Simulations Plus

If you want to understand process formalization, read Jane Austen.

As you study the blue ball machine, it is easy to see how you can be mesmerized by a process that doesn’t actually do anything. See if you can find the part where the ball replaces the worker’s head. Then find the little sign that every now and then flashes NO. It never says yes

I first came across the word “disambiguation” at a weekend workshop called Ontology in Science. (There is so much that’s just wrong about what I just admitted, but never mind.) I like this word a lot because it makes people ask, “for goodness sake, what are you talking about?” But disambiguation is a serious word, especially in science. It means “to remove ambiguity.” Once you learn that there is a word for getting rid of ambiguity, you begin to realize how much ambiguity there is in the world, especially when people communicate. And it seems to me that the smarter the people and the more complex the topic, the more disambiguation is necessary.

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.

A crusading scientist identifies a potential public health threat and uses the internet to get access to a cache of data from several studies. After a quick analysis of the pooled data, he reports a previously unrecognized adverse effect of a widely used drug. Patients and physicians become alarmed, and the drug is pulled from the market. Sound like the plot of a new medical thriller? In fact, a similar scenario has hit the headlines several times in the last 10 years. Each time, controversy about the validity of the analysis and conclusions was loud and lasting.

Chapter 3 of 3. Need to catch up? Read Part 1 and Part 2 of the series.

The word “globalization” can be interpreted many ways, both positive and negative. In these uncertain economic times, many people think globalization is equivalent to job loss and trade protectionism.

I recently stumbled on a website called TED: Ideas worth spreading, and I apologize in advance for sharing this most addicting site with you.

I stumbled upon the remarkable autobiography of Henry Adams by accident while reading a history of the end of the 19th century. When Adams’ autobiography was published after his death in 1918, it became a best seller and won the Pulitzer Prize. Adams is remarkable for his ability to speak to us more than 90 years later with a message that is both relevant and moving.

I found that I was getting into a musical rut and had a hard time finding new music I liked. Then I stumbled on Pandora Internet Radio. On Pandora, you create your own “radio station” by naming a favorite song or artist. Pandora scans thousands of pieces of music that have been analyzed by something called the Music Genome Project to identify those with similar attributes to the one you named. Voilà! New music for you to enjoy.

Languages, even seldom-used languages, can tell us a great deal about how a group of people categorize the natural and mental world, says Jeff Good, a linguistics professor at the State University of New York at Buffalo (1). Languages are rich in the history and taxonomy of a place, reflecting subtleties that can be lost in translation, says Greg Anderson, an ethnographer who directs Oregon’s Living Tongues Institute (2). When the last keepers of a language die off, so does the fluent understanding of that particular environment.

Jazz had a largely unappreciated role in hastening the arrival of the civil rights movement, according to veteran jazz writer Nat Hentoff. As early as the 1920s, white and black jazz musicians played together in after-hours jam sessions. But it was not until the 1940s, Hentoff said in the January 15, 2009, issue of the Wall Street Journal, that jazz musicians and their audiences mixed publicly in clubs—tentatively at first, but then freely and openly, in violation of local laws and mores. As jazz captured more and more avid listeners, white Americans started to understand the effect of segregation in all aspects of American culture.

In Dan Carlin’s Hardcore History podcasts, the past is twisted and turned upside down in novel and intriguing ways. Dan Carlin, a veteran journalist and radio talk show host, emphasizes the drama of past events and personalities to reveal why history matters today.

Chapter 2 of 3. Need to catch up? Read the previous post in the series.

Several large Pharma companies have announced interest in acquiring small biotech companies. Many Pharma companies have reduced or eliminated drug discovery efforts, and with stock prices back at 2003 levels, there certainly is a great deal of sense in these acquisitions. But finding another way to integrate these companies and their development portfolio also makes a great deal of sense.

John Muir was one of the first climbers to explore and climb many of the peaks in Yosemite Valley in California’s High Sierra. During his first ascent of Mount Ritter in 1872, he became gripped with fear.