title: Crohn's disease patients' risk-benefit preferences: serious adverse event risks versus treatment efficacy.
abstract: OBJECTIVE
  Regulatory assessments of drug risks do not routinely consider patient preferences, despite evidence that some patients are willing to accept increased side-effect risk in exchange for therapeutic benefits. The aim of this study is to estimate the willingness of Crohn's disease (CD) patients to accept life-threatening adverse event risks in exchange for CD symptom relief.
  
  
  METHODS
  Patients with CD completed choice-format conjoint trade-off tasks involving hypothetical treatments with varying efficacy and risk levels. The treatment features included daily symptoms and activity limitations, serious complications (fistulas, abscesses, bowel obstructions), time between flare-ups, oral steroid use and risk of 3 serious adverse events (SAEs) known to be associated with CD treatment (progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma). The mean maximum acceptable annual risk (MAR) for each of the SAEs was calculated for various levels of clinical benefit.
  
  
  RESULTS
  Daily symptom severity was the most important factor in treatment preferences. Higher MAR was observed for trade-off tasks involving higher levels of clinical benefit. The MAR was similar across the 3 SAEs. For improvements from severe daily symptoms to remission and from moderate daily symptoms to remission, the MARs ranged from 0.69% to 0.81% and from 0.39% to 0.55%, respectively.
  
  
  CONCLUSIONS
  Patients with CD have well-defined preferences among treatment attributes and are willing to accept tradeoffs among attributes. The patients indicated they are willing to accept elevated SAE risks in exchange for clinical efficacy. The perspective of the patients on the benefit versus risk balance can assist in making treatment and regulatory decisions.
authors.affiliation: Research Triangle Institute/RTI International, Research Triangle Park, North Carolina, USA. frjohnson@rti.org
authors.forename: F Reed
authors.initials: FR
authors.lastname: Johnson
authors.forename: Semra
authors.initials: S
authors.lastname: Ozdemir
authors.forename: Carol
authors.initials: C
authors.lastname: Mansfield
authors.forename: Steven
authors.initials: S
authors.lastname: Hass
authors.forename: David W
authors.initials: DW
authors.lastname: Miller
authors.forename: Corey A
authors.initials: CA
authors.lastname: Siegel
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006306:Health Surveys; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab; D017060:Patient Satisfaction; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013256:Steroids / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D013256:Steroids