title: Parallel discovery of Alzheimer's therapeutics.
abstract: As the prevalence of Alzheimer's disease (AD) grows, so do the costs it imposes on society. Scientific, clinical, and financial interests have focused current drug discovery efforts largely on the single biological pathway that leads to amyloid deposition. This effort has resulted in slow progress and disappointing outcomes. Here, we describe a "portfolio approach" in which multiple distinct drug development projects are undertaken simultaneously. Although a greater upfront investment is required, the probability of at least one success should be higher with "multiple shots on goal," increasing the efficiency of this undertaking. However, our portfolio simulations show that the risk-adjusted return on investment of parallel discovery is insufficient to attract private-sector funding. Nevertheless, the future cost savings of an effective AD therapy to Medicare and Medicaid far exceed this investment, suggesting that government funding is both essential and financially beneficial.
authors.affiliation: Massachusetts Institute of Technology (MIT) Sloan School of Management and Laboratory for Financial Engineering, Cambridge, MA 02142, USA. MIT Computer Science and Artificial Intelligence Laboratory and Department of Electrical Engineering and Computer Science, Cambridge, MA 02142, USA. AlphaSimplex Group, Cambridge, MA 02142, USA. alo@mit.edu.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lo
authors.affiliation: Early Clinical Development, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Ho
authors.affiliation: Massachusetts Institute of Technology (MIT) Sloan School of Management and Laboratory for Financial Engineering, Cambridge, MA 02142, USA.
authors.forename: Jayna
authors.initials: J
authors.lastname: Cummings
authors.affiliation: Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D003299:Cooperative Behavior; D003362:Cost-Benefit Analysis; D055808:Drug Discovery; D006801:Humans; D017149:Private Sector; D017150:Public Sector