title: Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults.
abstract: OBJECTIVE
  Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention.
  
  
  OBJECTIVE
  To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease.
  
  
  METHODS
  Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease.
  
  
  METHODS
  Level of estimated glomerular filtration rate (eGFR) and proteinuria.
  
  
  METHODS
  Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25.
  
  
  RESULTS
  The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses.
  
  
  CONCLUSIONS
  Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.
authors.affiliation: Department of Medicine, Department of Veterans Affairs Puget Sound Healthcare System, Seattle, Washington2Department of Medicine, University of Washington, Seattle3Group Health Research Institute, Seattle, Washington.
authors.forename: Ann M
authors.initials: AM
authors.lastname: O'Hare
authors.affiliation: Veterans Engineering Resource Center, Department of Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennyslvania5Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: John R
authors.initials: JR
authors.lastname: Hotchkiss
authors.affiliation: Department of Medicine, Department of Veterans Affairs Palo Alto Healthcare System, Palo Alto, California7Department of Medicine, Stanford University Medical Center, Palo Alto, California.
authors.forename: Manjula
authors.initials: M
authors.lastname: Kurella Tamura
authors.affiliation: Department of Medicine, University of Washington, Seattle3Group Health Research Institute, Seattle, Washington.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.affiliation: Department of Medicine, Department of Veterans Affairs Puget Sound Healthcare System, Seattle, Washington.
authors.forename: Adam
authors.initials: A
authors.lastname: Batten
authors.affiliation: Department of Medicine, Department of Veterans Affairs Puget Sound Healthcare System, Seattle, Washington9currently with Amgen, Thousand Oaks, California.
authors.forename: Thy P
authors.initials: TP
authors.lastname: Do
authors.affiliation: Department of Medicine, Department of Veterans Affairs Medical Center, San Francisco, San Francisco, California11Department of Medicine, University of California, San Francisco.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Covinsky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors