title: Quality-of-life-adjusted hazard of death: a formulation of the quality-adjusted life-years model of use in benefit-risk assessment.
abstract: BACKGROUND
  Although the quality-adjusted life-years (QALY) model is standard in health technology assessment, quantitative methods are less frequent but increasingly used for benefit-risk assessment (BRA) at earlier stages of drug development. A frequent challenge when implementing metrics for BRA is to weigh the importance of effects on a chronic condition against the risk of severe events during the trial. The lifetime component of the QALY model has a counterpart in the BRA context, namely, the risk of dying during the study.
  
  
  METHODS
  A new concept is presented, the hazard of death function that a subject is willing to accept instead of the baseline hazard to improve his or her chronic health status, which we have called the quality-of-life-adjusted hazard of death.
  
  
  RESULTS
  It has been proven that if assumptions of the linear QALY model hold, the excess mortality rate tolerated by a subject for a chronic health improvement is inversely proportional to the mean residual life.
  
  
  CONCLUSIONS
  This result leads to a new representation of the linear QALY model in terms of hazard rate functions and allows utilities obtained by using standard methods involving trade-offs of life duration to be translated into thresholds of tolerated mortality risk during a short period of time, thereby avoiding direct trade-offs using small probabilities of events during the study, which is known to lead to bias and variability.
authors.affiliation: Astellas Pharma Global Development Europe, Sylviusweg 62, Leiden, The Netherlands. Electronic address: alberto.garciahernandez@astellas.com.
authors.forename: Alberto
authors.initials: A
authors.lastname: Garcia-Hernandez
mesh_terms: D015982:Bias; D003362:Cost-Benefit Analysis; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000401:mortality*; D006801:Humans; D016014:Linear Models; D015233:Models, Statistical; D011336:Probability; D016016:Proportional Hazards Models; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment / Q000379:methods; D013997:Time Factors
keywords: benefit-risk assessment; hazard function; mean residual life; quality-adjusted life-years; tolerated risk