{"id":"https://openalex.org/W7221102297","doi":"https://doi.org/10.3389/fmed.2026.1931144","title":"Clinical challenges in vaccine and monoclonal antibody development against ESCAPE pathogens: insights from EMA scientific advice procedures","display_name":"Clinical challenges in vaccine and monoclonal antibody development against ESCAPE pathogens: insights from EMA scientific advice procedures","publication_year":2026,"publication_date":"2026-10-09","ids":{"openalex":"https://openalex.org/W7221102297","doi":"https://doi.org/10.3389/fmed.2026.1931144","pmid":"https://pubmed.ncbi.nlm.nih.gov/42921014","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13692650"},"language":"en","primary_location":{"id":"doi:10.3389/fmed.2026.1931144","doi":"https://doi.org/10.3389/fmed.2026.1931144","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fmed.2026.1931144","pdf_url":"https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1931144/pdf","source":{"id":"https://openalex.org/S2597052008","display_name":"Frontiers in Medicine","issn_l":"2296-858X","issn":["2296-858X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-70","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Medicine","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1931144/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5045608423","display_name":"Igor Stojkov","orcid":"https://orcid.org/0000-0001-6788-7986","observed_orcids":["https://orcid.org/0000-0001-6788-7986"]},"institutions":[{"id":"https://openalex.org/I884002606","display_name":"Paul Ehrlich Institut","ror":"https://ror.org/00yssnc44","country_code":"DE","type":"facility","lineage":["https://openalex.org/I884002606"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Igor Stojkov","raw_affiliation_strings":["Section Data Science and Methods, Paul-Ehrlich-Institut"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Section Data Science and Methods, Paul-Ehrlich-Institut","institution_ids":["https://openalex.org/I884002606"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031536442","display_name":"Linda Marchioro","orcid":"https://orcid.org/0000-0003-4176-0252","observed_orcids":["https://orcid.org/0000-0003-4176-0252"]},"institutions":[{"id":"https://openalex.org/I884002606","display_name":"Paul Ehrlich Institut","ror":"https://ror.org/00yssnc44","country_code":"DE","type":"facility","lineage":["https://openalex.org/I884002606"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Linda Marchioro","raw_affiliation_strings":["Section Data Science and Methods, Paul-Ehrlich-Institut"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Section Data Science and Methods, Paul-Ehrlich-Institut","institution_ids":["https://openalex.org/I884002606"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047458567","display_name":"Isabelle Bekeredjian\u2010Ding","orcid":"https://orcid.org/0000-0001-6646-5888","observed_orcids":["https://orcid.org/0000-0001-6646-5888"]},"institutions":[{"id":"https://openalex.org/I161103922","display_name":"Philipps University of Marburg","ror":"https://ror.org/01rdrb571","country_code":"DE","type":"education","lineage":["https://openalex.org/I161103922"]},{"id":"https://openalex.org/I884002606","display_name":"Paul Ehrlich Institut","ror":"https://ror.org/00yssnc44","country_code":"DE","type":"facility","lineage":["https://openalex.org/I884002606"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Isabelle Bekeredjian-Ding","raw_affiliation_strings":["Division of Microbiology, Paul-Ehrlich-Institut","Institute for Medical Microbiology and Hospital Hygiene, Philipps-University of Marburg"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Microbiology, Paul-Ehrlich-Institut","institution_ids":["https://openalex.org/I884002606"]},{"raw_affiliation_string":"Institute for Medical Microbiology and Hospital Hygiene, Philipps-University of Marburg","institution_ids":["https://openalex.org/I161103922"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5072285340","display_name":"Benjamin Hofner","orcid":"https://orcid.org/0000-0003-2810-3186","observed_orcids":["https://orcid.org/0000-0003-2810-3186"]},"institutions":[{"id":"https://openalex.org/I181369854","display_name":"Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","ror":"https://ror.org/00f7hpc57","country_code":"DE","type":"education","lineage":["https://openalex.org/I181369854"]},{"id":"https://openalex.org/I884002606","display_name":"Paul Ehrlich Institut","ror":"https://ror.org/00yssnc44","country_code":"DE","type":"facility","lineage":["https://openalex.org/I884002606"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Benjamin Hofner","raw_affiliation_strings":["Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","Section Data Science and Methods, Paul-Ehrlich-Institut"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","institution_ids":["https://openalex.org/I181369854"]},{"raw_affiliation_string":"Section Data Science and Methods, Paul-Ehrlich-Institut","institution_ids":["https://openalex.org/I884002606"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5045608423"],"corresponding_institution_ids":["https://openalex.org/I884002606"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.75911372,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"13","issue":null,"first_page":"1931144","last_page":"1931144"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11943","display_name":"Pharmacovigilance and Adverse Drug Reactions","score":0.1639000028371811,"subfield":{"id":"https://openalex.org/subfields/3005","display_name":"Toxicology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11943","display_name":"Pharmacovigilance and Adverse Drug Reactions","score":0.1639000028371811,"subfield":{"id":"https://openalex.org/subfields/3005","display_name":"Toxicology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.1582999974489212,"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/T10873","display_name":"Bacterial Infections and Vaccines","score":0.11020000278949738,"subfield":{"id":"https://openalex.org/subfields/2404","display_name":"Microbiology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/vaccine-development","display_name":"vaccine development","score":0.6589999794960022},{"id":"https://openalex.org/keywords/monoclonal-antibodies","display_name":"monoclonal antibodies","score":0.9800000190734863},{"id":"https://openalex.org/keywords/regulatory-recommendations","display_name":"regulatory recommendations","score":0.578000009059906},{"id":"https://openalex.org/keywords/primary-endpoint","display_name":"primary endpoint","score":0.718999981880188},{"id":"https://openalex.org/keywords/statistical-analysis-plan","display_name":"statistical analysis plan","score":0.7609999775886536},{"id":"https://openalex.org/keywords/study-population-selection","display_name":"population selection","score":0.6019999980926514},{"id":"https://openalex.org/keywords/antibiotic-resistance","display_name":"antibiotic resistance","score":0.5199999809265137},{"id":"https://openalex.org/keywords/immune-evasion","display_name":"immune evasion","score":0.6769999861717224}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7391999959945679},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.5407999753952026},{"id":"https://openalex.org/C138816342","wikidata":"https://www.wikidata.org/wiki/Q189603","display_name":"Public health","level":2,"score":0.45210000872612},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.4390000104904175},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.4000999927520752},{"id":"https://openalex.org/C22070199","wikidata":"https://www.wikidata.org/wiki/Q192995","display_name":"Vaccination","level":2,"score":0.3912999927997589},{"id":"https://openalex.org/C177713679","wikidata":"https://www.wikidata.org/wiki/Q679690","display_name":"Intensive care medicine","level":1,"score":0.39089998602867126},{"id":"https://openalex.org/C512399662","wikidata":"https://www.wikidata.org/wiki/Q3505712","display_name":"Family medicine","level":1,"score":0.38580000400543213},{"id":"https://openalex.org/C2780441014","wikidata":"https://www.wikidata.org/wiki/Q7907952","display_name":"Vaccine efficacy","level":3,"score":0.36970001459121704},{"id":"https://openalex.org/C2779473830","wikidata":"https://www.wikidata.org/wiki/Q1540899","display_name":"MEDLINE","level":2,"score":0.3682999908924103},{"id":"https://openalex.org/C94665300","wikidata":"https://www.wikidata.org/wiki/Q63391344","display_name":"Antibiotic resistance","level":3,"score":0.35010001063346863},{"id":"https://openalex.org/C2780801004","wikidata":"https://www.wikidata.org/wiki/Q1415366","display_name":"Immunization","level":3,"score":0.3192000091075897},{"id":"https://openalex.org/C3018913218","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody response","level":3,"score":0.3158999979496002},{"id":"https://openalex.org/C204787440","wikidata":"https://www.wikidata.org/wiki/Q188504","display_name":"Alternative medicine","level":2,"score":0.3019999861717224},{"id":"https://openalex.org/C2780182762","wikidata":"https://www.wikidata.org/wiki/Q1630279","display_name":"Guideline","level":2,"score":0.3003000020980835},{"id":"https://openalex.org/C2779974597","wikidata":"https://www.wikidata.org/wiki/Q28448986","display_name":"Clinical Practice","level":2,"score":0.28790000081062317},{"id":"https://openalex.org/C2992053201","wikidata":"https://www.wikidata.org/wiki/Q2585693","display_name":"Clinical efficacy","level":2,"score":0.28360000252723694},{"id":"https://openalex.org/C203092338","wikidata":"https://www.wikidata.org/wiki/Q1340863","display_name":"Clinical endpoint","level":3,"score":0.2809999883174896},{"id":"https://openalex.org/C128544194","wikidata":"https://www.wikidata.org/wiki/Q474859","display_name":"Translational research","level":2,"score":0.26989999413490295},{"id":"https://openalex.org/C2992965680","wikidata":"https://www.wikidata.org/wiki/Q598976","display_name":"Clinical microbiology","level":2,"score":0.2621000111103058},{"id":"https://openalex.org/C2992293740","wikidata":"https://www.wikidata.org/wiki/Q4781752","display_name":"Drug approval","level":3,"score":0.2619999945163727}],"mesh":[],"locations_count":5,"locations":[{"id":"doi:10.3389/fmed.2026.1931144","doi":"https://doi.org/10.3389/fmed.2026.1931144","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fmed.2026.1931144","pdf_url":"https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1931144/pdf","source":{"id":"https://openalex.org/S2597052008","display_name":"Frontiers in Medicine","issn_l":"2296-858X","issn":["2296-858X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-70","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Medicine","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13692650","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13692650/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13692650/pdf/fmed-13-1931144.pdf","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":"Front Med (Lausanne)","raw_type":"Text"},{"id":"pmid:42921014","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42921014","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":"Frontiers in medicine","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:1f514dbf356643d49e21a47c02aed3c8","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/1f514dbf356643d49e21a47c02aed3c8","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Medicine, Vol 13 (2026)","raw_type":"article"},{"id":"pmh:oai:open.fau.de:openfau/42058","doi":null,"is_oa":true,"landing_page_url":"https://open.fau.de/handle/openfau/42058","pdf_url":null,"source":{"id":"https://openalex.org/S4306402340","display_name":"OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universit\u00e4tsbibliothek Erlangen-N\u00fcrnberg)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fmed.2026.1931144","doi":"https://doi.org/10.3389/fmed.2026.1931144","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fmed.2026.1931144","pdf_url":"https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1931144/pdf","source":{"id":"https://openalex.org/S2597052008","display_name":"Frontiers in Medicine","issn_l":"2296-858X","issn":["2296-858X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","norway-1","poland-70","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Medicine","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1462413426","display_name":"Collaboration for Prevention and Treatment of MDR Bacterial Infections","funder_award_id":"853967","funder_id":"https://openalex.org/F4320320300","funder_display_name":"European Commission"}],"funders":[{"id":"https://openalex.org/F4320314178","display_name":"European Federation of Pharmaceutical Industries and Associations","ror":"https://ror.org/00g1x4v36"},{"id":"https://openalex.org/F4320320300","display_name":"European Commission","ror":"https://ror.org/00k4n6c32"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7221102297.pdf","grobid_xml":"https://content.openalex.org/works/W7221102297.grobid-xml"},"referenced_works_count":25,"referenced_works":["https://openalex.org/W2026726206","https://openalex.org/W2037869200","https://openalex.org/W2135922137","https://openalex.org/W2582069104","https://openalex.org/W2791781902","https://openalex.org/W3011719258","https://openalex.org/W3014273779","https://openalex.org/W3047142763","https://openalex.org/W3110118663","https://openalex.org/W4206677002","https://openalex.org/W4210396642","https://openalex.org/W4311471854","https://openalex.org/W4382585357","https://openalex.org/W4383273076","https://openalex.org/W4389430461","https://openalex.org/W4392203976","https://openalex.org/W4396583556","https://openalex.org/W4397003314","https://openalex.org/W4399622003","https://openalex.org/W4402557213","https://openalex.org/W4404470077","https://openalex.org/W4405887858","https://openalex.org/W4406573561","https://openalex.org/W4412396277","https://openalex.org/W7152692553"],"related_works":["https://openalex.org/W7106133365","https://openalex.org/W7093335998","https://openalex.org/W7092287868","https://openalex.org/W2740512057","https://openalex.org/W4401412386","https://openalex.org/W6920849773","https://openalex.org/W2526886499","https://openalex.org/W6939792139","https://openalex.org/W2938056705","https://openalex.org/W3184437083"],"abstract_inverted_index":{"Background:":[0],")":[1],"remains":[2],"a":[3,152,304],"major":[4],"public":[5],"health":[6],"concern":[7],"due":[8,269],"to":[9,143,150,157,174,203,208,251,256,270,320],"their":[10],"treatment":[11],"resistance":[12],"and":[13,17,30,66,74,86,89,122,149,177,195,199,273,284,300,314,323],"immune":[14],"evasion.":[15],"Vaccines":[16],"monoclonal":[18],"antibodies":[19],"(mAbs)":[20],"are":[21,318],"promising":[22],"solutions,":[23],"yet":[24],"only":[25],"one":[26],"mAb":[27,179],"is":[28,289],"licensed":[29],"no":[31,307],"vaccine":[32,176],"has":[33],"reached":[34],"that":[35,82],"stage.":[36],"To":[37,181],"identify":[38,252],"recurring":[39],"clinical":[40,91,140,198,327],"challenges,":[41],"we":[42,109],"analyzed":[43],"final":[44],"advice":[45],"letters":[46],"(FALs)":[47],"issued":[48],"through":[49],"the":[50,62,67,84,106,158,169,186,209,248,264],"European":[51],"Medicines":[52],"Agency's":[53],"(EMA)":[54],"Scientific":[55],"Advice":[56],"procedure.":[57],"Methods:":[58],"We":[59,79,93,136,162],"searched":[60],"both":[61],"Paul-Ehrlich-Institut":[63],"local":[64],"database":[65,69],"EMA":[68],"for":[70,166,242],"FALs":[71,81,165],"on":[72,98,215,246,261],"vaccines":[73,283],"mAbs":[75,285],"targeting":[76],"ESCAPE":[77,287],"pathogens.":[78],"included":[80,107,163],"matched":[83],"pathogen":[85,292],"product":[87],"criteria":[88,250],"addressed":[90],"development.":[92],"excluded":[94],"those":[95,253],"focused":[96,245],"solely":[97],"quality,":[99],"non-clinical,":[100],"safety,":[101],"or":[102,133,225,230,238],"post-marketing":[103],"aspects.":[104],"From":[105],"FALs,":[108],"extracted":[110],"information":[111],"across":[112,185],"four":[113],"main":[114],"categories:":[115],"primary":[116,187],"endpoint,":[117],"statistical":[118,265],"analyses,":[119],"study":[120,123,243],"population,":[121],"design.":[124],"Regulatory":[125],"responses":[126],"were":[127,147],"classified":[128],"as":[129,220],"fully,":[130],"silently,":[131],"partially,":[132],"not":[134],"endorsed.":[135],"subsequently":[137],"reviewed":[138],"related":[139,173],"trial":[141,298],"protocols":[142],"assess":[144],"whether":[145],"recommendations":[146],"implemented":[148],"provide":[151],"narrative":[153],"summary":[154],"of":[155,168,206,223,282],"changes":[156,262],"development":[159,281,309,328],"programs.":[160,329],"Results:":[161],"14":[164],"each":[167],"two":[170],"medicine":[171],"categories,":[172],"six":[175],"13":[178],"trials.":[180,278],"address":[182],"common":[183],"challenges":[184],"endpoints,":[188],"regulators":[189],"recommended":[190],"selecting":[191],"single,":[192],"infection-related":[193],"endpoints":[194],"emphasized":[196],"precise":[197],"laboratory":[200],"case":[201],"definitions":[202],"ensure":[204],"attribution":[205],"infection":[207,295],"target":[210],"pathogen.":[211],"They":[212],"further":[213],"advised":[214,260],"incorporating":[216],"supportive":[217],"evidence,":[218],"such":[219],"subgroup":[221],"analyses":[222],"cases":[224],"inflammation":[226],"markers,":[227],"direct":[228],"microbiological":[229],"indirect":[231],"measures":[232],"(e.g.,":[233],"antibiotic":[234],"use,":[235],"hospital":[236],"stay),":[237],"survival-related":[239],"endpoints.":[240],"Recommendations":[241],"populations":[244],"refining":[247],"inclusion/exclusion":[249],"most":[254],"likely":[255],"benefit.":[257],"Regulators":[258],"also":[259],"in":[263],"analysis":[266],"plan":[267],"(mainly":[268],"lower-than-expected":[271],"incidence)":[272],"generally":[274],"discouraged":[275],"single":[276],"pivotal":[277],"Conclusion:":[279],"The":[280],"against":[286],"pathogens":[288],"challenged":[290],"by":[291],"diversity,":[293],"unpredictable":[294],"rates,":[296],"heterogeneous":[297],"populations,":[299],"diagnostic":[301],"uncertainty.":[302],"In":[303],"field":[305],"with":[306],"one-size-fits-all":[308],"pathway,":[310],"early":[311],"regulatory":[312],"interaction":[313],"multidisciplinary":[315],"disease-expert":[316],"input":[317],"essential":[319],"reduce":[321],"uncertainty":[322],"support":[324],"robust,":[325],"efficient":[326]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-10-10T00:00:00"}