PPT-Estimating the dose-toxicity curve from completed Phase I studies

Alexia Iasonos Irina Ostrovnaya Department of Biostatistics Memorial Sloan Kettering Cancer Center CRM Workshop October 2009 Motivation Retrospective analysis of completed Phase I studies in order to recommend possibly a new MTD . View across Swiftcurrent Lake. Acute Toxicity. Recognizing, defining and measuring the effects of chemicals in organisms. “. If you want to explain each poison correctly, what is there that is not poison? All things are poison and nothing without poison. . oncology. Shu-Fang Hsu Schmitz. University of Bern, Bern, Switzerland . Phase I trials . First in human. Ever first in human, or for a specific indication, or for a specific combination . treatment, or for a specific dosing schedule. Colorado School of Public Health. January 30. th. , 2013. Table of Contents. Orientation. Introduction. Components of a Phase I Trial. Phase I Trial Designs. Rule-Based Designs. Statistical Designs. References. . Hong Li. (Acknowledgement: some slides from Rick Chappell, . Univ. of . Wisc. ). Historically, DOSE FINDING study. Determine maximal tolerated dose (MTD). Recommend dose for Phase II clinical trials. Sumathi Nambiar MD MPH. Director. Division of Anti-Infective Products. November 7, 2016. Outline. General considerations with clinical trials early in development. Predictable and unpredictable adverse reactions. Phase I Trials: Statistical Design Considerations Elizabeth Garrett-Mayer, PhD (Acknowledgement: some slides from Rick Chappell, Univ of Wisc ) Historically, DOSE FINDING study Classic Phase I objective: FOR BIS(2 - ETHYLHEXYL)ADIPATE (DEHA) Contract No. CPSC - D - 17 - 0001 Task Order No. 003 Prepared by: Risk Science Center Department of Environmental Health University of Cincinnati 160 Panzeca . Dr. N.M. ABDUL KHADER JAILANI. Objectives. . To characterize the most common toxicities of conventional chemotherapy. To describe the relationship between the mechanism of action of a chemotherapy drug and its associated toxicities. in-vivo . and . in vitro. methods. John R. Bucher, Ph.D. ., . DABT. National Institute of Environmental Health Sciences (NIEHS). National Institutes of Health. U California, Berkeley. November 4, 2016. Once a lead molecule (candidate compound) is identified, non-clinical development begins. Non-clinical studies seek to answer the following questions:. Does it work? (. E. fficacy assessment). How can it be delivered and how does the body react? . Elizabeth Garrett-Mayer, PhD. Director, Division of Biostatistics and . Research Data . Governance. Center for Research and Analytics (CENTRA). American Society of Clinical Oncology (ASCO). Alexandria, VA. B.Pharm. . Sixth Sem.. BP602T. Subacute Toxicity. Subacute toxicity studies are intended to evaluate a drug's toxic potential and pathological effects following a treatment/. repeated administration. Brenda J. Gehrke, Ph.D.. Office of New Drugs/CDER/FDA. November 2016. Abbreviations. ADME. : absorption, distribution, metabolism, excretion. HU. : hydroxyurea. IB. : Investigator Brochure. ICH. : International Council for . Acronyms used in preclinical . development. Beginners. Brief recall about clinical trials. The Funnel. Road map. Example of drug development: . . Chemical level. . Pharmaceutical level. . Preclinical pharmacology.