payers spend less on ineffective therapies. “We see opportunities not just for developers and patients, but for everyone in the cycle. … It has to work for everyone or it is not going to work at all as a system.”

Both Ginsburg and Davies said that a genomic-based approach continues to have tremendous potential. For example, a recent analysis of genome-wide association studies (GWAS) found that such studies can reveal new pathways involved in complex diseases and suggest potential therapeutic options that had not previously been considered for those indications (Collins, 2011). This analysis also suggested that the off-target or adverse effects of those drugs could be monitored through the analysis of genes discovered through these unbiased genome-wide approaches.

Garret FitzGerald of the University of Pennsylvania added that it has already been demonstrated that genetic information can be used to evaluate adverse drug effects. Studies designed specifically to determine whether particular gene variants can be used to identify individuals at particular risk have been successful for both lumiracoxib and abacavir and required only very small numbers of study participants to do so.

According to recent data from the U.S. Food and Drug Administration (FDA), more than 110 marketed drugs have pharmacogenetic biomarkers on the label (see Table 2-1),1 and the need for further drugs developed through a genomic-based approach remains strong. As Trusheim observed, many major drugs, including hypertension drugs, heart failure drugs, antidepressants, cholesterol drugs, and asthma drugs, are ineffective for large portions of the population (Spear et al., 2001). Furthermore, ineffective therapies cause substantial harm. Medication-related health problems account for an estimated 3 to 7 percent of hospital admissions (Pirmohamed et al., 2004), and 15 percent of patients experience an adverse drug reaction during hospital stays. An important consequence of these adverse reactions is heightened patient noncompliance.

Oncology has made the most progress in developing personalized medicine (defined in Box 2-1), Davies said, but genomic-based research is also starting to make progress on diseases of the cardiovascular system, central nervous system, and immune system. Metabolic, respiratory, and viral diseases also are starting to yield to this approach, though progress has been slower than expected.

Pharmaceutical companies and biotechnology companies are striving to modernize their drug discovery and development processes. Davies pointed to data from the Tufts Center for the Study of Drug Development (Tufts, 2010) showing that 100 percent of surveyed companies are using a discovery strategy that involves a genetic or genomic approach. Thirty percent

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1 For an up-to-date listing of these drugs, see http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm.



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