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Ethical Issues in Clinical Trials

  • Chapter
Clinical Trials for the Treatment of Sepsis

Part of the book series: Update in Intensive Care and Emergency Medicine ((UICM,volume 19))

Abstract

Research on human beings is important and necessary for the common good of society. Human experimentation is essential for the expansion of scientific knowledge in order to prevent, treat and cure disease. Despite the value of medical research in saving lives and relieving pain, the use of humans for experimental purposes often meets with opposition [1]. Medical progress requires clinical trials to introduce beneficial treatments and prevent the introduction of non-useful or harmful therapies. It would be helpful if the lay public became aware of the importance of clinical trials and became more knowledgeable about them before they were asked to participate in them. In 1747, one of the earliest reported clinical trials was performed by Sir James Lind in sailors with scurvy [2]. The first randomized controlled trial in modern times which occurred after World War II was the treatment of pulmonary tuberculosis with streptomycin [3]. There are those who believe that experimentation on human beings takes place continually in every doctor’s office and that deliberate experimentation on a group of patients is merely an efficient way to collect and interpret data that would otherwise be lost [1]. Some physicians believe all therapies should be given as part of clinical trials. Clearly, modern clinical investigations are different than research done in the past.

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References

  1. Shinkin MB (1953) The problem of experimentation on human beings. 1. The research worker’s point of view. Science 117: 205–207

    Article  Google Scholar 

  2. Thomas DP (1969) Experiment versus authority: James Lind and Benjamin Rush. N Engl J Med 281: 932–935

    Article  PubMed  CAS  Google Scholar 

  3. Medical Research Council (1948) Streptomycin treatment of pulmonary tuberculosis. Br J Med 2: 769–782

    Article  Google Scholar 

  4. Passamani E (1991) Clinical trials — Are they ethical? N Engl J Med 324: 1589–1592

    Article  PubMed  CAS  Google Scholar 

  5. Sackett DL (1982) The competing objectives of randomized trials. N Engl J Med 303: 1059–1069

    Article  Google Scholar 

  6. Hellman S, Hellman DS (1991) Of mice but not men. Problems of the randomized clinical trial. N Engl J Med 324: 1585–1589

    Article  PubMed  CAS  Google Scholar 

  7. Gehan EA, Freireich EJ (1974) Non-randomized controls in cancer clinical trials. N Engl J Med 290: 198–203

    Article  PubMed  CAS  Google Scholar 

  8. Byar DP, Schoenfeld DA, Green SB, et al (1990) Design considerations for AIDS trials. N Engl J Med 323: 1343–1347

    Article  PubMed  CAS  Google Scholar 

  9. Inman KJ, Martin CM, Sibbald WJ (1992) Design and conduct of clinical trials in critical care. J Crit Care 7: 118–128

    Article  Google Scholar 

  10. Eidelman LA, Sprung CL (1994) Why have new effective therapies for sepsis not been developed? Crit Care Med 22 (in press)

    Google Scholar 

  11. Beecher H (1966) Ethics and clinical research. N Engl J Med 274: 1354–1360

    Article  PubMed  CAS  Google Scholar 

  12. Brandt AM (1978) Racism and research: The case of the Tuskegee syphilis study. Hast Ctr Rep 8: 21–29

    Article  CAS  Google Scholar 

  13. Beauchamp TL, Childress JF (eds) (1983) Principles of biomedical ethics. 2nd ed. Oxford University Press, Oxford, pp 338–339

    Google Scholar 

  14. Beauchamp TL, Childress JF (eds) (1983) Principles of biomedical ethics. 2nd ed. Oxford University Press, Oxford, pp 339–343

    Google Scholar 

  15. National Research Act (1974) Pub Law 93-348, 42 USC 289L-3(a)

    Google Scholar 

  16. Beauchamp TL, Childress JF (eds) (1983) Principles of biomedical ethics. 2nd ed. Oxford University Press, Oxford, pp 59–220

    Google Scholar 

  17. National Commission for the protection of human subjects of biomedical and behavioral research (1979) The Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. Department of Health, Education and Welfare, Washington D.C., 5. DHEW publication no (05) 9–12065

    Google Scholar 

  18. Levine RJ, Cohen ED (1974) The Hawthorne effect. Clin Res 22: 111–112

    Google Scholar 

  19. Stiller C (1992) Survival of patients in clinical trials and at specialist centres. In: Williams CJ (ed) Introducing new treatments for cancer: Practical, ethical and legal problems. Wiley, Chichester, pp 119–136

    Google Scholar 

  20. Freedman B (1987) Equipoise and the ethics of clinical research. N Engl J Med 317: 141–145

    Article  PubMed  CAS  Google Scholar 

  21. Shaw LW, Chalmers TC (1970) Ethics in cooperative clinical trials. Ann NY Acad Sci 169: 487–494

    Article  PubMed  CAS  Google Scholar 

  22. Bone RC, Fisher CJ, Clemmer TP, et al (1987) A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317: 653–658

    Article  PubMed  CAS  Google Scholar 

  23. The Cardiac Arrhythmias Suppression Trial (CAST) Investigators (1989) Preliminary report: Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 321: 406–412

    Article  Google Scholar 

  24. Schafer A (1982) The ethics of the randomized clinical trial. N Engl J Med 307: 719–724

    Article  PubMed  CAS  Google Scholar 

  25. Sacks H, Kupfer S, Chalmers TC (1980) Are uncontrolled clinical studies ever justified? N Engl J Med 303: 1067 (Lett)

    Google Scholar 

  26. Hollenberg NK, Dzau VJ, Williams GH (1980) Are uncontrolled clinical studies ever justified? N Engl J Med 303: 1067 (Lett)

    Google Scholar 

  27. The Veterans Administration Systemic Sepsis Cooperative Study Group (1987) Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 317: 659–665

    Article  Google Scholar 

  28. Bone RC, Slotman G, Maunder R, et al (1989) Randomized double-blind, multicenter study of prostaglandin El in patients with the adult respiratory distress syndrome. Chest 96: 114–119

    Article  PubMed  CAS  Google Scholar 

  29. Sprung CL, Schein RMH (1986) Consent: Informed, implied or deferred. JAMA 256: 1891–1892

    Article  Google Scholar 

  30. Meisel A, Roth LH (1981) What we do and do not know about informed consent. JAMA 246: 2473–2477

    Article  PubMed  CAS  Google Scholar 

  31. Barry M (1988) Ethical considerations of human investigation in developing countries. N Engl J Med 319: 1083–1086

    Article  PubMed  CAS  Google Scholar 

  32. Angell M (1988) Ethical imperialism? Ethics in international collaborative clinical research. N Engl J Med 319: 1081–1083

    Article  PubMed  CAS  Google Scholar 

  33. Sprung CL, Winick BJ (1989) Informed consent in theory and practice: Legal and medical perspectives on the informed consent doctrine and a proposed reconceptualization. Crit Care Med 17: 1346–1354

    Article  PubMed  CAS  Google Scholar 

  34. Meisel A (1979) The exceptions to the informed consent doctrine: Striking a balance between competing values in medical decision-making. Wise Law Rev 1979: 413–488

    Google Scholar 

  35. Sprung CL, Peduzzi PN, Shatney CH, et al (1990) Impact of encephalopathy on mortality in the sepsis syndrome. Crit Care Med 18: 801–806

    Article  PubMed  CAS  Google Scholar 

  36. Zelen M (1979) A new design for randomized clinical trials. N Engl J Med 300: 1242–1245

    Article  PubMed  CAS  Google Scholar 

  37. Brewin TB (1982) Consent to randomised treatment. Lancet 2: 919–921

    Article  PubMed  CAS  Google Scholar 

  38. Nyman DJ, Sprung CL (1991) Ensuring informed consent: Essentials and specific exceptions. J Crit Illness 6: 89–96

    Google Scholar 

  39. Sprung CL (1990) Surrogate decision-making in critical care medicine. In: Lumb PD, Shoemaker WC (eds) Critical Care. State of the art 1990. Society of Critical Care Medicine, Fullerton, pp 367–377

    Google Scholar 

  40. Protection of human subjects (1973) 38 Fed Reg 31,739

    Google Scholar 

  41. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (1983) Patients who lack decision making capacity. In: Deciding to forego life-sustaining treatment: Ethical, medical and legal issues in treatment decisions. Government Printing Office, Washington, D.C., pp 121–170

    Google Scholar 

  42. Abramson NS, Meisel A, Safar P (1986) Deferred consent. A new approach for resus-citation research on comatose patients. JAMA 255: 2466–2471

    Article  PubMed  CAS  Google Scholar 

  43. Protection of human subjects (1983) 45 CFR § 46.111(a)

    Google Scholar 

  44. Protection of human subjects (1983) 45 CFR § 46.116(d)

    Google Scholar 

  45. Food and Drug Administration (1981) Protection of human subjects. 46 Fed Reg 8, 951

    Google Scholar 

  46. Park GR (1989) Ethical and moral difficulties with trials in critically ill patients. Intensive Care World 6: 11–12

    Google Scholar 

  47. Relman AS (1989) Economic incentives in clinical investigation. N Engl J Med 320: 933–934

    Article  PubMed  CAS  Google Scholar 

  48. Healy B, Campeau L, Gray R, et al (1989) Conflict-of-interest guidelines for a multi- center clinical trial of treatment after coronary-artery bypass-graft surgery. N Engl J Med 320: 949–951

    Article  PubMed  CAS  Google Scholar 

  49. O’Neill RT (1993) Some FDA perspectives on data monitoring in clinical trials in drug development. Statistics Med 12: 601–608

    Article  Google Scholar 

  50. Siegel JP, Stein KE, Zoon KC (1992) Anti-endotoxin monoclonal antibodies. N Engl J Med 327: 890–891

    Google Scholar 

  51. The SOLVD Investigators (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 325: 293–302

    Article  Google Scholar 

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Authors
  1. C. L. Sprung
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  2. L. A. Eidelman
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  3. D. J. Nyman
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Editor information

Editors and Affiliations

  1. Department of Critical Care, Victoria Hospital, 375 South Street, N6A 4G5, London, Ontario, Canada

    W. J. Sibbald

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© 1995 Springer-Verlag Berlin Heidelberg

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Sprung, C.L., Eidelman, L.A., Nyman, D.J. (1995). Ethical Issues in Clinical Trials. In: Vincent, JL., Sibbald, W.J. (eds) Clinical Trials for the Treatment of Sepsis. Update in Intensive Care and Emergency Medicine, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79224-3_25

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  • DOI: https://doi.org/10.1007/978-3-642-79224-3_25

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79226-7

  • Online ISBN: 978-3-642-79224-3

  • eBook Packages: Springer Book Archive

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