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Priorities for a Nonclinical Standardization Roadmap Debra Oetzman, Covance Laboratories Inc, Madison, WI; Lynda Sands, GlaxoSmithKline, King of Prussia, PA; Robert Dorsam, Food and Drug Administration, Silver Spring, MD; Gitte Frausing, Novo Nordisk, Denmark; Rick Thompson, Janssen Research & Development, Raritan, NJ; Anisa Scott, JMP Life Sciences, SAS Institute, Cary, NC; Lou Ann Kramer, Eli Lilly and Company, Indianapolis, Indiana; Sarah Obbers, Janssen Research & Development, Beerse, Belgium. Disclaimer: The opinions expressed on this poster are those of the authors and do not necessarily represent those of their organizations. High Medium Low Study Group Priority Prioritization of Study Groups. Study groups are listed in order of their priority based on the results of the survey. Single asterisks (*) indicate study groups which have been standardized. Double asterisks (**) represent those study groups currently being standardized. Introduction The Standards Roadmap Team (a subset of the FDA / PhUSE Working Group 6) have forged a collaboration aimed at addressing common issues with data management, data standards, and standards implementation. To support this activity, the group created a survey for members of industry to further understand the priorities of the many stakeholders of nonclinical data. We asked them to consider the entire expanse of nonclinical studies listed for Module 4 of the eCTD. Responders rated the study types and data elements with a scale of high, medium, or low priority and also had the option of leaving it blank (indicating no particular preference). the respondents were provided with a text field where they could provide a rationale for their response. A spot to comment on rationale for the preference was provided, and responders were asked to indicate whether they were responding as an individual or on behalf of their organization. Respondents consisted of both companies/institutions (n=4) and individuals (n=11) throughout industry. Study Type Priority Data Elements Priority High High Carcinogenicity General Toxicology Developmental and Reproductive Toxicology High Historical Control Data Medium Study Design and logistics Safety Pharmacology Low Clinical Signs Formulation Data (Lot/Study linkages Safety Pharmacology High Respiratory Safety Pharm. Biomarker incorporation Medium Cardiovascular Safety Pharm. Medium Low CNS Safety Pharm. Renal/Urinary System Autonomic Nervous System Gastrointestinal System Metadata/context , (Connectivity across data, documentation of study design, tool development, etc) Sample/specimen descriptions, ex vivo study Study Tags (pharm class, etc) Pharmacodynamic Drug Int. Elements of Interconnectivity Other studies Cell line descriptions (i.e. for in vitro studies) 0 2 4 6 8 Priority (# responses per priority level) 10 12 14 Device combinations Pharmacokinetics Image data (e.g. X-ray of NHP bone develop.) Medium Low Low Medium In vivo efficacy studies for FDA's Animal Rule High Pharmacokinetics (PK) Metabolism PK Drug Interactions Distribution Other Nonclinical Topics / Data Elements 0 2 4 6 8 10 12 14 Priority (# responses per priority level) Absorption Analytical Method/Valid. Report Excretion Other Pharmacokinetic Studies 0 2 4 6 8 10 12 14 High Priority (# responses per priority level) Genetic Toxicology Miscellaneous High Immunotoxicity High Medium Medium Receptor Screens Low Low Mechanistic studies (if not elsewhere) Medium Low Genotoxicity (in vivo) Genotoxicity (in vitro) Bacterial Reverse Mutation Assay (Ames) Mammalian Cell Micronucleus Test In Vivo Comet Assay Mammalian Chromosome Aber. Test Mamm. Erythrocyte Micronucleus Test E. coli Reverse Mutation Assay Mamm. Bone Marrow Chrom. Aber. Test Mammalian Cell Gene Mutation Test Sister Chrom. Exchange Assay in Mamm. Tg. Rodent Som. & Germ Cell Gen Mut Liver Unsched. DNA Synthesis 0 2 4 6 8 10 Priority (# responses per priority level) 12 14 Metabolites Local Tolerance Impurities Antigenicity Pharmacology Dependence Mitogenicity Medium Primary Pharmacodynamics Low Secondary Pharmacodynamics Low High Pharmacology Studies Other Toxicity Studies (if available) 0 0 2 4 6 8 10 12 14 1 2 3 4 5 6 7 8 Priority (# responses per priority level) 9 10 Priority (# responses per priority level) Prioritization of Study Types. Individual study types were rated as high, medium, or low priority by survey respondents. Red Font indicates study groups that have been standardized. Blue font denotes study types that are currently being standardized. Summary The results of the survey indicated that carcinogenicity and general toxicology were the highest priority study groups. Next, developmental and reproductive toxicology (DART) and safety pharmacology were high priorities. DART studies (Segment I, II, III) were similar in their perceived priority, whereas safety pharmacology had both high and low priorities among their study types. Pharmacokinetics studies were medium priority along with genetic toxicology studies. Respondents differed on the utility of pharmacology studies, which received both high and low priority status. A prioritization of several data elements which can be applied across study types is also provided. The Roadmap team recognized value in keeping study types grouped since conventions of standardization may be applied to several study types within a study group. Data utility, accessibility, gaps and complexity along with metadata linkage, resources, timelines and technological advancements in collection and/or reporting systems should be considered and carefully integrated as the roadmap is created. As we continue our work, the Team will use the data collected and presented in this poster to suggest a roadmap for development of nonclinical standards. Contact the Nonclinical Standardization Roadmap Working Group if you are interested in participating in this group at this link: http://www.phusewiki.org/wiki/index.php?title=WG6_Nonclinical__Standardization_Roadmap or responding to the survey at this link: http://www.phusewiki.org/wiki/index.php?title=File:Roadmap_Prioritization_PDF_V10.pdf.