Simulations Plus

Taking fit-for-purpose (F4P) models to the next level – Collaboration between scientists and software designers

Walt Woltosz, chairman of Simulations Plus Inc., commented on the passing of world-famous astrophysicist, Professor Sir Stephen Hawking...
"Stephen Hawking was a remarkable man and a global scientific leader. But he was also charming and witty, with a nice sense of humor. He would "dance" in his electric wheelchair at festive events, spinning in circles and dazzling all who watched. He made his place in history, along with Newton, Einstein, Bohr, and so many others. He will be missed."

Envisioned by Cognigen Corporation, a Simulations Plus (Nasdaq:SLP) company, in 2003, the Pharma of the FutureSM (PoF) program was conceived as a research and training initiative to design and implement the workflows and computer systems required to support modeling and simulation (M&S) activities.

Prior to 1978, PK data was obtained from drugs that were tested on healthy young volunteers (typically medical students).

The central focus of MBR&D is not the mathematical equations but rather the conceptual synthesis process that integrates all available information and rational extrapolations to better understand drug pharmacology in the context of the disease process.

Speed and agility is more important than ever as the demand for M&S increases. KIWI 1.5 allows you to easily select and compare parameters estimates and diagnostic plots across multiple candidate models in one view to make decisions quickly and confidently, and delivers high quality graphs to inform team decision making and put in regulatory documents- all formatted, all validated!

The EMA and FDA recommend including a run record in your technical report to describe any major decisions and should include an overview of the steps taken during model development. KIWI 1.3, available in May 2015, will reduce the time taken to perform this task to just minutes.

Developing a disease drug model is an intensely creative and collaborative effort. It requires the ability to assemble available knowledge and data and to gain a collective appreciation of important relationships. As this collaborative synthesis gets underway, pharmacometricians are charged with translating the ideas and hypotheses about diseases biology and drug pharmacology into mathematical equations. The equations are then coded into the control streams that, along with the data, become the basis for investigating the feasibility of various hypotheses.

Over the years, our relationships with clients have deepened and Cognigen is often asked to begin working on projects at the earliest stages of development and to continue to refine a model as new data arrives from ongoing clinical development programs. Consequently, if a assets continues to show promise, we have the opportunity to provide modeling and simulation results at decision-making milestones over the lifecycle of clinical development. Typically, these activities culminate in a comprehensive synthesis of exposure-response relationships for efficacy and safety endpoints that are included in the regulatory submission.

View our milestones.

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].