American Journal of Kidney Diseases
Volume 48, Issue 1 , Pages 159-166 , July 2006

Surrogate Markers in Clinical Studies: Problems Solved or Created?

  • Braden Manns, MD

      Affiliations

    • Departments of Medicine and Community Health Sciences, University of Calgary, Institute of Health Economics, Edmonton, Alberta, Canada
    • ,
  • William F. Owen Jr, MD

      Affiliations

    • Office of the Chancellor, University of Tennessee, Health Sciences Center, Memphis, TN
    • ,
  • Wolfgang C. Winkelmayer, MD, ScD

      Affiliations

    • Division of Pharmacoepidemiology and Pharmacoeconomics, and Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
    • ,
  • P.J. Devereaux, MD

      Affiliations

    • Departments of Medicine and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
    • ,
  • Marcello Tonelli, MD, SM, FRCPC

      Affiliations

    • Institute of Health Economics, Edmonton, Departments of Medicine and Critical Care, University of Alberta, Alberta, Canada
    • Corresponding Author InformationAddress reprint requests to Marcello Tonelli, MD, SM, FRCPC, University of Alberta, Division of Nephrology and Immunology, 11-103C Clinical Science Bldg, 8440 112 St, Edmonton, Alberta T6B 2B7, Canada

Received 12 December 2005 ,Revised 21 March 2006

  • Image Result

    Hierarchy of study end points.

    Hierarchy of study end points.

  • Image Result

    Reasons for failure of surrogate end points. (A) The surrogate is not in the causal pathway of the disease process. (B) Of several causal pathways of disease, the intervention affects only the pathway

    Reasons for failure of surrogate end points. (A) The surrogate is not in the causal pathway of the disease process. (B) Of several causal pathways of disease, the intervention affects only the pathway mediated through the surrogate. (C) The surrogate is not in the pathway of the intervention’s effect or is insensitive to its effect. (D) The intervention has mechanisms of action independent of the disease process. Dotted lines, mechanisms of action that might exist. (Original source: Annals of Internal Medicine9; reprinted with permission from the American College of Physicians.)

  • Image Result
    Opportunity cost.

    Opportunity cost.

 Originally published online as doi:10.1053/j.ajkd.2006.03.044 on May 10, 2006.Support: None. Potential conflicts of interest: None.

PII: S0272-6386(06)00545-2

doi: 10.1053/j.ajkd.2006.03.044

American Journal of Kidney Diseases
Volume 48, Issue 1 , Pages 159-166 , July 2006

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