Surrogate Measures of Patient-centered Outcomes in Critical Care

  • Rubenfeld G.D. 
Part of the Update in Intensive Care Medicine book series (UICMSOFT, volume 39)

Abstract

The ultimate goal of medicine is to improve health in ways that matter to patients. A variety of outcomes are important to patients: symptoms, quality of life, duration of life, quality of dying, the effect of their health care on their loved ones, and the cost of medical care. Because of the importance of these outcomes to patients they are referred to as ‘patient-centered’ outcomes. Ideally, chnicians will offer, insurers will pay for, and patients will have the opportunity to use treatments that have been shown to improve patient-centered outcomes. Patient-centered outcomes are dis- tinct from any number of chemical, physiologic, and radiographic variables that may be measured in clinical research. There are many reasons investigators choose to measure these important alternate or auxiliary measures. They often provide essential information about how a treatment works, about complications, and about the study population and subgroups. However, when one of these variables is used specifically as a substitute for a patient-centered outcome, it is referred to as a surrogate outcome variable. Other synonyms for these variables are interme- diate ox proxy outcome variables [2]. Common examples of surrogate outcomes are substituting blood pressure for survival in a study of antihypertensives, left ventricular function for quality of life in a study of therapy for congestive heart failure, and tumor size for survival in a study of cancer therapy.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Temple RJ (1995) A regulatory authority’s opinion about surrogate endpoints In: Nimmo WS, Tucker GT (eds) Clinical Measurement in Drug Evaluation J. Wiley, New York329Google Scholar
  2. 2.
    Fleming TR, DeMets DL (1996) Surrogate end points in clinical trials: are we being misled? Ann Intern Med 125605–613PubMedGoogle Scholar
  3. 3.
    Prentice RL (1989) Surrogate endpoints in Clinical trials: definition and operational criteria Stat Med 8431–440PubMedCrossRefGoogle Scholar
  4. 4.
    Fleming TR (1994) Surrogate markers in AIDS and cancer trials Stat Med 131423–1435PubMedCrossRefGoogle Scholar
  5. 5.
    Fleming TR, DeGruttola V, DeMets DL (1997) Surrogate endpoints AIDS Clin Rev 1997129–143Google Scholar
  6. 6.
    Hulley SB, Cummings SR (1988) Designing clinical research: an epidemiologic approach Williams & Wilkins, BaltimoreGoogle Scholar
  7. 7.
    The Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 3421301–1308CrossRefGoogle Scholar
  8. 8.
    Amato MB, Barbas CS, Medeiros DM, et al (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome N Engl J Med 338347–354PubMedCrossRefGoogle Scholar
  9. 9.
    Knaus WA, Harrell FE, Jr., LaBrecque JF, et al (1996) Use of predicted risk of mortality to evaluate the efficacy of anticytokine therapy in sepsis. The rhIL-Ira Phase III Sepsis Syndrome Study Group Crit Care Med 2446–56PubMedCrossRefGoogle Scholar
  10. 10.
    De Gruttola V, Fleming T, Lin DY, Coombs R (1997) Perspective: validating surrogate markers-are we being naive? I Infect Dis 175237–246CrossRefGoogle Scholar
  11. 11.
    Fleming TR (2000) Surrogate end points in cardiovascular disease trials Am Heart J 139S193–S196PubMedCrossRefGoogle Scholar
  12. 12.
    Fleming TR, Prentice RL, Pepe MS, Glidden D (1994) Surrogate and auxiliary endpoints in clinical trials, with potential applications in cancer and AIDS research Stat Med 13955–968PubMedCrossRefGoogle Scholar
  13. 13.
    De Gruttola VG, Clax P, DeMets DL, et al (2001) Considerations in the evaluation of surrogate endpoints in clinical trials, summary of a National Institutes of Health workshop Control Clin Trials 22485–502PubMedCrossRefGoogle Scholar
  14. 14.
    Echt DS, Liebson PR, Mitchell LB, et al (1991) Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial N Engl J Med 324781–788PubMedCrossRefGoogle Scholar
  15. 15.
    Advanced Colorectal Cancer Meta-Analysis Project (1992) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 10896–903Google Scholar
  16. 16.
    Psaty BM, Smith NL, Siscovick DS, et al (1997) Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis JAMA 277739–745PubMedCrossRefGoogle Scholar
  17. 17.
    Psaty BM, Weiss NS, Furberg CD, et al (1999) Surrogate end points, health outcomes, and the drug-approval process for the treatment of risk factors for cardiovascular disease JAMA 282786–790PubMedCrossRefGoogle Scholar
  18. 18.Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC (1990) Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials Circulation 821106–1116PubMedCrossRefGoogle Scholar
  19. 19.
    Sande MA, Carpenter CC, Cobbs CG, Holmes KK, Sanford JP (1993) Antiretroviral therapy for adult HIV-infected patients. Recommendations from a state-of-the-art conference. National Institute of Allergy and Infectious Diseases State-of-the-Art Panel on Anti-Retroviral Therapy for Adult HIV-infected Patients JAMA 2702583–2589PubMedCrossRefGoogle Scholar
  20. 20.
    Guidelines Committee, Society of Critical Care Medicine (1992) Guidelines for the definition of an intensivist and the practice of critical care medicine Crit Care Med 20540–542CrossRefGoogle Scholar
  21. 21.
    Dellinger RP, Zimmerman JL, Taylor RW, et al (1998) Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group Crit Care Med 2615–23PubMedCrossRefGoogle Scholar
  22. 22.
    Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C (1999) Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide Intensive Care Med 25911–919PubMedCrossRefGoogle Scholar
  23. 23.
    Gattinoni L, Tognoni G, Pesenti A, et al (2001) Effect of prone positioning on the survival of patients with acute respiratory failure N Engl J Med 345568–573PubMedCrossRefGoogle Scholar
  24. 24.
    Rennie M (1985) Muscle protein turnover and the wasting due to injury and disease Br Med Bull 41257–264PubMedGoogle Scholar
  25. 25.
    Gore DC, Honeycutt D, Jahoor F, Wolfe RR, Herndon DN (1991) Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients Arch Surg 12638–43PubMedCrossRefGoogle Scholar
  26. 26.
    Takala J, Ruokonen E, Webster NR, et al (1999) Increased mortality associated with growth hormone treatment in critically ill adults N Engl J Med 341785–792PubMedCrossRefGoogle Scholar
  27. 27.
    Sibbald WJ, Vincent JL (1995) Clinical Trials for the Treatment of Sepsis Springer-Verlag, HeidelbergGoogle Scholar
  28. 28.
    Zapol WM (1998) Nitric oxide inhalation in acute respiratory distress syndrome: it works, but can we prove it? Crit Care Med 262–3PubMedCrossRefGoogle Scholar
  29. 29.
    Angus DC, Musthafa AA, Clermont G, et al (2001) Quality-adjusted survival in the first year after the acute respiratory distress syndrome Am J Respir Crit Care Med 1631389–1394PubMedGoogle Scholar
  30. 30.
    Davidson TA, Rubenfeld GD, Caldwell ES, Hudson LD, Steinberg KP (1999) The Effect of Acute respiratory distress syndrome on long-term survival Am J Respir Crit Care Med 1601838–1842PubMedGoogle Scholar
  31. 31.
    Marshall JC (2000) Complexity, chaos, and incomprehensibility: parsing the biology of critical illness Crit Care Med 282646–2648PubMedCrossRefGoogle Scholar
  32. 32.
    Mant J, Hicks N (1995) Detecting differences in quality of care: the sensitivity of measures of process and outcome in treating acute myocardial infarction Br Med J 311793–796CrossRefGoogle Scholar
  33. 33.
    Curtis JR, Rubenfeld GD (2000) Managing Death in the ICU: The Transition from Cure to Comfort Oxford University Press, New YorkGoogle Scholar
  34. 34.
    Hansen-Flaschen JH (2000) Dyspnea in the ventilated patient: a call for patient-centered mechanical ventilation Respir Gare 451460–1464Google Scholar
  35. 35.
    Diehr P, Patrick D, Hedrick S, et al (1995) Including deaths when measuring health status over time Med Care 33 (Suppl 4)AS164–AS172PubMedGoogle Scholar
  36. 36.
    Heitjan DF (1999) Causal inference in a Clinical trial: a comparative example Control Clin Trials 20309–318PubMedCrossRefGoogle Scholar
  37. 37.
    Sullivan DF (1971) A single index of mortality and morbidity HSMHA Health Rep 86347–354PubMedCrossRefGoogle Scholar
  38. 38.
    McMahon RP, Harrell FE Jr (2001 ) Joint testing of mortality and a non-fatal outcome in clinical trials, Stat Med 201165–1172PubMedCrossRefGoogle Scholar
  39. 39.
    Hine LK, Laird N, Hewitt P, Chalmers TC (1989) Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction Arch Intern Med 1492694–2698PubMedCrossRefGoogle Scholar
  40. 40.
    Packer M, Carver JR, Rodeheffer RJ, et al (1991) Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group N Engl J Med 3251468–1475PubMedCrossRefGoogle Scholar
  41. 41.
    Law MR, Thompson SG, Wald NJ (1994) Assessing possible hazards of reducing serum cholesterol Br Med J 308373–379CrossRefGoogle Scholar
  42. 42.
    Hebert PC, Wells G, Blajchman MA, et al (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group N Engl I Med 340409–417CrossRefGoogle Scholar
  43. 43.
    Gattinoni L, Brazzi L, Pelosi P, et al (1995) A trial of goal-oriented hemodynamic therapy in critically ill patients. Sv02 Collaborative Group N Engl J Med 3331025–1032PubMedCrossRefGoogle Scholar
  44. 44.
    Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D (1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients N Engl J Med 3301717–1722PubMedCrossRefGoogle Scholar
  45. 45.
    Bernard GR, Wheeler AP, Russell JA, et al (1997) The effects of Ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group N Engl J Med 336912–918PubMedCrossRefGoogle Scholar
  46. 46.
    Fisher CJ, Jr., Dhainaut JF, Opal SM, et al (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-lra Sepsis Syndrome Study Group JAMA 2711836–1843PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Rubenfeld G.D. 
    • 1
  1. 1.Division of Pulmonary and Critical Care Medicine Harborview Medical CenterUniversity of WashingtonSeattleUSA

Personalised recommendations