title: Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement.
abstract: BACKGROUND
  Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis. An increasing number of treating physicians and patients are showing interest in patient-tailored approaches to prophylaxis, which aim to harmonize the prophylaxis regimen with the patients' bleeding phenotype, levels of physical activity and a variety of other variables.
  
  
  METHODS
  A modified Delphi technique was adopted to generate consensus. The expert panel met in person to set the objectives, be trained on the Delphi technique and agree on the desired level of consensus. Three iterations were used to identify the targets, the scenarios and their combinations.
  
  
  RESULTS
  Twenty-eight scenarios and eight target levels were identified and used to issue recommendations. The panel reached the desired level of consensus on positive or negative recommendations. Areas where consensus was not reached were identified and proposed as areas for future research. Prospective assessment of the validity of most of the proposed targets is recommended.
  
  
  CONCLUSIONS
  We have generated, by expert consensus, target plasma levels of factor concentrate to be used to tailor treatment for persons with haemophilia.
authors.affiliation: Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-3331-8766
authors.initials: A
authors.lastname: Iorio
authors.affiliation: Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Iserman
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Blanchette
authors.affiliation: Guy's and St Thomas' Hospital, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Dolan
authors.affiliation: Haemophilia Centre Rhine Main - HZRM, Moerfelden-Walldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Escuriola Ettingshausen
authors.affiliation: Haemostasis and Thrombosis Unit, Division of Haematology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Hermans
authors.affiliation: Division of Haematology, Louis Pradel Cardiology hospital, University Claude Bernard Lyon1, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Negrier
authors.affiliation: University Clinic Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Global Medical Affairs Hematology, Baxalta Innovations GmbH, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Reininger
authors.affiliation: Department of Orthopaedic Surgery, La Paz University Hospital, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Merchan
authors.affiliation: Department of Transfusion Medicine and Hemostasis, University Hospital Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Spannagl
authors.affiliation: Rush University and Baxalta, US, Inc., Deerfield, IL, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Valentino
authors.affiliation: Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.affiliation: Global Medical Affairs Hematology, Baxalta Innovations GmbH, Vienna, Austria.
authors.forename: K N
authors.initials: KN
authors.lastname: Steinitz-Trost
authors.affiliation: Global Medical Affairs Hematology, Baxalta Innovations GmbH, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Gringeri
mesh_terms: D032921:Consensus; D003697:Delphi Technique; D005164:Factor IX / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D006467:Hemophilia A / Q000097:blood* / Q000628:therapy*; D006801:Humans; D057285:Precision Medicine; D011795:Surveys and Questionnaires
chemical_list: D005169:Factor VIII; D005164:Factor IX
keywords: haemophilia; individualization; personalized; prophylaxis; tailoring