title: Benefit-harm analysis and charts for individualized and preference-sensitive prevention: example of low dose aspirin for primary prevention of cardiovascular disease and cancer.
abstract: BACKGROUND
  Clinical practice guidelines provide separate recommendations for different diseases that may be prevented or treated by the same intervention. Also, they commonly provide recommendations for entire populations but not for individuals. To address these two limitations, our aim was to conduct benefit-harm analyses for a wide range of individuals using the example of low dose aspirin for primary prevention of cardiovascular disease and cancer and to develop Benefit-Harm Charts that show the overall benefit-harm balance for individuals.
  
  
  METHODS
  We used quantitative benefit-harm modeling that included 16 outcomes to estimate the probability that low dose aspirin provides more benefits than harms for a wide range of men and women between 45 and 84 years of age and without a previous myocardial infarction, severe ischemic stroke, or cancer. We repeated the quantitative benefit-harm modeling for different combinations of age, sex, and outcome risks for severe ischemic and hemorrhagic stroke, myocardial infarction, cancers, and severe gastrointestinal bleeds. The analyses considered weights for the outcomes, statistical uncertainty of the effects of aspirin, and death as a competing risk. We constructed Benefit-Harm Charts that show the benefit-harm balance for different combinations of outcome risks.
  
  
  RESULTS
  The Benefit-Harm Charts ( http://www.benefit-harm-balance.com ) we have created show that the benefit-harm balance differs largely across a primary prevention population. Low dose aspirin is likely to provide more benefits than harms in men, elderly people, and in those at low risk for severe gastrointestinal bleeds. Individual preferences have a major impact on the benefit-harm balance. If, for example, it is a high priority for individuals to prevent stroke and severe cancers while severe gastrointestinal bleeds are deemed to be of little importance, the benefit-harm balance is likely to favor low dose aspirin for most individuals. Instead, if severe gastrointestinal bleeds are judged to be similarly important compared to the benefit outcomes, low dose aspirin is unlikely to provide more benefits than harms.
  
  
  CONCLUSIONS
  Benefit-Harm Charts support individualized benefit-harm assessments and decision making. Similarly, individualized benefit-harm assessments may allow guideline developers to issue more finely granulated recommendations that reduce the risk of over- and underuse of interventions. The example of low dose aspirin for primary prevention of cardiovascular disease and cancer shows that it may be time for guideline developers to provide combined recommendations for different diseases that may be prevented or treated by the same intervention.
authors.affiliation: Department of Epidemiology; Epidemiology, Biostatistics & Prevention Institute, University of Zurich, Hirschengraben 84, Room HRS G29, CH-8001, Zurich, Switzerland. miloalan.puhan@uzh.ch.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. miloalan.puhan@uzh.ch.
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.affiliation: Department of Epidemiology; Epidemiology, Biostatistics & Prevention Institute, University of Zurich, Hirschengraben 84, Room HRS G29, CH-8001, Zurich, Switzerland. tsung.yu@uzh.ch.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. tsung.yu@uzh.ch.
authors.forename: Tsung
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. I.Stegeman@umcutrecht.nl.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. I.Stegeman@umcutrecht.nl.
authors.forename: Inge
authors.initials: I
authors.lastname: Stegeman
authors.affiliation: Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA. ravi.varadhan@jhu.edu.|Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, USA. ravi.varadhan@jhu.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.affiliation: Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, USA. ssingh31@jhu.edu.
authors.forename: Sonal
authors.initials: S
authors.lastname: Singh
authors.affiliation: Center on Aging and Health, Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, USA. cyboyd@jhmi.edu.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Boyd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000517:prevention & control*; D011322:Primary Prevention / Q000379:methods*; D018570:Risk Assessment / Q000379:methods*
chemical_list: D001241:Aspirin