Does random treatment assignment cause harm to research participants?

PLoS Medicine

Volumn 3, Issue 6, 2006, Pages 0800-0808

  Gross, Cary P ^a   Krumholz, Harlan M ^a,b   Van Wye, Gretchen ^a   Emanuel, Ezekiel J ^c   Wendler, David ^c  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b YALE CANCER CENTER   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLINICAL STUDY; CONTROLLED STUDY; HUMAN; MEDICAL LITERATURE; MEDICAL RESEARCH; MEDLINE; NON PARTICIPANT OBSERVATION; PARTICIPANT OBSERVATION; PUBLICATION; REVIEW; ARTICLE; CARDIOLOGY; FEMALE; GYNECOLOGY; HEALTH CARE QUALITY; META ANALYSIS; METHODOLOGY; OBSTETRICS; ONCOLOGY; PATIENT SELECTION; PREGNANCY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESEARCH SUBJECT; RISK ASSESSMENT; TREATMENT OUTCOME;

CARDIOLOGY; FEMALE; GYNECOLOGY; HUMANS; MEDICAL ONCOLOGY; OBSTETRICS; PATIENT SELECTION; PREGNANCY; QUALITY OF HEALTH CARE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH SUBJECTS; RISK ASSESSMENT; TREATMENT OUTCOME;

EID: 33745609518     PISSN: 15491277     EISSN: 15491676     Source Type: Journal    
DOI: 10.1371/journal.pmed.0030188     Document Type: Review

References (68)

1. 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.
2. Taylor KM, Margolese RG, Soskolne CL (1984) Physicians' reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer. N Engl J Med 310: 1363-1367.
3. Feinstein AR (1984) Current problems and future challenges in randomized clinical trials. Circulation 70: 767-774.
4. Abel U, Koch A (1999) The role of randomization in clinical studies: Myths and beliefs. J Clin Epidemiol 52: 487-497.
5. Kemeny MM, Peterson BL, Kornblith AB, Muss HB, Wheeler J, et al. (2003) Barriers to clinical trial participation by older women with breast cancer. J Clin Oncol 21: 2268-2275.
6. Jenkins V, Fallowfield L (2000) Reasons for accepting or declining to participate in randomized clinical trials for cancer therapy. Br J Cancer 82: 1783-1788.
7. Fallowfield L, Ratcliffe D, Souhami R (1997) Clinicians' attitudes to clinical trials of cancer therapy. Eur J Cancer 33: 2221-2229.
8. Taylor K, Feldstein M, Skeel R, Pandya K, Carbone P (1994) Fundamental dilemmas of the randomized clinical trial process: Results of a survey of 1737 Eastern Cooperative Oncology Group investigators. J Clin Oncol 12: 1796-1805.
9. Daugherty C, Ratain MJ, Grochowski E, Stocking C, Kodish E, et al. (1995) Perceptions of cancer patients and their physicians involved in phase I trials. J Clin Oncol 13: 1062-1072.
10. Joffe S, Weeks JC (2002) Views of American oncologists about the purposes of clinical trials. J Natl Cancer Inst 94: 1847-1853.
11. Yuval R, Halon DA, Merdler A, Khader N, Karkabi B, et al. (2000) Patient comprehension and reaction to participating in a double-blind randomized clinical trial (ISIS-4) in acute myocardial infarction. Arch Intern Med 160: 1142-1146.
12. Karjalainen S, Palva I (1989) Do treatment protocols improve end results? A study of survival of patients with multiple myeloma in Finland. BMJ 299: 1069-1072.
13. Davis S, Wright P, Schulman S, Hill L, Pikham R, et al. (1985) Participants in prospective randomized clinical trials for resected non-small lung cancer have improved survival compared with non-participants in such trials. Cancer 56: 1710-1718.
14. Marubini E, Mariani L, Salvadori B, Veronesi U, Saccozzi R, et al. (1996) Results of a breast-cancer-surgery trial compared with observational data from routine practice. Lancet 347: 1000-1003.
15. National Comprehensive Cancer Network (2006) NCCN clinical practice guidelines in oncology. Jenkintown (Pennsylvania): National Comprehensive Cancer Network. Available: http://www.nccn.org/professionals/physician_gls/ f_guidelines.asp. Accessed 4 April 2006.
16. Peppercorn J, 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.
17. Heiat A, Gross CP, Krumholz HM (2002) Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med 162: 1682-1688.
18. Kodish E, Eder M, Noll RB, Ruccione K, Lange B, et al. (2004) Communication of Randomization in Childhood Leukemia Trials. JAMA 291: 470-475.
19. Tunis SR, Stryer DB, Clancy CM (2003) Practical clinical trials: Increasing the value of clinical research for decision making in clinical and health policy. JAMA 290: 1624-1632.
20. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (2002) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288: 2981-2997.
21. Cannon CP, McCabe CH, Belder R, Breen J, Braunwald E (2002) Design of the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT)-TIMI 22 trial. Am J Cardiol 89: 860-861.
22. Kolata G (2004) Medicare covering new treatments, but with a catch. New York Times; Sect A: 1.
23. Olschewski M, Scheurlen H (1985) Comprehensive cohort study: An alternative to randomised consent. Methods Inf Med 24: 131-134.
24. Feit F, Brooks M, Sopko G, Keller N, Rosen A, et al. (2000) Long-term clinical outcome in the Bypass Angioplasty Revascularization Investigation Registry. Circulation 101: 2795-2802.
25. Bijker N, Peterse JL, Fentiman IS, Julien JP, Hart AA, et al. (2002) Effects of patient selection on the applicability of results from a randomised clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS. Br J Cancer 87: 615-620.
26. SAS Institute (2000) SAS/STAT, version 8.1 [computer program]. Cary (North Carolina): SAS Institute.
27. Marcus S (1997) Assessing non-consent bias with parallel randomized and nonrandomized clinical trials. J Clin Epidemiol 50: 823-828.
28. Paradise JL, Bluestone CD, Rogers KD, Taylor FH, Colborn DK, et al. (1990) Efficacy of adenoidectomy for recurrent otitis media in children previously treated with tympanostomy-tube placement. Results of parallel randomized and nonrandomized trials. JAMA 263: 2066-2073.
29. Melchart D, Steger HG, Linde K, Makarian K, Hatahet Z, et al. (2002) Integrating patient preferences in clinical trials: A pilot study of acupuncture versus midazolam for gastroscopy. J Altern Complement Med 8: 265-274.
30. Blichert-Toft M, Brincker H, Andersen JA, Andersen KW, Axelsson CK, et al. (1988) A Danish randomized trial comparing breast-preserving therapy with mastectomy in mammary carcinoma. Preliminary results. Acta Oncol 27: 671-677.
31. Antman K, Amato D, Wood W, Carson J, Suit H, et al. (1985) Selection bias in clinical trials. J Clin Oncol 3: 1142-1147.
32. Krzyzanowska MK, Pintilie M, Tannock IF (2003) Factors associated with failure to publish large randomized trials presented at an oncology meeting. JAMA 290: 495-501.
33. Weijer C (1999) Selecting subjects for participation in clinical research: One sphere of justice. J Med Ethics 25: 31-36.
34. United States Public Law 103-43 (1993 June 10) NIH Revitalization Act of 1993, Subtitle B, Section 131-133.
35. National Cancer Institute (2003) Age alone should not prevent older patients from enrolling in clinical trials. Bethesda (Maryland): National Cancer Institute. Available: http://www.cancer.gov/clinicaltrials/developments/age-as- barrier1005. Accessed 20 April 2006.
36. Stallings FL, Ford ME, Simpson NK, Fouad M, Jernigan JC, et al. (2000) Black participation in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control Clin Trials 21: 379S-389S.
37. Kolata G, Eichenwald (1999) Group of insurers to pay for experimental cancer therapy. New York Times; Sect C: 1, 9.
38. ECRI (2002 February) Should I enter a clinical trial? A patient reference guide for adults with a serious or life-threatening illness. Plymouth Meeting (Pennsylvania): ECRI. Available: http://www.ecri.org/Patient_-Information/ Patient_Reference_Guide/prg.pdf. Accessed 4 April 2006.
39. Braunholtz DA, Edwards SJ, Lilford RJ (2001) Are randomized clinical trials good for us (in the short term)? Evidence for a "trial effect". J Clin Epidemiol 54: 217-224.
40. Joffe S, Cook EF, Cleary PD, Clark JW, Weeks JC (2001) Quality of informed consent in cancer clinical trials: A cross-sectional survey. Lancet 358: 1772-1777.
41. Taub HA, Baker MT, Sturr JF (1986) Informed consent for research. Effects of readability, patient age, and education. J Am Geriatr Soc 34: 601-606.
42. Dunn LB, Lindamer LA, Palmer BW, Golshan S, Schneiderman LJ, et al. (2002) Improving understanding of research consent in middle-aged and elderly patients with psychotic disorders. Am J Geriatr Psychiatry 10: 142-150.
43. Lidz CW, Appelbaum PS, Grisso T, Renaud M (2004) Therapeutic misconception and the appreciation of risks in clinical trials. Soc Sci Med 58: 1689-1697.
44. Sreenivasan G (2003) Does informed consent to research require comprehension? Lancet 362: 2016-2018.
45. McPherson K, Britton A (1999) The impact of patient preferences on the interpretation of randomised controlled trials. Eur J Cancer 35: 1598-1602.
46. King M, Nazareth I, Lampe F, Bower P, Chandler M, et al. (2005) Impact of participant and physician intervention preferences on randomized trials: A systematic review. JAMA 293: 1089-1099.
47. Wendler D,, Kington R,, Madans J,, Wye GV, Christ-Schmidt H, et al. (2006) Are racial and ethnic minorities less willing to participate in health research? PLoS Med 3: e19. DOI: 10.1371/journal.pmed.0030019
48. Fleming I (1990) Clinical trials for cancer patients: The community practicing physician's perspective. Cancer 65: 2388-2390.
49. Foley J, Moertel C (1991) Improving accrual into cancer clinical trials. J Cancer Educ 6: 165-173.
50. Hallstrom A, Friedman L, Denes P, Rizo-Patron C, Morris M (2003) Do arrhythmia patients improve survival by participating in randomized clinical trials? Observations from the Cardiac Arrhythmia Suppression Trial (CAST) and the Antiarrhythmics Versus Implantable Defibrillators Trial (AVID). Control Clin Trials 24: 341-352.
51. King SB 3rd, Barnhart HX, Kosinski AS, Weintraub WS, Lembo NJ, et al. (1997) Angioplasty or surgery for multivessel coronary artery disease: Comparison of eligible registry and randomized patients in the EAST trial and influence of treatment selection on outcomes. Am J Cardiol 79: 1453-1459.
52. Cooper KG, Grant AM, Garratt AM (1997) The impact of using a partially randomised patient preference design when evaluating alternative managements for heavy menstrual bleeding. Br J Obstet Gynaecol 104: 1367-1373.
53. Chilvers C, Dewey M, Fielding K, Gretton V, Miller P, et al. (2001) Antidepressant drugs and generic counselling for treatment of major depression in primary care: Randomised trial with patient preference arms. BMJ 322: 772-775.
54. Bain C, Cooper KG, Parkin DE (2001) A partially randomized patient preference trial of microwave endometrial ablation using local anaesthesia and intravenous sedation or general anaesthesia: A pilot study. Gynaecol Endosc 10: 223-228.
55. CASS Principal Investigators and their associates (1984) Coronary Artery Surgery Study (CASS): A randomized trial of coronary artery bypass surgery. Comparability of entry characteristics and survival in randomized patients and nonrandomized patients meeting randomization criteria. J Am Coll Cardiol 3: 114-128.
56. Paradise JL, Bluestone CD, Bachman RZ, Colborn DK, Bernard BS, et al. (1984) Efficacy of tonsillectomy for recurrent throat infection in severely affected children. Results of parallel randomized and nonrandomized clinical trials. N Engl J Med 310: 674-683.
57. Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, et al. (1986) The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 314: 1600-1606.
58. Henshaw RC, Naji SA, Russell IT, Templeton AA (1993) Comparison of medical abortion with surgical vacuum aspiration: Women's preferences and acceptability of treatment. BMJ 307: 714-717.
59. Nicolaides K, Brizot Mde L, Patel F, Snijders R (1994) Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10-13 weeks' gestation. Lancet 344: 435-439.
60. McKay JR, Alterman AI, McLellan AT, Snider EC, O'Brien CP (1995) Effect of random versus nonrandom assignment in a comparison of inpatient and day hospital rehabilitation for male alcoholics. J Consult Clin Psychol 63: 70-78.
61. Schmoor C, Olschewski M, Schumacher M (1996) Randomized and non-randomized patients in clinical trials: Experiences with comprehensive cohort studies. Stat Med 15: 263-271.
62. de C Williams AC, Nicholas MK, Richardson PH, Pither CE, Fernandes J (1999) Generalizing from a controlled trial: The effects of patient preference versus randomization on the outcome of inpatient versus outpatient chronic pain management. Pain 83: 57-65.
63. Urban P, Stauffer JC, Bleed D, Khatchatrian N, Amann W, et al. (1999) A randomized evaluation of early revascularization to treat shock complicating acute myocardial infarction. The (Swiss) Multicenter Trial of Angioplasty for Shock - (S)MASH. Eur Heart J 20: 1030-1038.
64. Mosekilde L, Beck-Nielsen H, Sorensen OH, Nielsen SP, Charles P, et al. (2000) Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - Results of the Danish Osteoporosis Prevention Study. Maturitas 36: 181-193.
65. Rovers MM, Straatman H, Ingels K, van der Wilt GJ, van den Broek P, et al. (2001) Generalizability of trial results based on randomized versus nonrandomized allocation of OME infants to ventilation tubes or watchful waiting. J Clin Epidemiol 54: 789-794.
66. Wieringa-de Waard M, Vos J, Bonsel GJ, Bindels PJ, Ankum WM (2002) Management of miscarriage: A randomized controlled trial of expectant management versus surgical evacuation. Hum Reprod 17: 2445-2450.
67. Kerry S, Hilton S, Dundas D, Rink E, Oakeshott P (2002) Radiography for low back pain: A randomised controlled trial and observational study in primary care. Bri J Gen Pract 52: 469-474.
68. Kim SG, Hallstrom A, Love JC, Rosenberg Y, Powell J, et al. (1997) Comparison of clinical characteristics and frequency of implantable defibrillator use between randomized patients in the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial and nonrandomized registry patients. Am J Cardiol 80: 454-457.