These two papers should really make you think. First, in 2004 Pharmacia, submitted lists of compounds to their medicinal chemists to select as part of a compound acquisition initiative. By sending multiple lists (rather than one big list) it was possible to look at the consistency of the chemists in their selection choices. While the authors expected a difference between chemists, they did not expect an individual chemist to be inconsistent between each list. This is food for thought. In Novartis in 2012 sent multiple lists of compounds, but in addition the chemists were asked on what criteria they had chosen the compounds i.e. lipophilicity, size, diversity, novelty. The expectation was that calculations and filters would be applied to reduce the lists to a smaller sets to review by eye. From the returned selections it was possible to look at the spread of these properties. The actual selections did not reflect the criteria the chemists had said they used. Of most concern, nearly all chemists said they used novelty as a select, but only 2 of the 19 actually selected novel compounds. Overall, both studies showed considerable bias in compound selection, again considerable food for thought.
Assessment of the Consistency of Medicinal Chemists in Reviewing Sets of Compounds. J. Med. Chem. 2004, 47, 20, 4891–4896
Inside the Mind of a Medicinal Chemist: The Role of Human Bias in Compound Prioritization during Drug Discovery. PLoS ONE 7(11): e48476.