{"id":"https://openalex.org/W7203961078","doi":null,"title":"Optimizing Relapse Prevention and Treatment Strategies in Childhood Nephrotic Syndrome using Target Trial Emulation and Adaptive Clinical Trial Methods","display_name":"Optimizing Relapse Prevention and Treatment Strategies in Childhood Nephrotic Syndrome using Target Trial Emulation and Adaptive Clinical Trial Methods","publication_year":2026,"publication_date":"2026-06-01","ids":{"openalex":"https://openalex.org/W7203961078"},"language":"en","primary_location":{"id":"pmh:oai:utoronto.scholaris.ca:1807/153738","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/1807/153738","pdf_url":"https://utoronto.scholaris.ca/bitstreams/335adf8f-3585-4c6a-a109-dcdb79c658a0/download","source":{"id":"https://openalex.org/S4306400261","display_name":"TSpace (University of Toronto)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I185261750","host_organization_name":"University of Toronto","host_organization_lineage":["https://openalex.org/I185261750"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"volume":null,"type":"dissertation","indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://utoronto.scholaris.ca/bitstreams/335adf8f-3585-4c6a-a109-dcdb79c658a0/download","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5022797938","display_name":"Cal Robinson","orcid":"https://orcid.org/0000-0002-2223-0646","observed_orcids":["https://orcid.org/0000-0002-2223-0646"]},"institutions":[{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]}],"countries":["CA"],"is_corresponding":true,"raw_author_name":"Robinson, Cal","raw_affiliation_strings":["Clinical Epidemiology and Health Care Research Institute of Health Policy, Management , and Evaluation University of Toronto","Doctor of Philosophy , Clinical Epidemiology and Health Care Research Institute of Health Policy, Management , and Evaluation University of Toronto 2026"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Epidemiology and Health Care Research Institute of Health Policy, Management , and Evaluation University of Toronto","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"Doctor of Philosophy , Clinical Epidemiology and Health Care Research Institute of Health Policy, Management , and Evaluation University of Toronto 2026","institution_ids":["https://openalex.org/I185261750"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5022797938"],"corresponding_institution_ids":["https://openalex.org/I185261750"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.5595999956130981,"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"}},"topics":[{"id":"https://openalex.org/T11235","display_name":"Statistical Methods in Clinical Trials","score":0.5595999956130981,"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/T11029","display_name":"Renal Diseases and Glomerulopathies","score":0.42289999127388,"subfield":{"id":"https://openalex.org/subfields/2727","display_name":"Nephrology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10408","display_name":"Chronic Kidney Disease and Diabetes","score":0.0015999999595806003,"subfield":{"id":"https://openalex.org/subfields/2727","display_name":"Nephrology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pediatric-nephrotic-syndrome","display_name":"pediatric nephrotic syndrome","score":0.8799999952316284},{"id":"https://openalex.org/keywords/relapse-prevention","display_name":"relapse prevention","score":0.968999981880188},{"id":"https://openalex.org/keywords/cyclophosphamide","display_name":"cyclophosphamide","score":0.925000011920929},{"id":"https://openalex.org/keywords/calcineurin-inhibitors","display_name":"calcineurin inhibitors","score":0.9980000257492065},{"id":"https://openalex.org/keywords/low-dose-corticosteroid-therapy","display_name":"low-dose corticosteroid therapy","score":0.7300000190734863},{"id":"https://openalex.org/keywords/steroid-sparing-immunosuppression","display_name":"steroid-sparing immunosuppression","score":0.8849999904632568},{"id":"https://openalex.org/keywords/target-trial-emulation","display_name":"target trial emulation","score":0.9480000138282776},{"id":"https://openalex.org/keywords/feasibility","display_name":"feasibility","score":0.3050000071525574},{"id":"https://openalex.org/keywords/pediatric-nephrology","display_name":"pediatric nephrology","score":0.6539999842643738},{"id":"https://openalex.org/keywords/internal-pilot-study","display_name":"internal pilot study","score":0.6589999794960022},{"id":"https://openalex.org/keywords/operating-characteristics","display_name":"operating characteristics","score":0.46799999475479126},{"id":"https://openalex.org/keywords/sample-size-reduction","display_name":"sample size reduction","score":0.5550000071525574},{"id":"https://openalex.org/keywords/type-i-error","display_name":"type I error","score":0.6959999799728394}],"concepts":[{"id":"https://openalex.org/C128057223","wikidata":"https://www.wikidata.org/wiki/Q420566","display_name":"Calcineurin","level":3,"score":0.7595999836921692},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.738099992275238},{"id":"https://openalex.org/C2778930706","wikidata":"https://www.wikidata.org/wiki/Q504790","display_name":"Nephrotic syndrome","level":2,"score":0.7249000072479248},{"id":"https://openalex.org/C168563851","wikidata":"https://www.wikidata.org/wiki/Q1436668","display_name":"Randomized controlled trial","level":2,"score":0.609499990940094},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.5837000012397766},{"id":"https://openalex.org/C129848803","wikidata":"https://www.wikidata.org/wiki/Q2564360","display_name":"Sample size determination","level":2,"score":0.45329999923706055},{"id":"https://openalex.org/C2776755627","wikidata":"https://www.wikidata.org/wiki/Q408524","display_name":"Cyclophosphamide","level":3,"score":0.43689998984336853},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.335099995136261},{"id":"https://openalex.org/C2780252810","wikidata":"https://www.wikidata.org/wiki/Q1455316","display_name":"Immunosuppression","level":2,"score":0.3278999924659729},{"id":"https://openalex.org/C149810388","wikidata":"https://www.wikidata.org/wiki/Q5374873","display_name":"Emulation","level":2,"score":0.3061999976634979},{"id":"https://openalex.org/C107673813","wikidata":"https://www.wikidata.org/wiki/Q812534","display_name":"Bayesian probability","level":2,"score":0.29899999499320984},{"id":"https://openalex.org/C2778653478","wikidata":"https://www.wikidata.org/wiki/Q1054718","display_name":"Kidney disease","level":2,"score":0.2946999967098236},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.2815999984741211},{"id":"https://openalex.org/C2779318504","wikidata":"https://www.wikidata.org/wiki/Q1438035","display_name":"Research design","level":2,"score":0.25999999046325684},{"id":"https://openalex.org/C2781413609","wikidata":"https://www.wikidata.org/wiki/Q7308373","display_name":"Regimen","level":2,"score":0.25540000200271606},{"id":"https://openalex.org/C2780303639","wikidata":"https://www.wikidata.org/wiki/Q740909","display_name":"Kidney transplantation","level":3,"score":0.25049999356269836}],"mesh":[],"locations_count":1,"locations":[{"id":"pmh:oai:utoronto.scholaris.ca:1807/153738","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/1807/153738","pdf_url":"https://utoronto.scholaris.ca/bitstreams/335adf8f-3585-4c6a-a109-dcdb79c658a0/download","source":{"id":"https://openalex.org/S4306400261","display_name":"TSpace (University of Toronto)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I185261750","host_organization_name":"University of Toronto","host_organization_lineage":["https://openalex.org/I185261750"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"}],"best_oa_location":{"id":"pmh:oai:utoronto.scholaris.ca:1807/153738","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/1807/153738","pdf_url":"https://utoronto.scholaris.ca/bitstreams/335adf8f-3585-4c6a-a109-dcdb79c658a0/download","source":{"id":"https://openalex.org/S4306400261","display_name":"TSpace (University of Toronto)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I185261750","host_organization_name":"University of Toronto","host_organization_lineage":["https://openalex.org/I185261750"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.7940486669540405}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320322015","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087"},{"id":"https://openalex.org/F4320334506","display_name":"Canadian Institutes of Health Research","ror":"https://ror.org/01gavpb45"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7203961078.pdf","grobid_xml":"https://content.openalex.org/works/W7203961078.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4409472426","https://openalex.org/W4414785246","https://openalex.org/W4406866288","https://openalex.org/W4403812398","https://openalex.org/W2157760822","https://openalex.org/W4238506241","https://openalex.org/W1819085895","https://openalex.org/W7100815280","https://openalex.org/W4206567694","https://openalex.org/W2122941588"],"abstract_inverted_index":{"Background:Nephrotic":[0],"syndrome":[1,51,157,270],"is":[2,299,334],"one":[3],"of":[4,34,43,58,78,107,143,196],"the":[5,41,55,141,216,234],"most":[6],"common":[7],"childhood":[8,326,344],"kidney":[9,186],"diseases.":[10],"Frequent":[11],"relapses":[12,25],"and":[13,26,45,74,131,198,220,244,284,302,311],"high":[14],"cumulative":[15],"steroid":[16,28,153,340],"exposure":[17],"cause":[18],"substantial":[19],"harm.":[20],"Effective":[21],"strategies":[22,342],"to":[23,38,122,139,209,232,304,319,336],"prevent":[24],"reduce":[27],"burden":[29],"are":[30],"needed.":[31],"The":[32,247],"objectives":[33],"this":[35,79],"thesis":[36],"were":[37,272,282],"1)":[39],"compare":[40],"effectiveness":[42,322],"cyclophosphamide":[44,92,173],"calcineurin":[46,94,170],"inhibitors":[47],"for":[48,71,155,256,339],"preventing":[49],"nephrotic":[50,101,156,269,330,345],"relapses,":[52,181],"2)":[53],"determine":[54],"optimal":[56,235],"design":[57,236],"a":[59,82,108,144,257,263,275,294,306],"Bayesian":[60,110,146,296,312],"adaptive":[61,111,147,212,297,313],"randomized":[62],"controlled":[63],"trial":[64,89,116],"(RCT)":[65],"comparing":[66,91,149],"low-dose":[67,150,285],"vs.":[68,93,151,172],"standard-dose":[69,152],"steroids":[70,286],"relapse":[72,271],"treatment,":[73],"3)":[75],"establish":[76],"feasibility":[77,142,280],"RCT":[80,148,213,298,314],"through":[81],"pilot":[83,137,276],"study.":[84],"Methods:":[85],"Aim":[86,103,134,202,260],"1:":[87,160],"Target":[88],"emulation":[90],"inhibitor":[95,171,189],"treatment":[96,154,190],"in":[97,174,274,324,343],"children":[98,267],"with":[99,193,215,268],"steroid-sensitive":[100],"syndrome.":[102,331,346],"2:":[104,203],"Simulation":[105],"study":[106,138],"planned":[109,145],"RCT.":[112,277],"For":[113],"each":[114],"candidate":[115],"design,":[117],"we":[118],"simulated":[119,205,227],"10,000":[120],"trials":[121,208,231],"estimate":[123],"operating":[124],"characteristics":[125],"(power,":[126],"type":[127,221],"1":[128,222],"error":[129,223],"rate,":[130,243],"sample":[132,218,249],"size).":[133],"3:":[135,261],"Internal":[136],"evaluate":[140],"relapses.":[158],"Results:Aim":[159],"During":[161],"median":[162],"5.5-year":[163],"follow-up,":[164],"there":[165],"was":[166,191,252],"no":[167],"difference":[168],"between":[169],"time-to-relapse":[175],"(HR":[176],"1.25,":[177],"95%CI":[178],"0.84-1.87),":[179],"subsequent":[180],"steroid-sparing":[182],"immunosuppression":[183],"use,":[184],"or":[185],"function.":[187],"Calcineurin":[188],"associated":[192],"higher":[194],"risks":[195],"hospitalization":[197],"intravenous":[199],"albumin":[200],"use.":[201],"We":[204,226],"5.4":[206],"million":[207,230],"identify":[210,233],"three":[211],"designs":[214],"lowest":[217],"size":[219,250],"rate":[224],"<5%.":[225],"another":[228],"1.2":[229],"under":[237],"varying":[238],"conditions":[239],"(treatment":[240],"effect,":[241],"recruitment":[242],"prior":[245],"distributions).":[246],"estimated":[248],"required":[251],"71%":[253],"lower":[254],"than":[255],"fixed-sample":[258],"design.":[259],"Over":[262],"10-month":[264],"period,":[265],"40":[266],"enrolled":[273],"All":[278],"pre-specified":[279],"targets":[281],"met,":[283],"had":[287],"acceptable":[288],"safety.":[289],"These":[290],"findings":[291],"suggest":[292],"that":[293],"full-scale":[295],"feasible,":[300],"safe,":[301],"likely":[303],"reach":[305],"conclusive":[307],"outcome.":[308],"Conclusions:Causal":[309],"inference":[310],"methods":[315],"can":[316],"be":[317],"used":[318],"answer":[320],"comparative":[321],"questions":[323],"rare":[325],"diseases,":[327],"such":[328],"as":[329],"Further":[332],"research":[333],"needed":[335],"advance":[337],"evidence":[338],"minimization":[341]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-08-22T00:00:00"}