Developing drug prototypes: pharmacology replaces safety and tolerability?

• Published in: Nature reviews. Drug discovery Vol. 9; no. 11; pp. 856 - 865
• Main Author: Cohen, Adam F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2010; Nature Publishing Group
• Subjects: 631/154/436; 692/308/153; 706/703/66; Animals; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Clinical trials; Clinical Trials as Topic - adverse effects; Clinical Trials as Topic - trends; Drug Discovery - trends; Drug-Related Side Effects and Adverse Reactions; Humans; Management; Maximum Tolerated Dose; Medicinal Chemistry; Molecular Medicine; opinion-2; Pharmacology, Clinical - trends; Pharmacology, Experimental; Pharmacology/Toxicology; United States; United States Food and Drug Administration - trends; United States
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/nrd3227

Currently, drug development is based on a consecutive phase model and Phase I clinical trials often have tolerability as their primary objective. Here, Cohen advocates new concepts for drug development that are based on pharmacological knowledge about the effects of the drug and an adaptive, cyclical development process. New medicines are designed to bind to receptors or enzymes and are tested in animal cells, tissues and whole organisms in a highly scientific process. Subsequently they are often administered to human subjects with tolerability as the primary objective. The process of development is considered to be linear and consecutive and passes through the famous four phases of development (Phase I– Phase IV). This is efficient for those projects for which the uncertainty about the development is low. There is, however, an increasing number of new prototypical compounds resulting from the increased biological knowledge with a high level of uncertainty. For these prototypical drugs development has to proceed in a much more adaptive manner, using tailor-made objectives, the development of special methodology and a cyclical rather than a linear type of project management.