title: Classification of treatment-related mortality in children with cancer: a systematic assessment.
abstract: Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause-of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (κ=0·83, 95% CI 0·60-1·00) and paediatric oncologists (0·84, 0·63-1·00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0·92, 0·78-1·00). Our approach should allow comparison of treatment-related mortality across trials and across time.
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Alexander
authors.affiliation: Pediatric Oncology Group of Ontario, Toronto, ON, Canada.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Pole
authors.affiliation: Division of Haematology/Oncology, Children's Hospital, London Health Sciences Centre, London, ON, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Gibson
authors.affiliation: Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.affiliation: Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Hesser
authors.affiliation: Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Chi
authors.affiliation: Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco Medical Center-Mission Bay, San Francisco, CA, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Fisher
authors.affiliation: Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Kanerva
authors.affiliation: Department of Paediatrics, University Medical Centre Schleswig-Holstein, Kiel, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.affiliation: Centre for Reviews and Dissemination, University of York, York, UK.
authors.forename: Bob
authors.initials: B
authors.lastname: Phillips
authors.affiliation: Division of Pediatric Hematology/Oncology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Raetz
authors.affiliation: Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.affiliation: Department of Paediatric Haematology, Great Ormond Street Hospital, London, UK.
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
authors.affiliation: Department of Paediatric Oncology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Tissing
authors.affiliation: Department of Paediatric Haematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: lillian.sung@sickkids.ca.
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000145:classification; D002423:Cause of Death; D002648:Child; D046688:Child Mortality; D002675:Child, Preschool; D032921:Consensus; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000175:diagnosis / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000145:classification / Q000401:mortality*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D009369:Neoplasms / Q000401:mortality* / Q000628:therapy*; D018570:Risk Assessment; D012307:Risk Factors; D009626:Terminology as Topic; D013997:Time Factors; D016896:Treatment Outcome