Drug discovery and development has evolved in an accelerated fashion
during the latter half of the 20th century and the first decade of the
21st century from the serendipity of folk medicine and herbal remedies to a
more refined observational and hypothesis-driven biological approach and
finally to the present-day translational approach that relies on an understanding
of disease and human biology at a molecular level. Advances in
information, molecular and biomarker technologies, and quantitative systems
pharmacology have further enabled this rapid evolution. Along with
these important advances and changes, however, has come an unsustainable
attrition rate that has increased the cost of discovering and developing
new drugs and threatens the future of the pharmaceutical industry as
we have known it. The combination of modern, science-driven translational
drug discovery and development and unsustainable attrition rates
has created a new reality that has had its greatest impact on the earliest
stages of drug development. This reality ismandating changes in strategies,
technologies, and disciplines in an effort to improve confidence and the
success rate of new drug targets, mechanisms, and molecules. Ultimately,
these changes are designed to affect the endgame: improved productivity
in terms of new drug approvals for unmet medical needs at a sustainable
cost from themodern drug discovery engine.