{"id":"https://openalex.org/W2036065701","doi":"https://doi.org/10.1007/s00204-014-1335-2","title":"Optimal experimental designs for dose\u2013response studies with continuous endpoints","display_name":"Optimal experimental designs for dose\u2013response studies with continuous endpoints","publication_year":2014,"publication_date":"2014-08-25","ids":{"openalex":"https://openalex.org/W2036065701","doi":"https://doi.org/10.1007/s00204-014-1335-2","mag":"2036065701","pmid":"https://pubmed.ncbi.nlm.nih.gov/25155192","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/4655015"},"language":"en","primary_location":{"id":"doi:10.1007/s00204-014-1335-2","doi":"https://doi.org/10.1007/s00204-014-1335-2","is_oa":true,"landing_page_url":"https://doi.org/10.1007/s00204-014-1335-2","pdf_url":"https://link.springer.com/content/pdf/10.1007/s00204-014-1335-2.pdf","source":{"id":"https://openalex.org/S87018847","display_name":"Archives of Toxicology","issn_l":"0340-5761","issn":["0340-5761","1432-0738"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319900","host_organization_name":"Springer Science+Business Media","host_organization_lineage":["https://openalex.org/P4310319900","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Springer Science+Business Media","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Archives of Toxicology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://link.springer.com/content/pdf/10.1007/s00204-014-1335-2.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5050943602","display_name":"Tim Holland\u2010Letz","orcid":"https://orcid.org/0000-0003-0348-8163","observed_orcids":["https://orcid.org/0000-0003-0348-8163"]},"institutions":[{"id":"https://openalex.org/I17937529","display_name":"German Cancer Research Center","ror":"https://ror.org/04cdgtt98","country_code":"DE","type":"facility","lineage":["https://openalex.org/I1305996414","https://openalex.org/I17937529"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Tim Holland-Letz","raw_affiliation_strings":["Biostatistics Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. t.holland-letz@dkfz.de","German cancer Research Center (DKFZ);"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biostatistics Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. t.holland-letz@dkfz.de","institution_ids":["https://openalex.org/I17937529"]},{"raw_affiliation_string":"German cancer Research Center (DKFZ);","institution_ids":["https://openalex.org/I17937529"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5075067956","display_name":"Annette Kopp\u2010Schneider","orcid":"https://orcid.org/0000-0002-1810-0267","observed_orcids":["https://orcid.org/0000-0002-1810-0267"]},"institutions":[{"id":"https://openalex.org/I17937529","display_name":"German Cancer Research Center","ror":"https://ror.org/04cdgtt98","country_code":"DE","type":"facility","lineage":["https://openalex.org/I1305996414","https://openalex.org/I17937529"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Annette Kopp-Schneider","raw_affiliation_strings":["Biostatistics Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany","German cancer Research Center (DKFZ);"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biostatistics Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany","institution_ids":["https://openalex.org/I17937529"]},{"raw_affiliation_string":"German cancer Research Center (DKFZ);","institution_ids":["https://openalex.org/I17937529"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5050943602"],"corresponding_institution_ids":["https://openalex.org/I17937529"],"apc_list":{"value":5690,"currency":"USD","value_usd":5690},"apc_paid":{"value":5690,"currency":"USD","value_usd":5690},"fwci":1.2587,"has_fulltext":true,"cited_by_count":47,"citation_normalized_percentile":{"value":0.8290788,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"89","issue":"11","first_page":"2059","last_page":"2068"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11798","display_name":"Optimal Experimental Design Methods","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/1803","display_name":"Management Science and Operations Research"},"field":{"id":"https://openalex.org/fields/18","display_name":"Decision Sciences"},"domain":{"id":"https://openalex.org/domains/2","display_name":"Social Sciences"}},"topics":[{"id":"https://openalex.org/T11798","display_name":"Optimal Experimental Design Methods","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/1803","display_name":"Management Science and Operations Research"},"field":{"id":"https://openalex.org/fields/18","display_name":"Decision Sciences"},"domain":{"id":"https://openalex.org/domains/2","display_name":"Social Sciences"}},{"id":"https://openalex.org/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.0015999999595806003,"subfield":{"id":"https://openalex.org/subfields/2613","display_name":"Statistics and Probability"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10243","display_name":"Statistical Methods and Bayesian Inference","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2613","display_name":"Statistics and Probability"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/optimal-experimental-design","display_name":"optimal experimental design","score":0.9599999785423279},{"id":"https://openalex.org/keywords/dose-response-studies","display_name":"dose-response studies","score":0.9599999785423279},{"id":"https://openalex.org/keywords/d-optimal-design","display_name":"D-optimal design","score":0.8289999961853027},{"id":"https://openalex.org/keywords/sample-allocation","display_name":"sample allocation","score":0.7639999985694885},{"id":"https://openalex.org/keywords/dose-levels","display_name":"dose levels","score":0.8429999947547913},{"id":"https://openalex.org/keywords/weibull-function","display_name":"Weibull function","score":0.9679999947547913},{"id":"https://openalex.org/keywords/toxicology","display_name":"toxicology","score":0.6510000228881836},{"id":"https://openalex.org/keywords/cytotoxicity","display_name":"cytotoxicity","score":0.7319999933242798},{"id":"https://openalex.org/keywords/96-well-plate-assay","display_name":"96-well plate assay","score":0.7940000295639038},{"id":"https://openalex.org/keywords/parameter-misspecification","display_name":"parameter misspecification","score":0.7889999747276306},{"id":"https://openalex.org/keywords/efficiency-loss","display_name":"efficiency loss","score":0.7739999890327454}],"concepts":[{"id":"https://openalex.org/C186394612","wikidata":"https://www.wikidata.org/wiki/Q7098942","display_name":"Optimal design","level":2,"score":0.7153315544128418},{"id":"https://openalex.org/C129848803","wikidata":"https://www.wikidata.org/wiki/Q2564360","display_name":"Sample size determination","level":2,"score":0.6732541918754578},{"id":"https://openalex.org/C34559072","wikidata":"https://www.wikidata.org/wiki/Q2334061","display_name":"Design of experiments","level":2,"score":0.5768799781799316},{"id":"https://openalex.org/C173291955","wikidata":"https://www.wikidata.org/wiki/Q732332","display_name":"Weibull distribution","level":2,"score":0.5121784210205078},{"id":"https://openalex.org/C207201462","wikidata":"https://www.wikidata.org/wiki/Q182505","display_name":"Bayes' theorem","level":3,"score":0.4838503897190094},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4688830077648163},{"id":"https://openalex.org/C126255220","wikidata":"https://www.wikidata.org/wiki/Q141495","display_name":"Mathematical optimization","level":1,"score":0.46541428565979004},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.4448874294757843},{"id":"https://openalex.org/C2780615836","wikidata":"https://www.wikidata.org/wiki/Q2471869","display_name":"USable","level":2,"score":0.4254019558429718},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.3604552149772644},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.34809744358062744},{"id":"https://openalex.org/C200601418","wikidata":"https://www.wikidata.org/wiki/Q2193887","display_name":"Reliability engineering","level":1,"score":0.33597439527511597},{"id":"https://openalex.org/C107673813","wikidata":"https://www.wikidata.org/wiki/Q812534","display_name":"Bayesian probability","level":2,"score":0.2807634770870209},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.1360376477241516},{"id":"https://openalex.org/C136764020","wikidata":"https://www.wikidata.org/wiki/Q466","display_name":"World Wide Web","level":1,"score":0.0},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0},{"id":"https://openalex.org/C78458016","wikidata":"https://www.wikidata.org/wiki/Q840400","display_name":"Evolutionary biology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008962","descriptor_name":"Models, Theoretical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D012107","descriptor_name":"Research Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014116","descriptor_name":"Toxicology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D018401","descriptor_name":"Sample Size","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018675","descriptor_name":"Toxicity Tests","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D023381","descriptor_name":"Endpoint Determination","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1007/s00204-014-1335-2","doi":"https://doi.org/10.1007/s00204-014-1335-2","is_oa":true,"landing_page_url":"https://doi.org/10.1007/s00204-014-1335-2","pdf_url":"https://link.springer.com/content/pdf/10.1007/s00204-014-1335-2.pdf","source":{"id":"https://openalex.org/S87018847","display_name":"Archives of Toxicology","issn_l":"0340-5761","issn":["0340-5761","1432-0738"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319900","host_organization_name":"Springer Science+Business Media","host_organization_lineage":["https://openalex.org/P4310319900","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Springer Science+Business Media","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Archives of Toxicology","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:4655015","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4655015","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Arch Toxicol","raw_type":"Text"},{"id":"pmid:25155192","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/25155192","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Archives of toxicology","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1007/s00204-014-1335-2","doi":"https://doi.org/10.1007/s00204-014-1335-2","is_oa":true,"landing_page_url":"https://doi.org/10.1007/s00204-014-1335-2","pdf_url":"https://link.springer.com/content/pdf/10.1007/s00204-014-1335-2.pdf","source":{"id":"https://openalex.org/S87018847","display_name":"Archives of Toxicology","issn_l":"0340-5761","issn":["0340-5761","1432-0738"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319900","host_organization_name":"Springer Science+Business Media","host_organization_lineage":["https://openalex.org/P4310319900","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Springer Science+Business Media","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Archives of Toxicology","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2036065701.pdf","grobid_xml":"https://content.openalex.org/works/W2036065701.grobid-xml"},"referenced_works_count":20,"referenced_works":["https://openalex.org/W1583562684","https://openalex.org/W1975316614","https://openalex.org/W1982772150","https://openalex.org/W1999372955","https://openalex.org/W2006062316","https://openalex.org/W2014018052","https://openalex.org/W2017351261","https://openalex.org/W2048144055","https://openalex.org/W2053792242","https://openalex.org/W2072361960","https://openalex.org/W2082382318","https://openalex.org/W2087361033","https://openalex.org/W2115184325","https://openalex.org/W2141780326","https://openalex.org/W2144578442","https://openalex.org/W2161886188","https://openalex.org/W2169186250","https://openalex.org/W2798510847","https://openalex.org/W3103871524","https://openalex.org/W4285719527"],"related_works":["https://openalex.org/W7134943708","https://openalex.org/W2185101500","https://openalex.org/W2103861636","https://openalex.org/W1486550552","https://openalex.org/W4389948171","https://openalex.org/W3109596955","https://openalex.org/W6925236529","https://openalex.org/W1935995916","https://openalex.org/W2743523911","https://openalex.org/W2404388595"],"abstract_inverted_index":{"In":[0],"most":[1],"areas":[2],"of":[3,26,32,42,50,59,76,91,101,114,122,133,141,161,206,220,230],"clinical":[4],"and":[5,15,20,40,94,144,170,188,241],"preclinical":[6],"research,":[7],"the":[8,13,38,48,74,89,98,102,105,111,115,131,159,203,213,221,234,248],"required":[9,92],"sample":[10,23,51],"size":[11,24,52],"determines":[12],"costs":[14],"effort":[16],"for":[17,155,209,236],"any":[18],"project,":[19],"thus,":[21],"optimizing":[22],"is":[25,35,108,226],"primary":[27],"importance.":[28],"An":[29],"experimental":[30,57,77,153],"design":[31,58,70,136,215,237],"dose-response":[33,156,164,222],"studies":[34,61,157,208],"determined":[36],"by":[37,66],"number":[39,90],"choice":[41],"dose":[43,186],"levels":[44,187],"as":[45,47,202],"well":[46,109],"allocation":[49],"to":[53,63,96,148,198],"each":[54],"level.":[55],"The":[56,128,177,193],"toxicological":[60],"tends":[62],"be":[64],"motivated":[65],"convention.":[67],"Statistical":[68],"optimal":[69,135,194,214,244],"theory,":[71],"however,":[72],"allows":[73],"setting":[75],"conditions":[78],"(dose":[79],"levels,":[80],"measurement":[81],"times,":[82],"etc.)":[83],"in":[84,125,166],"a":[85,139],"way":[86],"which":[87],"minimizes":[88],"measurements":[93],"subjects":[95],"obtain":[97],"desired":[99],"precision":[100],"results.":[103],"While":[104],"general":[106],"theory":[107,137],"established,":[110],"mathematical":[112,142],"complexity":[113],"problem":[116],"so":[117],"far":[118],"prevents":[119],"widespread":[120],"use":[121],"these":[123,146],"techniques":[124],"practical":[126],"studies.":[127],"paper":[129],"explains":[130],"concepts":[132,147],"statistical":[134],"with":[138,173],"minimum":[140],"terminology":[143],"uses":[145],"generate":[149],"concrete":[150],"usable":[151],"D-optimal":[152],"designs":[154,179,195,200,245],"on":[158,217],"basis":[160],"three":[162,185],"common":[163],"functions":[165,172],"toxicology:":[167],"log-logistic,":[168],"log-normal":[169],"Weibull":[171],"four":[174],"parameters":[175,235],"each.":[176],"resulting":[178],"usually":[180],"require":[181],"control":[182],"plus":[183],"only":[184],"are":[189,196,239],"quite":[190],"intuitively":[191],"plausible.":[192],"compared":[197],"traditional":[199],"such":[201],"typical":[204],"setup":[205],"cytotoxicity":[207],"96-well":[210],"plates.":[211],"As":[212],"depends":[216],"prior":[218],"estimates":[219],"function":[223],"parameters,":[224],"it":[225],"shown":[227],"what":[228],"loss":[229],"efficiency":[231],"occurs":[232],"if":[233],"determination":[238],"misspecified,":[240],"how":[242],"Bayes":[243],"can":[246],"improve":[247],"situation.":[249]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":8},{"year":2023,"cited_by_count":6},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":6},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":7},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":2},{"year":2012,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}