title: Suspected survivor bias in case-control studies: stratify on survival time and use a negative control.
abstract: OBJECTIVE
  Selection bias in case-control studies occurs when control selection is inappropriate. However, selection bias due to improper case sampling is less well recognized. We describe how to recognize survivor bias (i.e., selection on exposed cases) and illustrate this with an example study.
  
  
  METHODS
  A case-control study was used to analyze the effect of statins on major bleedings during treatment with vitamin K antagonists. A total of 110 patients who experienced such bleedings were included 18-1,018 days after the bleeding complication and matched to 220 controls.
  
  
  RESULTS
  A protective association of major bleeding for exposure to statins (odds ratio [OR]: 0.56; 95% confidence interval: 0.29-1.08) was found, which did not become stronger after adjustment for confounding factors. These observations lead us to suspect survivor bias. To identify this bias, results were stratified on time between bleeding event and inclusion, and repeated for a negative control (an exposure not related to survival): blood group non-O. The ORs for exposure to statins increased gradually to 1.37 with shorter time between outcome and inclusion, whereas ORs for the negative control remained constant, confirming our hypothesis.
  
  
  CONCLUSIONS
  We recommend the presented method to check for overoptimistic results, that is, survivor bias in case-control studies.
authors: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: n.van_rein@lumc.nl.
authors: Nienke
authors: N
authors: van Rein
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Suzanne C
authors: SC
authors: Cannegieter
authors: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Frits R
authors: FR
authors: Rosendaal
authors: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors: Pieter H
authors: PH
authors: Reitsma
authors: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Willem M
authors: WM
authors: Lijfering
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects; D016022:Case-Control Studies; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D016017:Odds Ratio; D015983:Selection Bias; D017741:Survivors; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014812:Vitamin K
keywords: Anticoagulants; Case–control studies; Epidemiology; Hemorrhage; Hydroxymethylglutaryl-CoA reductase inhibitors; Selection bias