Beyond randomized, controlled trials

Current Opinion in Critical Care

Volumn 10, Issue 6, 2004, Pages 574-578

  Dreyfuss, Didier ^a,b  

^a HÔPITAL LOUIS MOURIER   (France)

^b Faculté Xavier Bichat   (France)

Author keywords

Controlled trials; Informed consent; Principles of ethics; Randomized

Indexed keywords

CLINICAL PRACTICE; CLINICAL RESEARCH; CRITICAL ILLNESS; EMERGENCY MEDICINE; EVIDENCE BASED MEDICINE; HUMAN; INFORMED CONSENT; INTENSIVE CARE; INTENSIVE CARE UNIT; MEDICAL ETHICS; MEDICAL LITERATURE; METHODOLOGY; PATIENT CARE; PHYSICIAN; PROTECTION; PUBLICATION; REVIEW;

EID: 10244234051     PISSN: 10705295     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.ccx.0000144763.88787.e8     Document Type: Review

References (69)

1. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research: Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, DC: U.S. Government Printing Office, 1979.
2. Beauchamp TL, Childress JF: Principles of Medical Ethics, 4th ed. New York: Oxford University Press, 1994.
3. Brower RG, Lanken PN, MacIntyre N, et al.: Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004, 351:327-336. This prospective study compared two PEEP levels during ventilation of patients with ARDS patients. A higher level was not associated with improved outcome compared with the lower level similar to that used in most surveys of mechanical ventilation of ARDS.
4. Esteban A, Anzueto A, Frutos F, et al.: Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 2002, 287:345-355.
5. 2O, a level that was used in one of the arms of the ALVEOLI trial [3asterisk inside a circle signasterisk inside a circle sign].
6. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000, 342:1301-1308.
7. Eichacker PQ, Gerstenberger EP, Banks SM, et al.: Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002, 166:1510-1514.
8. Dreyfuss D, Saumon G: Evidence-based medicine or fuzzy logic. What is best for ARDS management? Intensive Care Med 2002, 28:230-234.
9. Weinert CR, Gross CR, Marinelli WA: Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. Am J Respir Crit Care Med 2003, 167:1304-1309. This is an observational study on the impact of randomized trials on the ventilator management of ARDS. Tidal volume began to decrease before publication of the ARDS Network trial [6] and was not influenced by the results of this study.
10. Rubenfeld GD, Cooper C, Carter G, et al.: Barriers to providing lung-protective ventilation to patients with acute lung injury. Crit Care Med 2004, 32:1289-1293. This study discusses the reasons why clinicians seem not to adhere to the conclusions of the ARDS Network trial.
11. Young MP, Manning HL, Wilson DL, et al.: Ventilation of patients with acute lung injury and acute respiratory distress syndrome: has new evidence changed clinical practice? Crit Care Med 2004, 32:1260-1265. This study shows that tidal volume during ventilation of ARDS markedly decreased after publication of the ARDS Network trial. Indeed, it was 10 mL/kg measured body weight before publication of the trial and 8 mL/kg after.
12. D'Amico R, Pifferi S, Leonetti C, et al.: Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ 1998, 316:1275-1285.
13. de Jonge E, Schultz MJ, Spanjaard L, et al.: Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003, 362:1011-1016.
14. Vincent JL: Selective digestive decontamination: for everyone, everywhere? [editorial]. Lancet 2003, 362:1006-1007. This editorial suggests wide implementation of selective digestive decontamination in intensive care units, given the results of numerous RCTs and metaanalyses.
15. Kollef MH: Prevention of hospital-associated pneumonia and ventilator-associated pneumonia. Crit Care Med 2004, 32:1396-1405. This review warns against the use of selective digestive decontamination because of the risk of emergence of resistant bacteria
16. Cook DJ, Fuller HD, Guyatt GH, et al.: Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994, 330:377-381.
17. Ben-Menachem T, Fogel R, Patel RV, et al.: Prophylaxis for stress-related gastric hemorrhage in the medical intensive care unit. A randomized, controlled, single-blind study. Ann Intern Med 1994, 121:568-575.
18. Cook DJ, Reeve BK, Guyatt GH, et al.: Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA 1996, 275:308-314.
19. Messori A, Trippoli S, Vaiani M, et al.: Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ 2000, 321:1103-1106.
20. Vandenbroucke JP, de Craen AJ: Alternative medicine: a "mirror image" for scientific reasoning in conventional medicine. Ann Intern Med 2001, 135:507-513.
21. Lexchin J, Bero LA, Djulbegovic B, et al.: Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003, 326:1167-1170. This systematic review of pharmaceutical industry-sponsored research concludes that systematic bias favors products that are made by the company funding the research.
22. Steinbrook R: Public registration of clinical trials. N Engl J Med 2004, 351:315-317. This perspective deals with the importance of public registration of clinical trials to prevent selective reporting of results of some trials and concealing results of others.
23. Freeman BD, Danner RL, Banks SM, et al.: Safeguarding patients in clinical trials with high mortality rates. Am J Respir Crit Care Med 2001, 164:190-192.
24. Bernard GR, Vincent JL, Laterre PF, et al.: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001, 344:699-709.
25. Warren HS, Suffredini AF, Eichacker PQ, et al.: Risks and benefits of activated protein C treatment for severe sepsis. N Engl J Med 2002, 347:1027-1030.
26. Abraham E: Why immunomodulatory therapies have not worked in sepsis. Intensive Care Med 1999, 25:556-566.
27. Landry DW, Oliver JA: The pathogenesis of vasodilatory shock. N Engl J Med 2001, 345:588-595.
28. Luce JM: Is the concept of informed consent applicable to clinical research involving critically ill patients? Crit Care Med 2003, 31:S153-S160. Critical review of the informed consent process with special emphasis on the importance of surrogate consent to protect critically ill patients.
29. Bigatello LM, George E, Hurford WE: Ethical considerations for research in critically ill patients. Crit Care Med 2003, 31:S178-S181. This is an extensive discussion of the process of surrogate consent.
30. Coppolino M, Ackerson L: Do surrogate decision makers provide accurate consent for intensive care research? Chest 2001, 119:603-612.
31. Mazur DJ: Influence of the law on risk and informed consent. BMJ 2003, 327:731-734. This perspective on informed consent reminds us that its primary focus is disclosure of risk and discusses the role of legal cases in the evolution of the informed consent process.
32. Partridge AH, Winer EP: Informing clinical trial participants about study results. JAMA 2002, 288:363-365.
33. Pochard F, Azoulay E, Chevret S, et al.: Symptoms of anxiety and depression in family members of intensive care unit patients: ethical hypothesis regarding decision-making capacity. Crit Care Med 2001, 29:1893-1897.
34. Dreyfuss D: To consent or not to consent, that is (not) the (sole) question. "And there is nothing new under the sun". Kohelet (also known as Ecclesiastes), 1:9. Bible [editorial]. Intensive Care Med 2004, 30:180-182. This editorial contends that the problem of consent and its waiving is not the sole ethical issue in research in the critically ill patient.
35. Concato J, Horwitz RI: Beyond randomised versus observational studies [editorial]. Lancet 2004, 363:1660-1661. This editorial contends that well-conducted observational studies can provide the same level of internal validity as RCTs and have better external validity.
36. Silverman HJ, Miller FG: Control group selection in critical care randomized controlled trials evaluating interventional strategies: an ethical assessment. Crit Care Med 2004, 32:852-857. This review article is an ethical analysis of control group selection for critical care trials.
37. Steinbrook R: How best to ventilate? Trial design and patient safety in studies of the acute respiratory distress syndrome. N Engl J Med 2003, 348:1393-1401.
38. European Parliament: Directive 2001/20/EC of the European Parliament and of the Council. Official J Eur Communities 2001, L121:34-44.
39. Visser HK: Non-therapeutic research in the EU in adults incapable of giving consent? Lancet 2001, 357:818-819.
40. Singer EA, Mullner M: Implications of the EU directive on clinical trials for emergency medicine. BMJ 2002, 324:1169-1170.
41. Lemaire FJ: A European Directive for clinical research. Intensive Care Med 2003, 18:18. This paper provides an analysis of the potential consequences of the European directive on the conduct of research in critically ill patients with emphasis on the problem of research in emergent circumstances.
42. Silverman HJ, Druml C, Lemaire F, et al.: The European Union Directive and the protection of incapacitated subjects in research: an ethical analysis. Intensive Care Med 2004, 30:30. This is an analysis of ethical problems posed by the European directive with emphasis on the problem of consent during research in emergency circumstances.
43. Clifton GL, Knudson P, McDonald M: Waiver of consent in studies of acute brain injury. J Neurotrauma 2002, 19:1121-1126.
44. Annane D, Outin H, Fisch C, et al.: The effect of waiving consent on enrollment in a sepsis trial. Intensive Care Med 2004, 30:321-324. This paper reports an increase in the inclusion rate of patients in a trial on sepsis after consent for participation was waived.
45. Williams BF, French JK, White HD: Informed consent during the clinical emergency of acute myocardial infarction (HERO-2 consent substudy): a prospective observational study. Lancet 2003, 361:918-922. This study shows that consent in emergency situations was inappropriate for the needs of most patients enrolled in a trial on acute myocardial infarction, despite meeting regulatory requirements.
46. Bottiger BW, Bode C, Kern S, et al.: Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet 2001, 357:1583-1585.
47. Knottnerus JA, Dinant GJ: Medicine based evidence, a prerequisite for evidence based medicine. BMJ 1997, 315:1109-1110.
48. Thompson BT, Hayden D, Marthay MA, et al.: Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS. Chest 2001, 120:1622-1627.
49. Levy MM: PEEP in ARDS-how much is enough? [editorial]. N Engl J Med 2004, 351:389-391. This editorial discusses the methodologic strengths and weaknesses of the ALVEOLI trial [3asterisk inside a circle signasterisk inside a circle sign].
50. Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med 2000, 342:1878-1886.
51. Concato J, Shah N, Horwitz RI: Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000, 342:1887-1892.
52. Carome MA, Grodin MA, Dresser R, et al.: Is informed consent always necessary for randomized controlled trials? N Engl J Med 1999, 341:448-450.
53. Truog RD, Robinson W, Randolph A, et al.: Is informed consent always necessary for randomized, controlled trials? N Engl J Med 1999, 340:804-807.
54. Davis N, Pohlman A, Gehlbach B, et al.: Improving the process of informed consent in the critically ill. JAMA 2003, 289:1963-1968. This papers shows that the implementation of a universal consent form for invasive procedures routinely performed in critically ill patients improved both consent and comprehension.
55. Willison DJ, Keshavjee K, Nair K, et al.: Patients' consent preferences for research uses of information in electronic medical records: interview and survey data. BMJ 2003, 326:373. This survey shows that most patients are willing to allow information from their medical records to be used for research provided their consent is sought first.
56. Milberg J, Davis D, Steinberg K, Hudson L: Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA 1995, 273:306-309.
57. Jardin F, Fellahi JL, Beauchet A, et al.: Improved prognosis of acute respiratory distress syndrome 15 years on. Intensive Care Med 1999, 25:936-941.
58. Brochard L, Mancebo J, Tobin M: Searching for evidence: don't forget the foundations [editorial]. Intensive Care Med 2003, 29:2109-2111. This editorial highlights the fundamental importance of small observational trials for the improvement of management of critically ill patients.
59. Gattinoni L, Tognoni G, Pesenti A, et al.: Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001, 345:568-573.
60. Chatte G, Sab JM, Dubois JM, et al.: Prone position in mechanically ventilated patients with severe acute respiratory failure. Am J Respir Crit Care Med 1997, 155:473-478.
61. Faisy C, Guerot E, Diehl JL, et al.: Clinically significant gastrointestinal bleeding in critically ill patients with and without stress-ulcer prophylaxis. Intensive Care Med 2003, 29:1306-1313. This cohort study convincingly demonstrates the lack of effect of digestive stress ulcer bleeding prophylaxis.
62. Mello MM, Studdert DM, Brennan TA: The rise of litigation in human subjects research. Ann Intern Med 2003, 139:40-45. This is an analysis of the emergence of lawsuits against investigators, institutions, and institutional review boards during clinical research
63. Alliance for Human Research Protection. http://www.researchprotection. org. Accessed July 19, 2004.
64. Steinbrook R: Improving protection for research subjects. N Engl J Med 2002, 346:1425-1430.
65. Silverman HJ, Luce JM, Schwartz J: Protecting subjects with decisional impairment in research: the need for a multifaceted approach. Am J Respir Crit Care Med 2004, 169:10-14. This paper describes how protection of subjects during clinical research depends on multiple interdependent factors: federal government, states, and institutional review boards.
66. Koski G: Ethics, science, and oversight of critical care research: the Office for Human Research Protections. Am J Respir Crit Care Med 2004, 169:982-986. This paper thoroughly describes how the Office for Human Research Protections functions and its history, goals, and duties.
67. Slutsky AS, Lavery JV: Data safety and monitoring boards. N Engl J Med 2004, 350:1143-1147. This paper describes the role and functioning of data safety and monitoring boards and the scientific and ethical implications of their decisions.
68. Miller FG, Rosenstein DL: The therapeutic orientation to clinical trials. N Engl J Med 2003, 348:1383-1386. This article contends that a strict separation between care and research is needed to avoid therapeutic misconception.
69. Grunberg SM, Cefalu WT: The integral role of clinical research in clinical care. N Engl J Med 2003, 348:1386-1388. This article contends that a strict separation between care and research is not always feasible nor desirable.