Monday, September 20, 2010
AM Courses: 8:00 AM–12:00 NOON
PM Courses: 2:00 PM–6:00 PM
AM1: Safety Pharmacology: Introduction, Application, and Interpretation
Course Chairs: Tom Beck and Jay Gizzi
Safety pharmacology is a relatively new and rapidly growing discipline. The primary regulatory documents governing safety pharmacology is the ICH Harmonised Tripartite Guidelines S7A and S7B. The stated goal of these documents is “To help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals”. These ICH documents serve as guidelines and provide recommendations regarding the approach to evaluate therapeutics with respect to core organ systems (cardiovascular, respiratory and central nervous systems), supplemental organ systems (e.g., GI and renal) and follow-up studies to describe effects and mechanisms of action. The objective of this course is to provide an overview of safety pharmacology, current regulations and how they relate to drug development. This course is a broad overview of the common test systems and is therefore a good prerequisite to the more advanced continuing education courses offered. The course will include presentations from principal scientists with emphasis on the regulatory environment and the current state-of-the-art methodologies specific to each of the core battery and supplemental organ systems assays. These didactic presentations will be followed by a presentation and group discussions on integrated risk assessment in safety pharmacology.
AM2: Intermediate Cardiovascular
Course Chairs: Dusty Sarazan and Blake Anson
This Intermediate Cardiovascular course is intended for individuals with previous knowledge of cardiovascular safety pharmacology as well as those interested in learning more about cardiovascular safety studies. This is an “everything you want to know about cardiovascular system” course. With an over-arching leaning toward safety pharmacology applications, lectures covered in this course will include overviews of electrophysiology, electrocardiography, cardiovascular physiology-contractility, hemodynamics, the utility of stem cell technologies, and non-invasive measurements of cardiac function. Active participation from the attendees is highly encouraged.
AM3: Safety Pharmacology Study Design and Data Analysis
Course Chairs: George Thomas and Henry Holzgrefe
Have you wondered about the right design for a Safety Pharmacology study? Is randomized Latin square design better than dose increment design in a telemetry study? Should I have male and female rats in my Irwin study? My data show statistical significance, but is it really a biologically relevant adverse effect? Should I use rats or guinea-pigs for my respiratory study? Which is the best QTc correction formula for telemetry monkey studies?
This course is designed to provide an overview of regulatory safety pharmacology study designs and analysis for NCEs and biologics. Basic questions arising from the practice of Safety Pharmacology will be addressed. The course will examine various study designs commonly utilized for ICH S7A- and S7B- guided studies such as Modified Irwin, Cardiovascular Telemetry, Pulmonary Function and hERG. Topics discussed will include appropriate test systems, different dosing paradigms, data analysis techniques, QT correction and importance of biological relevance. Specific questions/suggestions/cases from participants will be addressed/discussed during the last 30 minutes of the course.
AM4: Intermediate Central Nervous System Safety Pharmacology
Course Chairs: Wael Mohamed and Greet Teuns
Animal models are essential to understand human disorders. In fact, in animals we can administer drugs in different doses and monitor the possible adverse effects and safety margins. For instance, using the rodent models has enabled us to identify some of the neurological changes underlying behavioral aspects of Attention Deficit Hyperactivity Disorder (ADHD). There are several animal models for studying ADHD, each of them has pros and cons; for example, some of these models have decreased in the extra-cellular dopamine (DA) concentration, while DA concentration has been increased in other models. Therefore, it is essential to study animal models to fully understand the neuropathology of ADHD. Moreover, using such animal models is useful in testing new compounds which might be useful in the alleviation of ADHD signs and symptoms.
Given the complex and diverse functions of the central nervous system, this course is designed to describe the validity of the different animal models used to study ADHD. This is followed by the use of multidisciplinary approaches including neurobiological, neurophysiological, neuropathological, and/or behavior techniques that is used. Examples of other models used to assess the potential for adverse neurological effects such as learning and memory deficits, seizure potential, abuse liability, and more will be discussed.
This course will explore some of the more advanced behavioral and electrophysiological techniques available for evaluation of key nervous system functions that are not adequately addressed by the animal models. These include assessment of abuse potential, EEG, net station and brain vision analyzer.
PM5: Pharmacokinetics/Dried Blood Spot Technologies
Course Chairs: Brad Main, Lew Kinter, Chris Evans
Pharmacokinetic principles and technologies characterize and quantify exposure to parent drug and metabolites in preclinical studies (including Safety Pharmacology) and in clinical trials. Safety pharmacology studies are best interpreted, and potential drug effects on organ system functions mitigated in terms of assessment of human risk thru comparative pharmacokinetics. However, while associations of drug-induced changes in organ functions and exposures in safety pharmacology studies are best accomplished when these measurements are collected coincidently in the same animals, the blood collection procedures and necessary blood volumes have necessitated used of separate satellite groups or reliance on pharmacokinetic/toxicokinetic assessments in separate studies, especially when using small animals. Recent advances in microsampling and microanalysis technologies now permit safety pharmacology and pharmacokinetic endpoints in the same study animals without compromise, affording opportunities to improve study data quality, reduce animal study numbers (Refinement and Reduction improvements), and to identify biomarkers with which to mitigate risk in human clinical trials. This course will deliver general principles and technologies of modern pharmacokinetic sampling, data acquisition, manipulation and interpretation, and current status of microsampling/dried blood spot technologies for safety pharmacologists.
PM6: Safety Pharmacology in Early Drug Evaluation and Development. How Can Frontloading Save Time and Money?
Course Chairs: Mary Jeanne Kallman and Pierre Morissette
This course examines the practice and philosophy of conducting studies designed to illuminate safety risk earlier in the drug development process (frontloading). Frontloading can be defined as those safety assessments conducted during lead optimization of compounds before selection as a candidate drug for development and before regulatory studies are performed. The goal of early safety assessment or frontloading is to provide quality safety data that can drive development decisions much earlier in the flow scheme. Such studies also save resources by reducing late stage attrition.
The course will examine what methods and processes have been successfully applied at reducing attrition and to provide "no surprises" approach to later stage GLP safety studies. Various practices and philosophy will be discussed by the speakers with adequate time for class discussion.
PM7: Drug Abuse Liability Testing
Course Chairs: Greet Teuns and Donald Hodges
Drug abuse liability testing has become a hot topic in drug development and in particular, within the nonclinical safety evaluation arena since the release of the EMEA guideline (March 2006), the ICH guideline (June 2009) and most recent FDA draft guidance (January 2010).
This course is meant to discuss the various topics within this field:
- The pathways responsible for development of potential abuse will be introduced to gain more understanding at the molecular level.
- The different aspects of drug abuse (physical dependence, conditioning and rewarding, reinforcing properties) and the various methods to investigate each of these dimensions will be discussed in detail. The impact of the GLP requirements as stated within the guidelines will also be assessed.
- For new molecular entities (NMEs) with novel mechanisms of action: what is a complete and robust nonclinical package on drug abuse potential for these compounds? What are possible variables in the test designs or within the package itself that might contribute to the identification of drug abuse potential if modified on a scientific basis?
Lastly the translational approach will be taken into account. What’s the predictability of a preclinical package for drug abuse potential for NMEs in development and how will the next steps towards clinical evaluation be set?
PM8: Electrocardiography (ECG) Waves; Reading and Interpretation
Course Chairs: Alfred Botchway and Tiffini Brabham
A decade on from the formation of the Safety Pharmacology Society, scientist in the field across the world continue to have to review ECGs as an essential tool to the assessment of effects on the heart. Abnormalities such as arrhythmias, myocardial infarctions, atrial enlargements, ventricular hypertrophies, and bundle branch blocks can be discerned on an ECG. This course will be taught by world leaders in the fields of safety pharmacology and electrophysiology. This CE course is designed to help students, technicians and other allied health personnel acquire the skills to analyze and interpret fundamental changes in ECG morphology and identify common waveform abnormalities. The course will be a combined lecture & workshop, covering topics such as basic electrocardiography including a qualitative and quantitative assessment of the ECG waveforms.
By the end of the day, attendees are expected to be able to:
- Identify the components of a normal ECG
- Recognize common abnormalities
- Perform quantitative measurement of ECG intervals
Sample ECGs will be provided and, following practical, hands on instruction, attendees will be expected to read and interpret a test set. The intent of this course is as an interactive facilitated discussion. The course instructors will present scenarios and facilitate the discussion with course participants. Course participants are encouraged to submit sample ECGs (3 PowerPoint slides) to the session Chair prior to the meeting to allow broader experiences for the discussion.
Participation in the CE course, Intermediate Cardiovascular Safety Pharmacology, is strongly recommended prior to attending this class.