Drug Discovery over the Past Thirty Years: Why Aren’t There More New Drugs?

The rate of drug discovery has not kept pace with the exponential increase in biomedical knowledge. For the past 30 years, the number of new molecular enti- ties approved by the United States Food and Drug Administration has averaged 20 to 30 drugs per year, except for a peak in the mid-1990s that briefly doubled this rate. This modest productivity cannot be explained by lack of funding, as the research budgets of government and industry-funded programs have increased threefold to fivefold over the past three decades. Various arguments have been proposed to account for the relative lack of innovative new drugs, but little consideration has been given to the focus on hypothesis-driven translational research. In theory, the emphasis on translational research should have led to an increase in the number of new drugs. However, in considering the historical perspective of drug discovery and the role of serendipity, it can be argued that the emphasis on translational research diverts scientists from pursuing basic-science studies that give rise to fundamental discoveries. In many cases, retro-translational research (from clinic to basic science) is necessary before the disease process can be understood well enough for scientists to develop therapeutics. Ultimately, a balance of disease-oriented and basic-science research on fundamental processes is optimal.