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

References 

  1. Temple R . A regulatory authority’s opinion about surrogate endpoints . In:  Nimmo WS ,  Tucker GT editor. Clinical Measurement in Drug Evaluation . New York, NY: Wiley; 1995, pp 3-23;
  2. US Department of Health and Human Services: FDA: The Nation’s Premier Consumer Health Protection Agency, in US Food and Drug Administration, 2004. Available at: http://www.fda.gov/oc/opacom/brochure/Healthbro.pdf FDA 01-1316. Accessed November 1, 2006
  3. US Department of Health and Human Services: Guidance for Industry: Fast Track Drug Development Programs—Designation, Development, and Application Review, in, Food and Drug Administration, 2004. Available at: http://www.fda.gov/cder/guidance/index.htm. Accessed November 1, 2006
  4. Chertow GM , Burke SK , Raggi P . Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients . Kidney Int . 2002;62:245–252
  5. Huybrechts KF , Caro JJ , Wilson DA , O’Brien JA . Health and economic consequences of sevelamer use for hyperphosphatemia in patients on hemodialysis . Value Health . 2005;8:549–561
  6. Huybrechts KF , Caro JJ , London GM . Modeling the implications of changes in vascular calcification in patients on hemodialysis . Kidney Int . 2005;67:1532–1538
  7. Block GA , Martin KJ , de Francisco AL , et al.   Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis . N Engl J Med . 2004;350:1516–1525
  8. Eknoyan G , Levin A , Levin NW . Bone metabolism and disease in chronic kidney disease . Am J Kidney Dis . 2003;42:1–201
  9. Fleming TR , DeMets DL . Surrogate end points in clinical trials (Are we being misled?) . Ann Intern Med . 1996;125:605–613
  10. Taylor JM , Wang Y . Surrogate markers and joint models for longitudinal and survival data . Control Clin Trials . 2002;23:626–634
  11. Lin DY , Fleming TR , De Gruttola V . Estimating the proportion of treatment effect explained by a surrogate marker . Stat Med . 1997;16:1515–1527
  12. Chen C , Wang H , Snapinn SM . Proportion of treatment effect (PTE) explained by a surrogate marker . Stat Med . 2003;22:3449–3459
  13. Prentice RL . Surrogate endpoints in clinical trials (Definition and operational criteria) . Stat Med . 1989;8:431–440
  14. Hughes MD . Evaluating surrogate endpoints . Control Clin Trials . 2002;23:703–707
  15. Burzykowski T , Molenberghs G , Buyse M . The Evaluation of Surrogate Endpoints . New York: Springer; 2005;
  16. Riggs BL , Hodgson SF , O’Fallon WM , et al.   Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis . N Engl J Med . 1990;322:802–809
  17. Biomarker Definitions Working Group: Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework . Clin Pharmacol Ther . 2001;69:89–95
  18. Psaty BM , Weiss NS , Furberg CD , et al.   Surrogate end points, health outcomes, and the drug-approval process for the treatment of risk factors for cardiovascular disease . JAMA . 1999;282:786–790
  19. Pratt CM , Moye LA . The Cardiac Arrhythmia Suppression Trial (Background, interim results and implications) . Am J Cardiol . 1990;65:20B–29B
  20. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators . Preliminary report (Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction) . N Engl J Med . 1989;321:406–412
  21. Moore T . Excess Mortality Estimates. Deadly Medicine: Why Tens of Thousands of Heart Patients Died in America’s Worst Drug Disaster . New York, NY: Simon & Schuster; 1995;
  22. Stampfer MJ , Colditz GA . Estrogen replacement therapy and coronary heart disease (A quantitative assessment of the epidemiologic evidence) . Prev Med . 1991;20:47–63
  23. Grady D , Rueben S , Pettiti D . Hormone therapy to prevent disease and prolong life in postmenopausal women . Ann Intern Med . 1992;117:1016–1037
  24. Hulley S , Grady D , Bush T , et al.  Heart and Estrogen/progestin Replacement Study (HERS) Research Group   Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women . JAMA . 1998;280:605–613
  25. Rossouw JE , Anderson GL , Prentice RL , et al.   Risks and benefits of estrogen plus progestin in healthy postmenopausal women (Principal results from the Women’s Health Initiative randomized controlled trial) . JAMA . 2002;288:321–333
  26. Strippoli GF , Craig JC , Schena FP . The number, quality, and coverage of randomized controlled trials in nephrology . J Am Soc Nephrol . 2004;15:411–419
  27. Wright JT , Bakris G , Greene T , et al.   Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease (Results from the AASK Trial) . JAMA . 2002;288:2421–2431
  28. Eknoyan G , Hostetter T , Bakris GL , et al.   Proteinuria and other markers of chronic kidney disease (A position statement of the National Kidney Foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)) . Am J Kidney Dis . 2003;42:617–622
  29. Ruggenenti P , Perna A , Loriga G , et al.   Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2) (Multicentre, randomised controlled trial) . Lancet . 2005;365:939–946
  30. De Jong PE , de Zeeuw D . Renoprotective therapy (Is it blood pressure or albuminuria that matters?) . Lancet . 2005;365:913–914
  31. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) . Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy . Lancet . 1997;349:1857–1863
  32. Klahr S , Levey AS , Beck GJ , et al.  Modification of Diet in Renal Disease Study Group   The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease . N Engl J Med . 1994;330:877–884
  33. Ravid M , Lang R , Rachmani R , Lishner M . Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study . Arch Intern Med . 1996;156:286–289
  34. Jacobsen P , Andersen S , Rossing K , Jensen BR , Parving HH . Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy . Kidney Int . 2003;63:1874–1880
  35. Rossing K , Schjoedt KJ , Jensen BR , Boomsma F , Parving HH . Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria . Kidney Int . 2005;68:1190–1198
  36. Jacobsen P , Andersen S , Jensen BR , Parving HH . Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy . J Am Soc Nephrol . 2003;14:992–999
  37. Suki WN , Zabeneh R , Cangiano J , et al.   The DCOR Trial (A prospective randomized trial assessing the impact on outcomes of sevelamer in dialysis patients) . J Am Soc Nephrol . 2005;16(suppl):S281A; (abstr)
  38. Cunningham J , Danese M , Olson K , Klassen P , Chertow GM . Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism . Kidney Int . 2005;68:1793–1800
  39. Manns B , Taub K , Donaldson C . Economic evaluation and end-stage renal disease (From basics to bedside) . Am J Kidney Dis . 2000;36:12–28
  40. National Kidney Foundation . K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease . Am J Kidney Dis . 2003;42(suppl 3):S1–S201

 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

Article Tools

* Image Usage & Resolution