thus, project-based collaborations between pharmaceutical companies and individual academic groups are an important component of translational drug development, but the specific needs and approaches may vary considerably between projects, even within a company (Köster et al, 2016a).…”