“The use of modeling and simulation has become an important part of the landscape of drug development and regulatory decision-making in the pharmaceutical and biotechnology industry” said Dr. Grasela. Dr. Grasela was one of the first to recognize that the successful application of modeling and simulation to improve drug development decision-making must be based, in part, on the ability to reliably meet the information needs of the development team while adhering to cost, schedule, and quality constraints.
“The application of systems engineering tools and methodologies in the design and implementation of the infrastructure for model-based drug development is critical to improving the drug development process and the health care system as a whole” said Dr. Grasela. Early on, he recognized the need to develop tools to improve documentation and archiving capabilities for model building efforts and directed the development of the PERSPECTIVE Hypertext Data Analysis Mapping tool. More recently, he has been working on efforts to improve the communication of scientific workflows among scientists across organizations and, importantly, bridge this information to healthcare providers. Dr. Aziz Karim, Vice President of Clinical Pharmacology at Takeda Global Research & Development Center, said, “I am very happy that Ted has been recognized by AAPS as a Fellow of this prestigious society. I have known Ted over the last 20 years as a friend, a colleague, and a fellow scientist. He is always striving to improve drug development processes. His innovative ideas and vision are simply outstanding.”
Dr. Grasela was one of the early adopters of population pharmacokinetic analysis methodology, and his early collaborations with a number of pharmaceutical companies provided an understanding of the potential value of these methods in drug development. In more than 70 publications and 10 book chapters, Dr. Grasela has outlined the advantages of the population approach and the implications of model-based thinking for pharmacoepidemiology, pharmacoeconomics, and clinical pharmacology.
Thaddeus H. Grasela, PharmD, PhD is the President and Chief Executive Officer of Cognigen Corporation. He manages a group of more than 50 scientists and support staff whose primary mission is to provide modeling and simulation support for all stages of drug discovery, development, and commercialization. Dr. Grasela serves as a scientific and strategic consultant for project teams, spending a considerable amount of his time mentoring and coaching junior pharmacometricians. Dr. Grasela also directs the research program to continually improve the quality and productivity of Cognigen’s modeling and simulation efforts.
About Cognigen
Cognigen Corporation, a leading provider of pharmacometric and clinical pharmacology consulting services to the pharmaceutical and biotechnology industries, uses the tools of pharmacometrics, embedded in a highly developed enterprise infrastructure, to support decision-making at critical points
in drug development. Cognigen provides comprehensive pharmacometric analysis and support services, emphasizing pharmacokinetic and pharmacodynamic (PK/PD) modeling, statistical analyses, clinical trial simulations, and comprehensive regulatory reporting, focused on dose selection and justification decision support.
About AAPS
The AAPS is a professional, scientific society of more than 13,500 members employed in academia, industry, government and other research institutes worldwide. Founded in 1986, AAPS provides a dynamic international forum for the exchange of knowledge among scientists to enhance their contributions to health. AAPS offers timely scientific programs, on-going education, information resources, and opportunities for networking and professional development. To learn more about AAPS, visit http://www.aapspharmaceutica.com.
“I was brought to a dead stop, with arms outspread, clinging close to the face of the rock, unable to move hand or foot either up or down,” he wrote. “My doom appeared fixed. I must fall… But the terrible eclipse lasted only a moment, when life burst forth again with preternatural clearness. I seemed suddenly to become possessed of a new sense. The other self – the ghost of by-gone experiences, instinct, or Guardian Angel – call it what you will – came forward and assumed control. Then my trembling muscles became firm again, every rift and flaw was seen as through a microscope, and my limbs moved with a positiveness and precision with which I seemed to have nothing at all to do. Had I been borne aloft upon wings, my deliverance could not have been more complete.”
It’s those moments – when you do something you think you can’t possibly do – that you find out exactly who you are and what you are made of.
Thanks for reading. If you thought that was insightful, just wait until you see what we have cooked up for our next exciting topic. Only one way to find out – come back soon.
Due diligence is often done in haste and with an eye towards the big issues of safety and efficacy. But the devil is in the details as well, especially the details about dose selection and justification. Almost by definition, the biotech compounds will be in early stages of development. Instead of rushing to put these compounds into clinical trials as the industry is wont to do, how about a more thoughtful approach? How about systematically identifying and assessing the knowledge gaps, including the basis for dose selection, using modeling and simulation techniques. The ensuing development plan would then be designed to systematically address these gaps. This process does not have to take very long nor use many resources, but the opportunity to avoid late stage failures would be priceless (or at least the several hundreds of millions of dollars typically spent on late stage clinical trials).
Importantly, the goal of this assessment does not have to be a yes/no answer. Armed with the gaps in knowledge the result could be a plan to address the gaps with a more realistic strategy and more realistic expectations about the anticipated level of clinical and commercial success.
So what is the plan for this assessment?
The modeling and simulation tools and strategies for more reliably selecting doses and predicting the probability of success with clinical trials are available. These tools, and the skilled personnel to perform modeling and simulation, are not usually available to the biotech companies. A systematic approach to assessing knowledge gaps, however, would appeal to the scientist-within at both big and small companies. This assessment would provide an objective way of bridging the divide between discovery and development while playing to the strengths of both types of companies.
Thanks for reading. If you thought that was insightful, just wait until you see what we have cooked up for our next exciting topic. Only one way to find out – come back soon.
“Our expanded data assembly services are the result of a two-year research and development effort to better define data assembly requirements and develop improved communication strategies between scientists and programmers,” said Darcy Hitchcock, Head of Quality Informatics. “The systematic analysis of requirements and team communications led to the development and implementation of improved processes and tools which enable efficient and effective communications between scientists and programmers during the most demanding modeling and simulation projects. This in turn reduces the miscommunication of analysis and programming requirements and avoids costly delays in building analysis-ready datasets.”
“The new services are an extension of Cognigen’s long-standing expertise in real-time data assembly,” said Ted Grasela, President and CEO of Cognigen. “We routinely serve as an unblinded reviewer of PK and PD data and we have considerable experience in working with Data Safety Monitoring Boards requiring blinded exposure response information for assessing safety risks. We also provide exploratory data analysis services, which is an essential rapid prototyping exercise to assess the feasibility of a data analysis plan given the actual data collected from research sites.
Typical deliverables from Cognigen’s data assembly service include formalized requirements specifications, analysis-ready datasets, programming code, data deletion listings, and complete data definition documentation, including define.pdf files. A systematic data assessment and assembly process, governed by detailed policies and standard operating procedures, is followed and can be customized to meet client-specific needs. Documentation of program verification, data validation, and program quality control are archived and can be provided upon request.
About Cognigen.
Cognigen Corporation, a niche provider of pharmacometric and clinical pharmacology consulting services to the pharmaceutical and biotechnology industries, uses the tools of pharmacometrics, embedded in a highly developed enterprise infrastructure, to support decision-making at critical points in drug development. Cognigen provides comprehensive pharmacometric analysis and support services, emphasizing pharmacokinetic and pharmacodynamic (PK/PD) modeling, statistical analyses, clinical trial simulations, and comprehensive regulatory reporting, focused on dose selection and justification decision support.
Think this job may be for you? Send us your resume and say “hello.”
Think this job may be for you? Send us your resume and say “hello.”
Think this job may be for you? Send us your resume and say “hello.”
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.
Kerfuffles are important to pharmacometricians for three reasons. First, they waste valuable resources while generating little knowledge of real value. Second, they put pharmacometricians in the uncomfortable role of being an apologist in having to explain why modeling, under these circumstances, is not feasible and that “even allocating more money or additional resources won’t fix the immediate problem.” Third, they can pit industry against regulatory scientists because the lack of objective standards for model acceptability can reduce discussions to a subjective basis. The process of eradicating or minimizing the impact of these pharmacometric kerfuffles begins with the recognition that the errors that contribute to the kerfuffle are not just an unpleasant aspect of the job that pharmacometricians must learn to live with in the conscientious execution of their work.
Are you hooked? Don’t worry, there’s more where that came from. Check back soon for the next installment.
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