Consider the following paradox: despite the declining productivity of the pharmaceutical industry, the past 20 years have been a golden age for biomedical research. We have decoded the entire human genome as well as those of most of the viruses, bacteria, and parasites that have plagued us for centuries. Our ability to understand the differences between normal and disease states has increased exponentially. New opportunities to treat hitherto intractable diseases such as Alzheimer's, cancer, and heart disease abound. Advances in imaging permit us to detect diseases that were previously hidden, often at a stage early enough for life-saving intervention. Computer models have given us powerful new tools for linking biological causes, disease effects, and probable consequences of specific treatments, while computer-driven robots allow us to sort though libraries of new drug candidates at a vastly accelerated rate. In fact, the research departments of each large pharmaceutical company produce hundreds of ideas for new drugs each year. Why, then, the slowdown in bringing these drugs to market?

I believe that it is not a failure of science but rather the context in which such science is practiced. The process of drug development is long and arduous, and throughout the entire process, a candidate is continually evaluated for market potential. At large companies, products that are technically promising are terminated if the marketing potential is thought to be too small. And the height of that market hurdle has risen as the profits of the large companies have grown. Today, programs that are thought to have an annual sales potential of less than $1 billion are usually stopped in their tracks. Some companies have abandoned their work in entire areas of medicine, such as antibiotics, because they believe the markets are too small to make a difference to their total sales.

This emphasis on the bottom line even influences the way clinical trials are designed. Companies are in a position to choose how each new drug is deployed, and drugs that are approved for limited use have limited market potential. Therefore, most clinical trials are designed to optimize sales, not to optimize the chance that a new drug will be approved for its most effective, if limited, use.

The results of this strategy are evident. Fewer than one in 100 new ideas reach clinical trials, and fewer than 10 percent of these are approved for sale. In the meantime, 10 to 12 years have typically elapsed between discovery and approval, consuming half the twenty-year patent life of each drug candidate. And when drugs are approved, problems often arise in the quest for ever-larger markets. In worst-case scenarios, the side-effects of approved drugs--perhaps tolerable in small treatment populations--are inappropriately minimized as the product is brought to mass markets. In one such instance, the drug Vioxx, approved as painkiller rather than a treatment for a smaller group of aspirin-intolerant patient, had to be withdrawn five years after it was approved by the FDA.