{"id":"W3208200825","doi":"10.1124/dmd.121.000637","title":"In Defense of Current Concepts and Applications of Clearance in Drug Development and Therapeutics","year":2021,"lang":"en","type":"letter","venue":"Drug Metabolism and Disposition","topic":"Pharmacogenetics and Drug Metabolism","field":"Pharmacology, Toxicology and Pharmaceutics","cited_by":15,"is_retracted":false,"has_abstract":false,"ca_institutions":"University of Toronto","funders":"Medical Research Council; Natural Sciences and Engineering Research Council of Canada","keywords":"Physiologically based pharmacokinetic modelling; Metabolic clearance rate; Pharmacokinetics; Clearance; Drug; Pharmacology; Drug development; Clearance rate; Intensive care medicine; Medicine; Extrapolation; Chemistry; Mathematics; Internal medicine; Urology; Statistics","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0005439977,0.0003118052,0.0006865078,0.0003037984,0.00007221159,0.00001653256,0.0001263035,0.0003371215,0.0000310738],"category_scores_gemma":[0.000008268553,0.0003178445,0.00005350024,0.0002745479,0.0003212102,0.00009629098,0.0001210967,0.001095354,0.00000128692],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00001621538,"about_ca_system_score_gemma":0.0001103053,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00004198433,"about_ca_topic_score_gemma":0.00003559934,"domain_scores_codex":[0.997852,0.0005185253,0.0006861918,0.0004493475,0.0001888936,0.0003050261],"domain_scores_gemma":[0.999105,0.0002317904,0.0003086278,0.000162014,0.000102499,0.00009001927],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"design_other","study_design_gemma":"not_applicable","study_design_scores_codex":[0.001233954,0.002350014,0.01497602,0.007928553,0.0008193128,0.0002248853,0.04560255,0.0001553206,0.03221821,0.01877782,0.03060744,0.8451059],"study_design_scores_gemma":[0.002262565,0.000006009024,0.01221795,0.0001437052,0.0003535493,0.00001315779,0.0002020772,0.0001430814,0.02346268,0.001261307,0.95956,0.0003739084],"study_design_candidate":"not_applicable","study_design_consensus":null,"genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.7632897,0.2252855,0.00009580023,0.008999484,0.0006535656,0.0008793178,0.0003498396,0.00001144211,0.0004353558],"genre_scores_gemma":[0.8833173,0.06539083,0.0004429219,0.04913031,0.0007676831,0.0003003724,0.0003867737,0.00005437449,0.0002094308],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.9289526,"threshold_uncertainty_score":0.9999273,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.05631929325157674,"score_gpt":0.3964351982274604,"score_spread":0.3401159049758836,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}