Simulations Plus

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.

A kerfuffle is the polite term for a cascading series of errors that can be initiated by a seemingly innocuous event that then leads to other errors that seem to gain in severity and impact. Kerfuffles can appear in any line of work or play that involves a linked series of tasks with downstream implications. In fact, the modeling and simulation activities performed to support model-based drug development have the potential to produce a catalogue of kerfuffles that can culminate in the failure to deliver modeling and simulation results when they are needed for decision-making. Kerfuffles often have their origins in inadvertent oversights committed early in the study design and data collection process or in the commonplace shortcuts taken to deliver preliminary (“quick-and-dirty”) results for internal use.