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Day one Wednesday 29th October
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8.30am | Registration & coffee
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9am | Opening remarks from the chair
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| | Dr Alain Mignot, Senior Consultant Early Clinical Development, SGS Life Sciences
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9.15am | Keynote presentation: Cardiac Safety Research Consortium: building a collaborative environment based on the principles of the Critical Path Initiative
• The challenge of identifying cardiac safety issues
• The mission of the FDA's Critical Path Program
• The Cardiac Safety Research Consortium (CSRC) Duke-FDA public-private partnership construct
• Initial directions of the CSRC: from QTc and beyond
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| NON CLINICAL SAFETY PHARMACOLOGY |
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9.45am | S7B guidelines: impact on preclinical testing – a regulators perspective
• What do these guidelines mean?
• Timing of safety pharmacology studies
• Core battery safety pharmacology studies
• What it means - follow-up studies
• Case studies based on ICH S 7B guidelines
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| | Dr Klaus Olejniczak, Head of Genetic and Reproduction Toxicology Unit, Federal Institute for Drugs and Medical Devices (BfArM)
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10.15am | S7B guidelines: impact on preclinical testing – an industry perspective
• Requirements for preclinical safety testing according to S7B
• Which test systems at which time points
• Practical approaches in a mid sized pharmaceutical company
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10.45am | Preclinical safety testing strategies
• Cardiovascular safety pharmacology testing as well as cardiac (QT) issues, following S7A and S7B guidelines |
| | Dr Gary Gintant, Senior Group Leader, Integrative Pharmacology, Abbot Laboratories
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11.15am | Morning tea
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11.45am | Preclinical proarrhythmic models encompassing predisposing factors: implications for drug safety testing
• Ex-vivo and in-vivo proarrhythmic models in which electrophysiological biomarkers other than QT prolongation have been evaluated for their ability to predict TdP in man.
• Merits and shortcomings
• Relevance in human studies
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| | Dr Danshi Li, Medical Safety Assessment, Global Pharmaciovigilance and Epidemiology, Bristol-Myers Squibb Pharmaceutical Research Institute
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12.15pm | Promising in-vitro approaches in cardiac safety testing
• The limits of available tools
• A new promising assay providing electrophysiological signature for TdP drugs
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12.45pm | Lunch
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| BIOLOGICS CASE STUDIES |
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1.45pm | Case study: preclinical testing of biologic compounds
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2.15pm | Cardiovascular safety strategies for biopharmaceuticals
• Regulatory background
• Proposed cardiovascular testing strategy
• Rationale to not use the hERG assay
• Case studies
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2.45pm | Speed networking
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3.30pm | Afternoon tea
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| CLINICAL QT ASSESSMENT |
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4pm | ICH E14 guidelines: experience from the ICH E14 implementation working group and submission review
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4.30pm | Design considerations for a TQT study
• Why “proving” the absence of an effect that might predict harm is quite difficult
• The consequences of considering progressively smaller differences as potentially predictive of harm
• Design alternatives that may improve on the ability of a TQTS to “prove” the absence of an effect that might predict harm
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5pm | Closing remarks from the chair
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5.15pm | Networking reception
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Day two Thursday 30 October
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9am | Registration & coffee
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9.30am | Opening remarks from the chair
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9.45am | Reduction of size and cost of detailed clinical QT studies
• Implications of QTc precision of power sample calculations of QTc studies
• Principal possibilities of cost reduction
• Intelligent combinations of fully automatic and manual measurements
• Examples of reducing costs while maintaining data quality and study outcome
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10.15am | Drug induced QT / QTc prolongation – review of one-stage vs. two-stage methods to analyse clinical ECG data
• One-stage vs. two-stage methods to analyse clinical ECG data
• Assumptions of different methods
• False positive rate among different methods
• Selection of appropriate method to analyse clinical ECG data
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10.45am | ICH E14 and statistics: design and analysis
• Standard ways to analyse a TQT study
• Designing for efficient use of measurements obtained from each subject
• Assay sensitivity and why the FDA does not follow the guidance
• Statistics after a positive TQT study
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| | Dr Georg Ferber, Group Head Biostatistics, Cardiovascular, Novartis Pharma AG
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11.15am | Morning tea
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11.45am | Statistical issues in the exposure-response analysis of the QTc intervals
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| | Dr Arne Ring, Phase I - Iia Statistics, Boehringer Ingelheim Pharma GmbH
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12.15pm | Electrocardiography clinical safety evaluation
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12.45pm | Lunch
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1.45pm | Panel discussion: can QT studies accurately assess proarrythmia risk?
As pharmaceutical products become more complex, do current regulatory guidelines enable the industry to accurately predict risk of proarrhythmia? Hear the latest thinking in this critical area.
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2.15pm | Late stage development – implications on QT assessment
• Drug development when the Thorough QT Study is positive
• Rational approaches to further QT assessment
• Safety analysis during later stages of development
• Efficiency of evaluation, PK/PD modeling
• Innovative study designs will be discussed along
• Possible reasons for a “false-positive” QT study
• Labeling considerations and approaches will be explored
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2.45pm | Case study: QT assessment in oncological products
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3.15pm | Recent Experience with probabilistic QT heart rate corrections in man
• Historical perspective vs. the current state-of-the art
• QT rate-corrections: assumptions, accuracy, and predictive value
• Preclinical and clinical QT studies - contrasting methodologies
• Diurnal changes in the QT interval: impact on QT rate-corrections
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3.45pm | Closing remarks from the chair
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4pm | Tea and end of conference
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