Simulations Plus

I have been reading The Machine That Changed the World: The Story of Lean Production (1), by James Womack and others from MIT’s International Motor Vehicle Program (Content no longer available) research team. This book caused a sensation 20 years ago with its description of the Toyota Production System. The blurb on the book’s back cover says, “The hallmarks of lean production are teamwork, communication, and efficient use of resources. The results are remarkable cars with one-third the defects, built in half the factory space, using half the man-hours.”

Why is it so hard to incorporate modeling and simulation into drug development? Why do these powerful tools so often fail to provide satisfactory outcomes?

In December 2009, The Wall Street Journal sponsored its second Future of Finance Initiative (links to a dead page) to provide a forum for 80 of the world’s top financiers to brainstorm suggestions for reforming the financial system in the wake of the 2008 implosion of the global economy.

I have become addicted to David Foster Wallace’s nonfiction essays, several of which were published in A Supposedly Fun Thing I’ll Never Do Again.*

Part 1
The CEO of a pharmaceutical company, tired of late-stage development failures and FDA questioning regarding dose selection, decides to act on the promise of pharmacometrics. “Fix it,” he says to the head of clinical pharmacology, “I don’t care what it takes!” The clinical pharmacologist agrees to take on the challenge and asks for a data programmer and pharmacometrician. Seizing on an opportunity to spearhead an upcoming “end of phase 2” meeting with the FDA, the pharmacologist quickly sketches out his strategy for the modeling activities required for dose selection and justification. He then instructs his programmer to assemble the required dataset using the data from several phase 1 studies and a recently completed phase 2 study. A week later he discovers that the modeling has not begun because the dataset is still not ready. “What is taking so long?” he wonders.