Skip to main content
Log in

Ethics and research in critical care

  • Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Background

The past few years have witnessed several controversies regarding the ethics of conducting research involving critically ill patients, and such research is ethically challenging.

Discussion

Research ethics is a changing field, one that is influenced by empirical data, contemporary events, and new ideas regarding aspects of clinical trial design and protection of human subjects. We describe recent thoughts regarding several aspects of research ethics in the critical care context.

Conclusion

The ability of the research community to conduct research ethically and to maintain public trust would benefit from heightened awareness to the principles and requirements that govern such research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. 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. U.S. Government Printing Office, Washington

    Google Scholar 

  2. Emanuel EJ, Wendler D, Grady C (2000) What makes clinical research ethical? JAMA 283:2701–2711

    Article  PubMed  CAS  Google Scholar 

  3. Anonymous (2001) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Off J Eur Communities L121:33–44

    Google Scholar 

  4. London AJ, Kadane JB (2002) Placebos that harm: sham surgery controls in clinical trials. Stat Methods Med Res 11:413–427

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Dreyfuss D (2005) Is it better to consent to an RCT or to care? Intensive Care Med 31:345–355

    Article  PubMed  Google Scholar 

  7. Concato J, Shah N, Horwitz RI (2000) Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 342:1887–1892

    Article  PubMed  CAS  Google Scholar 

  8. Mann H, Djulbegovic B (2003) Choosing a control intervention for a randomised clinical trial. BMC Med Res Methodol 3:7

    Article  PubMed  Google Scholar 

  9. Silverman HJ, Miller FG (2004) Control group selection in critical care randomized controlled trials evaluating interventional strategies: An ethical assessment. Crit Care Med 32:852–857

    Article  PubMed  Google Scholar 

  10. Miller FG, Silverman HJ (2004) The ethical relevance of the standard of care in the design of clinical trials. Am J Respir Crit Care Med 169:562–564

    Article  PubMed  Google Scholar 

  11. Parshuram CS, Kavanagh BP (2004) Positive clinical trials. Understand the control group before implementing the result. Am J Respir Crit Care Med 170:223–226

    Article  PubMed  Google Scholar 

  12. Gutierrez G, Palizas F, Doglio G, Wainsztein N, Gallesio A, Pacin J, Dubin A, Schiavi E, Jorge M, Pusajo J ea (1992) Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet 339:195–199

    Article  PubMed  CAS  Google Scholar 

  13. Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, Laporta DP, Viner S, Passerini L, Devitt H, Kirby A, Jacka M, Canadian Critical Care Clinical Trials Group (2003) A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 348:5–14

    Article  PubMed  Google Scholar 

  14. Richard C, Warszawski J, Anguel N, Deye N, Combes A, Barnoud D, Boulain T, Lefort Y, Fartoukh M, Baud F, Boyer A, Brocahrd L, Teboul JL, for the French Pulmonary Artery Catheter Study Group (2003) Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome. A randomized controlled trial. JAMA 290:2713–2720

    Article  PubMed  CAS  Google Scholar 

  15. Harvey S, Harrison DA, Singer M, Ashcroft J, Jones CM, Elbourme D, Brampton W, Williams D, Young DR, Rowan K, PAC-Man Study collaboration (2005) Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomized controlled trial. Lancet 366:472–477

    Article  PubMed  Google Scholar 

  16. SAFE Study Investigators (2004) A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 350:2247–2256

    Article  Google Scholar 

  17. Krishnan JA, Moore D, Roveson C, Rand CS, Fessler HE (2004) A prospective, controlled trial of a protocol-based strategy to discontinue mechanical ventilation. Am J Respir Crit Care Med 169:673–678

    Article  PubMed  Google Scholar 

  18. Randolph AG, Wjypij D, Venkataraman ST, Hanson JH, Gedeit rG, Meert KL, Luckett PM, Forbes P, Lilley M, Thompson J (2002) Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: a randomized controlled trial. JAMA 288:2561–2568

    Article  PubMed  Google Scholar 

  19. Ely EW, Baker AM, Duagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF (1996) Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 335:1864–1869

    Article  PubMed  CAS  Google Scholar 

  20. Anonymous (2004) The ethical conduct of clinical research involving critically ill patients in the United States and Canada. Am J Respir Crit Care Med 170:1375–1384

    Article  Google Scholar 

  21. NICE-SUGAR Study Investigators (2005) A multi-centre, open label, randomised controlled trial of two target ranges for glycaemic control in intensive care unit (ICU) patients. Availlable at: http://controlled-trialscom/isrctn/trial/ISRCTN0498275/0/04968275html, accessed 5 February 2006

    Google Scholar 

  22. 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 342:1301–1308

    Article  Google Scholar 

  23. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Fihlo G, Kariralla RA, Deheinzeline D, Munoz C, Oliveria R (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338:347–354

    Article  PubMed  CAS  Google Scholar 

  24. Van Den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367

    Article  PubMed  Google Scholar 

  25. Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C (2002) Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 166:1510–1514

    Article  PubMed  Google Scholar 

  26. Bellomo R (2005) Glycemic control in the intensive care unit: why we should wait for NICE-SUGAR. Mayo Clin Proc 80:1546–1548

    Article  PubMed  Google Scholar 

  27. Parshuram C, Kavanagh B (1983) Meta-analysis of tidal volumes in ARDS. Am J Respir Crit Care Med 167:798

    Google Scholar 

  28. Weijer C (2000) The ethical analysis of risk. J Law Med Ethics 28:344–361

    PubMed  CAS  Google Scholar 

  29. McRae AD, Weijer C (2002) Lessons from everyday lives: a moral justification for acute care research. Crit Care Med 30:1146–1151

    Article  PubMed  Google Scholar 

  30. National Bioethics Advisory Commission (2001) Ethical and policy issues in research involving human participants. U.S. Government Printing Office, Rockville

    Google Scholar 

  31. Freeman BD, Danner RL, Banks SM, Natanson C (2001) Safeguarding patients in clinical trials with high mortality rates. Am J Respir Crit Care Med 164:190–192

    PubMed  CAS  Google Scholar 

  32. Lemaire F, Brun-Buisson C (2000) Are institutional review boards effective in safe-guarding patients in intensive care units? Curr Opin Anaesthesiol 13:195–200

    Article  PubMed  CAS  Google Scholar 

  33. Karlawish JHT (2003) Research involving cognitively impaired adults. N Engl J Med 348:1289–1392

    Article  Google Scholar 

  34. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) Research involving children: report and recommendations. U.S. Department of Health, Education and Welfare, Washington

    Google Scholar 

  35. National Bioethics Advisory Commission (1998) Research involving persons with mental disorders that may affect decisionmaking capacity. U.S. Government Printing Office, Rockville

    Google Scholar 

  36. World Medical Association (2000) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. HIV Clin Trials 2001:92–95

    Google Scholar 

  37. Morin K, Rakatansky H, Riddick FA et al. (2002) Managing conflicts of interest in the conduct of clinical trials. JAMA 287:78–84

    Article  PubMed  Google Scholar 

  38. University of California Office of the President Office of Research (2002) Guidance on surrogate consent for research. Available at: http://www.llnl.gov/HumanSubjects/pdfs/surrogate.pdf; accessed 22 September 2003

  39. Saks ER (1999) Competency to decide on treatment and research. The MacArthur capacity instruments. In: National Bioethics Advisory Commission (ed) Research involving persons with mental disorders that may affect decisionmaking capacity,vol II. Commissioned papers. National Bioethics Advisory Commission, Rockville

    Google Scholar 

  40. Silverman HJ, Luce JM, Schwartz J (2004) Protecting subjects with decisional impairment in research. The need for a multifaceted approach. Am J Respir Crit Care Med 169:10–14

    Article  PubMed  Google Scholar 

  41. Keyserlingk EW, Kogan GK, Gauthier S (1995) Proposed guidelines for the participation of persons with dementia as research subjects. Perspect Biol Med 38:319–361

    PubMed  Google Scholar 

  42. Lidz WW, Appelbaum PS (2002) The therapeutic misconception. Problems and solutions. Med Care 40:V55–V63

    Article  PubMed  Google Scholar 

  43. Dresser R (2002) The ubiquity and utility of the therapeutic misconception. Soc Philos Policy Foundation 19:271–294

    Article  Google Scholar 

  44. Silverman HJ (1996) Ethical considerations of ensuring an informed and autonomous consent in research involving critically ill patients. Am J Respir Crit Care Med 154:582–586

    PubMed  CAS  Google Scholar 

  45. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (1997) Consolidated guideline on good clinical practice in the conduct of clinical trials on medicinal products for human use. Int Dig Health Legis 48:231–234

    Google Scholar 

  46. Silverman HJ, Hull SC, Sugarman J (2001) Variability among institutional review boards' decisions within the context of a multicenter trial. Crit Care Med 29:235–241

    Article  PubMed  CAS  Google Scholar 

  47. Advisory Committee on Human Radiation Experiments (1995) Final report. U.S. Government Printing Office, Washington

    Google Scholar 

  48. Silverman HJ, Luce JM, Lanken PN, Morris AH, Harabin AL, Oldmixon CF, Thompson BT, Bernard GR, for the NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network (2005) Recommendations for informed consent forms for critical care clinical trials. Crit Care Med 33:867–882

    Article  PubMed  Google Scholar 

  49. Estey A, Wilkin G, Dossetor J (1994) Are research subjects able to retain the information they are given during the consent process. Health Law Rev 3:37–41

    Google Scholar 

  50. Williams FF, French JK, White HD, for the HERO-2 consent substudy investigators (2003) Informed consent during the clinical emergency of acute myocardial infarction (HERO-2 consent substudy): a prospective observational study. Lancet 361:918–922

    Article  PubMed  Google Scholar 

  51. Schaeffer MH, Krantz DS, Wichman A, Masur H, Reed E, Vinicky JK (1996) The impact of disease severity on the informed consent process in clinical research. Am J Med 100:261–268

    Article  PubMed  CAS  Google Scholar 

  52. Appelbaum PS, Roth LH, Lidz CW, Benson P, Winslade W (1987) False hopes and best data: consent to research and the therapeutic misconception. Hastings Cent Rep 17:20–24

    PubMed  CAS  Google Scholar 

  53. Miller FG, Rosenstein DL (2003) The therapeutic orientation to clinical trials. N Engl J Med 348:1383–1386

    Article  PubMed  Google Scholar 

  54. Lemaire F (2004) Patient care versus research: does clinical research provide individual benefit to patients enrolled in trials. Curr Opin Crit Care 10:565–569

    Article  PubMed  Google Scholar 

  55. Appelbaum PS (2002) Clarifying the ethics of clinical research: a path toward avoiding the therapeutic misconception. Am J Bioethics 2:22–23

    Article  Google Scholar 

  56. Clemens JD, Frederik FP, van Loon L, Rao M, Sack DA, Ahmed F, Chakraborty J, Khan MR, Yunus M, Harris JR, Svennerholm AM et al. (1992) Nonparticipation as a determinant of adverse health outcomes in a field trial of oral cholera vaccines. Am J Epidemiol 135:865–874

    PubMed  CAS  Google Scholar 

  57. Peppercorn JM, Weeks JC, Cook EF, Joffe S (2004) Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review. Lancet 363:263–270

    Article  PubMed  Google Scholar 

  58. Hawkins JS, Emanuel EJ (2005) Clarifying confusions about coercion. Hastings Cent Rep 35:16–19

    PubMed  Google Scholar 

  59. Anonymous (2005) Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing of importation of such products. Official J Eur Union L91:13–19

    Google Scholar 

  60. Sulmasy DP, Terry PB, Weisman CS, Miller DJ, Stallings RY, Vettese MA, Haller KB (1998) The accuracy of substituted judgments in patients with terminal diagnoses. Ann Intern Med 128:621–629

    PubMed  CAS  Google Scholar 

  61. Coppolino M, Ackerson L (2001) Do surrogate decision makers provide accurate consent for intensive care research? Chest 119:603–612

    Article  PubMed  CAS  Google Scholar 

  62. Jones C, Skirrow P, Griffiths R, Humphris G, Ingleby S, Eddleston J, Waldmann C, Gager M (2004) Post-traumatic stress disorder-related symptoms in relatives of patients following intensive care. Intensive Care Med 30:456–460

    Article  PubMed  Google Scholar 

  63. Pochard F, Azoulay E, Chevret S, Lemaire F, Hubert P, Canoui P, Grassin M, Zittoun R, LeGall JR, Dhainaut JF, Schlemmer B, French FAMIRFA Group (2001) Symptoms of anxiety and depression in family members of intensive care unit patients: ethical hypothesis regarding decision-making capacity. Crit Care Med 29:1893–1897

    Article  PubMed  CAS  Google Scholar 

  64. United States Department of Health and Human Services (1996) Protection of human subjects: informed consent and waiver of informed consent requirements in certain emergency research. Final rules, 61. Fed Register 51500–51533

  65. Nichol G, Huszti E, Rokosh J, Dumbrell A, McGowan J, Becker L (2004) Impact of informed consent requirements on cardiac arrest research in the United States: exception from consent or from research? Resuscitation 62:3–23

    Article  PubMed  CAS  Google Scholar 

  66. Hiller KM, Haukoos JS, Heard K, Tashkin JS, Paradis NA (2005) Impact of the final rule on the rate of clinical cardiac arrest research in the United States. Acad Emerg Med 12:1091–1098

    Article  PubMed  Google Scholar 

  67. Lemaire F (2002) European Society of Intensive Care Medicine statement. Intensive Care Med 28:1218–1219

    Article  PubMed  CAS  Google Scholar 

  68. Lemaire F (2005) Waiving consent for emergency research. Eur J Clin Invest 35:287–289

    Article  PubMed  CAS  Google Scholar 

  69. Morse MA, Califf RM, Sugarman J (2001) Monitoring and ensuring safety during clinical research. JAMA 285:1201–1205

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Henry J. Silverman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Silverman, H.J., Lemaire, F. Ethics and research in critical care. Intensive Care Med 32, 1697–1705 (2006). https://doi.org/10.1007/s00134-006-0305-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-006-0305-4

Keywords

Navigation