The continuing unethical use of placebo controls

New England Journal of Medicine

Volumn 331, Issue 6, 1994, Pages 394-398

  Rothman, Kenneth J ^a   Michels, Karin B ^b  

^a BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDEPRESSANT AGENT; ANTIHYPERTENSIVE AGENT; IVERMECTIN; ONDANSETRON; PLACEBO;

CLINICAL TRIAL; COMPARATIVE STUDY; CONGESTIVE HEART FAILURE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DECISION MAKING; DRUG APPROVAL; FOOD AND DRUG ADMINISTRATION; HUMAN; MEDICAL ETHICS; NOTE; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS;

DRUG THERAPY; ETHICS, MEDICAL; HUMANS; INFORMED CONSENT; PLACEBOS; RANDOMIZED CONTROLLED TRIALS; RESEARCH DESIGN; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 0028070548     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJM199408113310611     Document Type: Editorial

References (43)

1. Hill AB Medical ethics and controlled trials. BMJ 1963; 1: 1043-1049
2. Grodin MA. Historical origins of the Nuremberg Code. In: Annas GJ, Grodin MA, eds. The Nazi doctors and the Nuremberg Code: human rights in human experimentation. New York: Oxford University Press, 1992:121-44.
3. Appendix 3. In: Annas GJ, Grodin MA, eds. The Nazi doctors and the Nuremberg Code: human rights in human experimentation. New York: Oxford University Press, 1992:331-42.
4. Declaration of Helsinki IV, World Medical Association, 41st World Medical Assembly, Hong Kong, September 1989. In: Annas GJ, Grodin MA, eds. The Nazi doctors and the Nuremberg Code: human rights in human experimentation. New York: Oxford University Press, 1992:339-42.
5. Greene BM, Taylor HR, Cupp EW, Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis. N Engl J Med 1985; 313: 133-138
6. Tugwell P, Bombardier C, Gent M, Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis. Lancet 1990; 335: 1051-1055
7. Johnsen V, Borg G, Trang LE, Berg E, Brodin U Auranofin (SK&F) in early rheumatoid arthritis: results from a 24-month double-blind, placebo-controlled study: effect on clinical and biochemical assessments. Scand J Rheumatol 1989; 18: 251-260
8. Williams HJ, Ward JR, Dahl SL, A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis. Arthritis Rheum 1988; 31: 702-713
9. Trentham DE, Dynesius-Trentham RA, Orav EJ, Effects of oral administration of type II collagen on rheumatoid arthritis. Science 1993; 261: 1727-1730
10. Felson DT, Anderson JJ, Meenan RF The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis: results of two metaanalyses. Arthritis Rheum 1990; 33: 1449-1461
11. Rickels K, Amsterdam J, Clary C, Fox I, Schweizer E, Weise C The efficacy and safety of paroxetine compared with placebo in outpatients with major depression. J Clin Psychiatry 1992; 53: Suppl: 30-32
12. Kiev A A double-blind, placebo-controlled study of paroxetine in depressed outpatients. J Clin Psychiatry 1992; 53: Suppl: 27-29
13. Smith WT, Glaudin V A placebo-controlled trial of paroxetine in the treatment of major depression. J Clin Psychiatry 1991; 53: Suppl: 36-39
14. Fabre LF Buspirone in the management of major depression: a placebo-controlled comparison. J Clin Psychiatry 1990; 51: Suppl: 55-61
15. Amsterdam JD, Dunner DL, Fabre LF, Kiev A, Rush AJ, Goodman LI Double-blind placebo-controlled, fixed dose trial of minaprine in patients with major depression. Pharmacopsychiatry 1989; 22: 137-143
16. Silverstone T Moclobemide — placebo controlled trials. Int Clin Psychopharmacol 1993; 7: 133-136
17. Fabre LF. Double-blind multi-center study comparing the safety and efficacy of sertratine with placebo in major depression. Presented at the Fifth World Congress of Biological Psychiatry, Florence, Italy, June 1991. abstract.
18. Bowden CL, Brugger AM, Swann AC, Efficacy of divalproex vs lithium and placebo in the treatment of mania. JAMA 1994; 271: 918-924
19. Gralla RJ, Tyson LB, Kris MG, Clark RA The management of chemotherapy-induced nausea and vomiting. Med Clin North Am 1987; 71: 289-301
20. Cunningham D, Evans C, Gazet J-C, Comparison of antiemetic efficacy of domperidone, metoclopramide, and dexamethasone in patients receiving outpatient chemotherapy regimens. BMJ 1987; 295: 250-250
21. Cox R, Newman CE, Leyland MJ Metoclopramide in the reduction of nausea and vomiting associated with combined chemotherapy. Cancer Chemother Pharmacol 1982; 8: 133-135
22. Edge SB, Funkhouser WK, Berman A, High-dose oral and intravenous metoclopramide in doxorubicin/cyclophosphamide-induced emesis: a randomized double-blind study. Am J Clin Oncol 1987; 10: 257-263
23. Beck TM, Ciociola AA, Jones SE, Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. Ann Intern Med 1993; 118: 407-413
24. Gandara DR, Harvey WH, Monaghan GG, The delayed-emesis syndrome from cisplatin: phase III evaluation of ondansetron versus placebo. Semin Oncol 1992; 19: Suppl: 67-71
25. Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med 1990; 322: 810-816
26. Citron ML Placebos and principles: a trial of ondansetron. Ann Intern Med 1993; 118: 470-471
27. Braunwald E ACE inhibitors — a cornerstone of the treatment of heart failure. N Engl J Med 1991; 325: 351-353
28. Kelbaek H, Agner E, Wroblewski H, Vasehus Madsen P, Marving J Angiotensin converting enzyme inhibition at rest and during exercise in congestive heart failure. Eur Heart J 1993; 14: 692-695
29. Packer M, Narahara KA, Elkayam U, Double-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. J Am Coll Cardiol 1993; 22: 65-72
30. Cowley AJ, McEntegart DJ Placebo-controlled trial of flosequinan in moderate heart failure: the possible importance of aetiology and method of analysis in the interpretation of the results of heart failure trials. Int J Cardiol 1993; 38: 167-175
31. Svetkey LP, Brobyn R, Deedwania P, Graham RM, Morganroth J, Klotman PE Double-blind comparison of doxazosin, nadolol, and placebo in patients with mild-to-moderate hypertension. Curr Ther Res 1988; 43: 969-978
32. Torvik D, Madsbu HP Multicentre 12-week double-blind comparison of doxazosin, prazosin and placebo in patients with mild to moderate essential hypertension. Br J Clin Pharmacol 1986; 21: Suppl 1: 69S-75S
33. Carr AA, Bottini PB, Prisant LM, Once-daily verapamil in the treatment of mild-to-moderate hypertension: a double-blind placebo-controlled dose-ranging study. J Clin Pharmacol 1991; 31: 144-150
34. Code of Federal Regulations, Food and Drugs, 21. Parts 300 to 499. Revised as of April 1, 1993. Section 314.126. Washington, D.C.: Government Printing Office, 1987.
35. Guidelines for the clinical evaluation of anti-inflammatory and antirheumatic drugs. Washington, D.C.: Department of Health and Human Services, 1988.
36. Temple R Government viewpoint of clinical trials. Drug Inf J 1982; 10-17
37. Spriet A, Dupin-Spriet T, Simon P. Choice of the comparator: placebo or active drug? In: Methodology of clinical drug trials. 2nd ed. New York: Karger, 1994.
38. Salsburg DS The religion of statistics as practiced in medical journals. Am Stat 1985; 39: 220-223
39. Gardner MJ, Altman DG Confidence intervals rather than P values: estimation rather than hypothesis testing. BMJ 1986; 292: 746-750
40. Rothman KJ Significance questing. Ann Intern Med 1986; 105: 445-447
41. Walker AM Reporting the results of epidemiologic studies. Am J Public Health 1986; 76: 556-558
42. Savitz DA Is statistical significance testing useful in interpreting data? Reprod Toxicol 1993; 7: 95-100
43. Cassileth BR, Zupkis RV, Sutton-Smith K, March V Informed consent — why are its goals imperfectly realized? N Engl J Med 1980; 302: 896-900