Simulations Plus

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Pharmacometric modeling and simulation has moved from its infancy as a novel way of approaching the analysis of clinical pharmacokinetic data to become an invaluable tool in pharmaceutical and biotechnology research and development.

This year represents the 60th anniversary of the publication of the famous paper by James Watson and Francis Crick proposing a structure for DNA. This podcast from Nature contains interviews with scientists who were actively involved in the race to work out the structure. Listen to the podcast. At approximately 7 minutes into the podcast, there is a remarkable description of Watson’s first look at the classic x-ray crystallography picture of DNA. Watson knew immediately what the picture represented because Crick had, two years previously, published a theoretical paper about what a helical diffraction pattern
would look like.

Buffalo is home to truly spectacular architecture. We have many landmark buildings, historic sites, and cultural attractions and to appreciate them is to be reminded that Western New York was once at the cutting edge of architecture and landscape design that served to make Buffalo an aesthetically pleasing place to live and work. These works of art were conceived and built during a time of remarkable wealth generated as a result of Buffalo’s location at the western terminus of the Erie Canal and a transportation hub for goods moving between the Mid-West and East Coast.

“Thirty minutes until system shut-down” was the announcement over the loudspeaker that signaled the start of the move to new office space.

Are you a whistle-blower? Or do you cringe just to read those words? According to Margaret Heffernan* (links to a dead link) in a 2012 TEDTalk, most whistle-blowers are good guys. A whistle-blower can provide constructive conflict, which is vital for success. Heffernan says that great research teams, relationships, and businesses allow people to deeply disagree. When we are afraid of conflict, our doubts remain hidden. But when we dare to break that silence – when we dare to create conflict – we enable ourselves and the people around us to do our very best thinking.

Reviews of new drug applications by regulatory authorities worldwide grow ever more rigorous. I think that one reason for this heightened scrutiny is that reviewers have, over the last 10 years, read many submissions containing results of pharmacometric modeling and simulation analyses. With the use of modeling, explorations of the determinants of drug efficacy and safety are more thorough, and the analyses provide solid support for dose recommendations and labeling content. In short, I think that model-based analyses have raised reviewers’ expectations.

Brené Brown is a researcher at the University of Houston who studies vulnerability, courage, authenticity, and shame.* She speaks to many different audiences, including corporations and universities. Often, the person arranging a presentation timidly suggests that it might be better if she does not mention vulnerability or shame in her presentation. When asked what they want to hear about, the reply is “innovation, creativity, and change.” Her emphatic retort is that, “vulnerability is the birthplace of innovation, creativity and change!” To learn more, watch her second TEDTalk, Listening to Shame, here:

During World War 2, a federal excise tax was imposed on supper clubs to raise funds from their wealthy patrons. According to Eric Felton in The Wall Street Journal, this so-called cabaret tax imposed a 30% tax at venues that featured dancing to a live band and served food. Clubs that provided instrumental music with no dancing were exempt. Within 5 years, the big band sound was dead, replaced by “a new and undanceable jazz performed primarily by small instrumental groups – bebop. . ..” The cabaret tax was finally eliminated in 1965, but by then the rock-and-roll revolution was well underway.

The President’s Council of Advisors on Science and Technology (PCAST) recently issued a report to the President of the United States on propelling innovation in drug discovery, development, and evaluation [1]. It is well worth your time to read the entire report. The Council stated that the pace of new therapeutic development has not kept up with the explosion in scientific knowledge of cancer, heart disease, diabetes, and other devastating diseases. Their recommended actions have the audacious goal of doubling, over the next decade, the rate of invention of new medicines for patients, while increasing drug safety.

Here is computer scientist David Gelernter’s [1] answer to the annual question “2013 : What *Should* We Be Worried About?” at the website Edge [2].

In 2005, playwright David Mamet* wrote a memo to the writers of the TV show The Unit that went viral on the internet. I have taken some liberties to adapt the memo to pharmacometricians on drug development teams. If you read the online version of the real memo, you will see that I did not have to do much editing, save for redefining the word “drama.”

Welcome to the beginning of 2013. Most of us, I bet, had a challenging 2012, certainly it was stressful, but there is so much to be grateful for and, if one is optimistic, there are many opportunities that are full of promise for the New Year.

A New York Times* online essay by Gary Gutting, a philosophy professor, contains one of the clearest explanations of the differences between inductive and deductive reasoning I have seen.

Criminologist David M. Kennedy’s (1) strategy for reducing gang violence has dramatically reduced youth homicide rates nationwide. Dubbed the “Boston Miracle,” this strategy brings together all the key actors in a neighborhood from the police and community members to gang members, drug dealers, and their mothers and grandmothers to openly discuss their issues. Boston’s youth murders were cut by two thirds after installation of the program (2).

Being the Team Leader of an R&D team might not be down at the level of some of the jobs on Mike Rowe’s Dirty Jobs on TV’s Discovery Channel, but I nominate it as the worst job in Pharma.

Carole King, a songwriter and singer who has 4 Grammy Awards, was interviewed last spring by Terry Gross on the nightly NPR program, Fresh Air.

Scientific excellence–asking the right question, then designing and conducting a valid study that answers that question and influences future research–is widely accepted as a benchmark for success in research. However, excellence of a more complicated sort is required in Pharma research. For example, excellence in pharmacometric modeling and simulation has to encompass 3 types of excellence: strategic, operational, and technical.

Elmer Sperry (1860-1930) is remembered as the father of cybernetic (feedback control) engineering. He was the author of more than 350 patents in a wide range of fields, and he developed gyro-controlled steering and fire control systems used on Allied warships during World War I and World War II. He was among the first of the independent inventors of the early 20th century to be elected to the National Academy of Sciences (1).