Equipoise and the dilemma of randomized clinical trials

New England Journal of Medicine

Volumn 364, Issue 5, 2011, Pages 476-480

  Miller, Franklin G ^a   Joffe, Steven ^b,c  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DACARBAZINE; PLX 4032;

ADVERSE OUTCOME; ANALGESIA; BONE MARROW TRANSPLANTATION; BREAST CANCER; CLINICAL RESEARCH; COMMUNITY; COST EFFECTIVENESS ANALYSIS; DOCTOR PATIENT RELATION; EQUIPOISE; EVIDENCE BASED MEDICINE; FOOD AND DRUG ADMINISTRATION; HEALTH CARE COST; HEALTH CARE POLICY; HORMONE SUBSTITUTION; HUMAN; MEDICAL DECISION MAKING; MELANOMA; MORTALITY; PATIENT CARE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK BENEFIT ANALYSIS;

EID: 79551529835     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMsb1011301     Document Type: Review

References (35)

1. Marquis D. Leaving therapy to chance. Hastings Cent Rep 1983;13(4):40-7.
2. Gifford F. The conflict between randomized clinical trials and the therapeutic obligation. J Med Philos 1986;11:347-66.
3. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141-5.
4. Miller FG, Rosenstein DL. The therapeutic orientation to clinical trials. N Engl J Med 2003;348:1383-6.
5. Miller FG, Brody H. A critique of clinical equipoise: therapeutic misconception in the ethics of clinical trials. Hastings Cent Rep 2003;33(3):19-28.
6. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo - the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781-8.
7. Stadtmauer EA, O'Neill A, Goldstein LJ, et al. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med 2000;342:1069-76.
8. Moseley JB, O'Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002;347:81-8.
9. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.
10. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349:523-34.
11. Rettig RA, Jacobson PD, Farquhar CM, Aubry WM. False hope: bone marrow transplantation for breast cancer. Oxford, England: Oxford University Press, 2007.
12. Miller FG, Joffe S. Benefit in phase 1 oncology trials: therapeutic misconception or reasonable treatment option? Clin Trials 2008;5:617-23.
13. Pazdur R. Response rates, survival, and chemotherapy trials. J Natl Cancer Inst 2000;92:1552-3.
14. Buyse M, Thirion P, Carlson RW, Burzykowski T, Molenberghs G, Piedbois P. Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Lancet 2000;356:373-8.
15. Shanafelt TD, Loprinzi C, Marks R, Novotny P, Sloan J. Are chemotherapy response rates related to treatment-induced survival prolongations in patients with advanced cancer? J Clin Oncol 2004;22:1966-74.
16. Johnson KR, Ringland C, Stokes BJ, et al. Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis. Lancet Oncol 2006;7:741-6.
17. Tang PA, Bentzen SM, Chen EX, Siu LL. Surrogate end points for median overall survival in metastatic colorectal cancer: literature-based analysis from 39 randomized controlled trials of first-line chemotherapy. J Clin Oncol 2007;25:4562-8.
18. Bruzzi P, Del Mastro L, Sormani MP, et al. Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients. J Clin Oncol 2005; 23:5117-25.
19. Gifford F. Community-equipoise and the ethics of randomized clinical trials. Bioethics 1995;9:127-48.
20. Buchanan D, Miller FG. Principles of early stopping of randomized trials for efficacy: a critique of equipoise and an alternative nonexploitation ethical framework. Kennedy Inst Ethics J 2005;15:161-78.
21. Montori VM, Devereaux PJ, Adhikari NK, et al. Randomized trials stopped early for benefit: a systematic review. JAMA 2005;294:2203-9.
22. Bassler D, Briel M, Montori VM, et al. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 2010;303: 1180-7.
23. Wilcox RA, Djulbegovic B, Moffitt HL, Guyatt GH, Montori VM. Randomized trials in oncology stopped early for benefit. J Clin Oncol 2008;26:18-9.
24. Lui P, Cashin R, Machado M, Hemels M, Corey-Lisle PK, Einarson TR. Treatments for metastatic melanoma: synthesis of evidence from randomized trials. Cancer Treat Rev 2007;33:665-80.
25. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363:809-19.
26. Livingstone E, Zimmer L, Piel S, Schadendorf D. PLX4032: does it keep its promise for metastatic melanoma treatment? Expert Opin Investig Drugs 2010;19:1439-49.
27. Harmon A. New drugs stir debate on rules of clinical trials. New York Times. September 18, 2010:A1.
28. Joffe S, Miller FG. Bench to bedside: mapping the moral terrain of clinical research. Hastings Cent Rep 2008;38(2):30-42.
29. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000;283:2701-11.
30. Mishra R. Placebos break taboo in cancer drug tests: study seeks hope for desperately ill. Boston Globe. July 4, 2004:A1.
31. Tsimberidou A-M, Braiteh F, Stewart DJ, Kurzrock R. Ultimate fate of oncology drugs approved by the US Food and Drug Administration without a randomized trial. J Clin Oncol 2009; 27:6243-50.
32. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348:2609-17.
33. Einhorn LH, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 1977;87:293-8.
34. Berenson A. A cancer drug shows promise, at a price that many can't pay. New York Times. February 15, 2006.
35. Dedes KJ, Matter-Walstra K, Schwenkglenks M, et al. Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: an economic evaluation. Eur J Cancer 2009;45:1397-406.