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Saturday, May 06, 2006

Evolution and Drug Development


After reading this article about the antibiotic drug-development pipeline, I had a thought.  
The Antibiotic Pipeline — Challenges, Costs, and Values
Richard P. Wenzel, M.D.
NEJM 351:523-526

In 2004, there are few antibacterial agents in the pipeline. Recall that in the 1930s and 1940s, four new classes of antibiotics were approved, each with novel antibacterial targets: sulfonamides, beta-lactams, aminoglycosides, and chloramphenicol. In the 1950s and 1960s, six more new classes became available (tetracycline, macrolides, glycopeptides, rifamycins, quinolones, and trimethoprim). In the 1970s, 1980s, and 1990s, however, no novel classes were licensed, and all the new drugs that became available were derivatives of existing classes. Since 2000, two new classes of antibiotics have been approved for the treatment of gram-positive bacteria: the oxazolidinones (linezolid) and the cyclic lipopeptides (daptomycin).

A relatively unfavorable return on investment is apparently deterring large pharmaceutical companies from engaging in antibiotic-drug discovery [...]
Drug companies generate candidates for drug development in a variety of ways.  Some of the candidates are developed by making random changes to existing drugs, then testing them.  As the candidates proceed through the pipeline, various economic models are used to determine which ones are worthy of additional investment.  

What occurred to me is something that might already be obvious to others; but for me, it is a new idea.  The idea is that the process of drug development could be modeled using evolutionary principles: mutation, founder effect, natural selection, and the probable mutation effect.  

The NEJM article (cited above) contains a discussion of the way in which economic models influence drug development.  This is kind of obvious: if the anticipated return on investment is low, then the incentive for developing new classes of drugs is going to be low.  However, this does not always fit with health policy priorities.  For example, we need new classes of antibiotics a lot more than we need new classes of insomnia drugs, but we currently are seeing a lot more new drugs for insomnia than for serious infections.

From the perspective of public health, it would be desirable to rearrange the incentives in drug development.  

I am wondering if a really sophisticated analysis of the drug pipeline, using evolutionary principles, could lead to some modifications of health policy.  The goal would be to modify the incentives for drug development in a way that would promote the development of drugs to meet high public-heath priorities.