title: Survival Bias When Assessing Risk Factors for Age-Related Macular Degeneration: A Tutorial with Application to the Exposure of Smoking.
abstract: We illustrate the effect of survival bias when investigating risk factors for eye disease in elderly populations for whom death is a competing risk. Our investigation focuses on the relationship between smoking and late age-related macular degeneration (AMD) in an observational study impacted by censoring due to death.
  
  
  
  Statistical methodology to calculate the survivor average causal effect (SACE) as a sensitivity analysis is described, including example statistical computing code for Stata and R. To demonstrate this method, we examine the causal effect of smoking history at baseline (1990-1994) on the presence of late AMD at the third study wave (2003-2007) using data from the Melbourne Collaborative Cohort Study.
  
  
  
  Of the 40,506 participants eligible for inclusion, 38,092 (94%) survived until the start of the third study wave, 20,752 (51%) were graded for AMD (60% female, aged 47-85 years, mean 65 ± 8.7 years). Late AMD was detected in 122 participants. Logistic regression showed strong evidence of an increased risk of late AMD for current smokers compared to non-smokers (adjusted naïve odds ratio 2.99, 95% confidence interval, CI, 1.74-5.13). Among participants expected to be alive at the start of follow-up regardless of their smoking status, the estimated SACE odds ratio comparing current smokers to non-smokers was at least 3.42 (95% CI 1.57-5.15).
  
  
  
  Survival bias can attenuate associations between harmful exposures and diseases of aging. Estimation of the SACE using a sensitivity analysis approach should be considered when conducting epidemiological research within elderly populations.
authors.affiliation: a Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital , Melbourne , Australia.|b Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health , University of Melbourne , Melbourne , Australia.|c Ophthalmology, Department of Surgery , University of Melbourne , Melbourne , Australia.
authors.forename: Myra B
authors.identifier: 0000-0002-5422-040X
authors.initials: MB
authors.lastname: McGuinness
authors.affiliation: b Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health , University of Melbourne , Melbourne , Australia.
authors.forename: Amalia
authors.initials: A
authors.lastname: Karahalios
authors.affiliation: d Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kasza
authors.affiliation: a Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital , Melbourne , Australia.|c Ophthalmology, Department of Surgery , University of Melbourne , Melbourne , Australia.
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.affiliation: a Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital , Melbourne , Australia.|c Ophthalmology, Department of Surgery , University of Melbourne , Melbourne , Australia.|e Department of Ophthalmology , University of Bonn , Bonn , Germany.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Finger
authors.affiliation: b Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health , University of Melbourne , Melbourne , Australia.|f Cancer Epidemiology Centre, Cancer Council Victoria , Melbourne , Australia.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Simpson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D014739:Victoria / Q000453:epidemiology
keywords: Age-related macular degeneration; causal methodology; death; smoking; survival bias