Risk on trial: The interaction of innovation and risk in cancer clinical trials

The Risks of Medical Innovation: Risk Perception and Assessment in Historical Context

Volumn , Issue , 2005, Pages 204-219

  Keating, Peter ^a   Cambrosio, Alberto ^b  

^a UNIVERSITÉ DU QUÉBEC À MONTRÉAL   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84909210309     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.4324/9780203337493     Document Type: Chapter

References (69)

1. M.C.Christian et al., "A central institutional review board for multi-institutional trials", New England Journal of Medicine 346, 2002, 1405-8.
2. R.Steinbrook, "Protecting research subjects: the crisis at Johns Hopkins", New England Journal of Medicine 346, 2002, 716-20 (correction: 1678). The compound, in other words, was not a dmg to treat a condition but, rather, a substance designed to investigate a disease mechanism.
3. D.S.Greenberg, "Johns Hopkins research returns to normal", Lancet 359, 2001, 393.
4. On the events leading up to the creation of this Office, see Institute of Medicine, Preserving Public Trust: Accreditation and Human Research Protection Programs, Washington: National Academy of Sciences, 2001, pp. 29-32.
5. Steinbrook, "Protecting research subjects", pp. 716 and 1678. In 1998, Federal regulatory actions against Institutional Review Boards rose sharply from one in 1997 to fourteen in 1998;
6. see W.J.Burman et al., "Breaking the camel's back: multicenter clinical trials and local institutional review boards", Annals of Internal Medicine 134,2001, 152-7.
7. F.Rolleston and J.R.Miller, "Therapy or research: a need for precision", IRB 3(7), August/September 1981, 1-3.
8. Christian et al., "A central institutional review board", p. 1407.
9. Christian et al., "A central institutional review board", p. 1405.
10. S.J.Pocock, Clinical Trials: A Practical Approach, New York: John Wiley, 1983, p. 22.
11. See, e.g., S.Epstein, "Bodily differences and collective identities: the politics of gender and race in biomedical research in the United States", Body and Society, 10,2004, 183-203.
12. D. Schwartz and J.Lellouch, "Explanatory and pragmatic attitudes in therapeutic trials", Journal of Chronic Diseases 20, 1967, 637M8.
13. Schwartz and Lellouch, "Explanatory and pragmatic attitudes in therapeutic trials", p. 637.
14. P.Keating and A.Cambrosio, "From screening to clinical research: the cure of leukemia and the early development of the cooperative oncology groups, 1955-1966", Bulletin of the History of Medicine 76, 2002, 299-334.
15. A survey of members of the American Society of Clinical Oncology showed that many American oncologists believe that therapy constitutes the principle purpose of clinical trials; see S.Joffe and J.C.Weeks, "Views of American oncologists about the purposes of clinical trials", Journal of the National Cancer Institute 94, 2002, 1847-53.
16. The investigators that conducted the survey observed that this stance directly contradicted the principles of research ethics set out in the Belmont Report; see National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, "The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research", in J.Sugarman, A.C.Mastroianni and J.P.Kahn (eds), Ethics of Research with Human Subjects, Frederick, MD: University Publishing Group, 1998, pp. 9-30.
17. G.Burroughs Mider, "Annual report of the scientific director", National Cancer Institute vol. 1, 1959, p. 73.
18. E.A.Gehan, "The determination of the number of patients required in a preliminary and follow-up trial of a new chemotherapeutic agent", Journal of Chronic Diseases 13, 1961, 346-53.
19. See also E.A.Gehan and M.A.Schneiderman, "Historical and methodological developments in clinical trials at the National Cancer Institute", Statistics in Medicine 9, 1990, 871-80
20. and C.G.Zubrod, "Clinical trials in cancer patients: an introduction", Controlled Clinical Trials 3, 1982, 185-7.
21. For a brief history of clinical cancer trial statistics in general, see E.A.Gehan and N.A.Lemak, Statistics in Medical Research: Developments in Clinical Trials, New York: Plenum, 1994.
22. The "phase" terminology itself is not cast in stone: the FDA, together with the International Committee on Harmonization, have proposed new definitions of clinical trials according to the different purposes they suit rather than the different phases into which they fit; see Food and Drug Administration, "International conference on harmonization: guidance on general considerations for clinical trials", Federal Register 62(242), 1997, 66113-19.
23. National Institutes of Health, National Cancer Institute, Annual Report of Program Activities, vol. 1, 1960, p. 20.
24. National Institutes of Health, National Cancer Institute, Annual Report of Program Activities, vol. 1, 1960, p. 20.
25. S.K.Carter and P.S.Schein, "Clinical evaluation of new anticancer agents", in P.Calabresi, P.S.Schein and S.A.Rosenberg (eds) Medical Oncology: Basic Principles and Clinical Management of Cancer, New York: Macmillan, 1985, p. 393.
26. E.Frei III et al., "Studies of sequential and combination antimetabolite therapy in acute leukemia: 6-Mercaptopurine and Methotrexate", Blood 18, 1961, p. 451.
27. E.J.Freireich et al. (Acute Leukemia Group B), "The effect of 6-Mercaptopurine on the duration of steroid induced remissions in acute leukemia: a model for evaluation of other potentially useful therapies", Blood 21, 1963, 699-716; p. 711.
28. Report of the Cancer Clinical Investigation Review Committee on the "Cooperative Studies Workshop" held in Williamsburg Virginia, 20-23 October 1968. NCI Archives, p. 1.
29. Report of the Cancer Clinical Investigation Review Committee on the "Cooperative Studies Workshop" held in Williamsburg Virginia, 20-23 October 1968. NCI Archives, p. 1. This "new and broader charge" to the Committee had been made in February of 1968 by the National Advisory Cancer Council (NACC) Subcommittee on Diagnosis and Treatment and adopted by the NACC. Report of the Cancer Clinical Investigation Review Committee on the "Cooperative Studies Workshop" held in Williamsburg Virginia, 20-23 October 1968. NCI Archives, p. 2.
30. Report of the Cancer Clinical Investigation Review Committee on the "Cooperative Studies Workshop" held in Williamsburg Virginia, 20-23 October 1968. NCI Archives, p. 4.
31. Regarding single disease or organ groups, seven of the eight groups with pathology sections all added pathology to their Group in the period 1967-73. By 1977, within the groups as a whole, there was one pathologist (total: 400) for every four medical oncologists (total: 1,600), a not insignificant number. See V.Loeb, G.C.Lewis and J.Newall, "Cancer education", in B.Hoogstraten (ed.), Cancer Research: Impact of the Cooperative Groups, New York: Masson, 1980, 365-9; p. 368.
32. V.T.DeVita, "Human models of human diseases: breast cancer and the lymphomas", International Journal of Radiation Oncology, Biology, Physics 5, 1979, 1855-67.
33. "Cooperative group reorganization to be offered by DeVita at clinical trials review next March", The Cancer Letter 4(42), 1978, p. 2.
34. Similar charges were laid against the groups five years later by the former head of NCI's cancer centers program, John Yarbro; see "Feds short on money long on regs: Yarbro", The Cancer Letter 9(12), 1983, 2.
35. "New funding mechanisms-cooperative agreement consortium grant-proposed for clinical groups", The Cancer Letter 5(14), 1979, p. 4.
36. "New funding mechanisms-cooperative agreement consortium grant-proposed for clinical groups", The Cancer Letter 5(14), 1979, p. 3. In the "Minutes" of the Board of Counselors Meeting, these remarks were attributed to Vincent DeVita. See V.DeVita, "Opening remarks", Minutes, Board of Scientific Counselors, Clinical Trials Review, 26-27 March 1979, NCI Archives.
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38. S.Marsoni et al., "Clinical drug development", p. 79.
39. H.Beecher, "Ethics and clinical research", New England Journal of Medicine 274, 1966, 1354-60.
40. J.Heller, "Syphillis victims in US study went untreated for 40 years", New York Times 26 July 1972, Sec. A-l.
41. Ethics Oral History Project; Preliminary Findings, January 13, 1995, p. 12.
42. Institute of Medicine, Preserving Public Trust, p. 25.
43. D.J.Rothman, Strangers at the Bedside: A History of How Law and Bioethics Transformed Medical Decision Making, New York: Basic Books, 1991, p. 89.
44. Rothman, Strangers at the Bedside, p. 90.
45. See the retrospective remarks by one of the statistical innovators in this area, P.Armitage, "Theory and practice in medical statistics", Statistics in Medicine 20, 2001, 2537-48.
46. J.Crowley et al., "Data monitoring committees and early stopping guidelines: the Southwest Oncology Group experience", Statistics in Medicine 13, 1994, 1391-9; p. 1391.
47. For other groups and the NCI, see S.Green, T.Fleming and J.O'Fallon, "Policies for study monitoring and interim reporting of results", Journal of Clinical Oncology 7, 1987, 1477-84.
48. Crowley et al., "Data monitoring committees and early stopping guidelines", p. 1398.
49. S.K.Carter, "The potential lack of comparability between interim and final results of cancer clinical trials", Cancer Chemotherapy and Pharmacology 8, 1982, 1-2.
50. For the re-analysis of the Western Cancer Group trial data, see R.T.Chlebowski et al., "Survival of patients with metastatic breast cancer treated with either combination or sequential chemotherapy", Cancer Research 39, 1979, 4305-6;
51. for the ECOG data, see P.P.Carbone et al., "Chemotherapy of disseminated breast cancer: current status and prospects", Cancer 39 (Suppl.), 1977, 2916-22.
52. R.T.Chlebowski et al., "Factors influencing the interim interpretation of a breast cancer trial: danger of achieving the 'expected' result", Controlled Clinical Trials 2, 1980, 123-32; p.128.
53. M.Proschan, in "Panel discussion: scientific issues in data monitoring", Statistics in Medicine 12, 1993, 583-600; p. 586.
54. D.P.Harrington, in "Panel discussion: scientific issues in data monitoring", Statistics in Medicine 12, 1993, 583-600; p. 584.
55. Harrington, in "Panel discussion"; p. 584.
56. D.Bristow, in "Panel discussion; p. 584.
57. Harrington, in "Panel discussion"; p. 587.
58. R.Simon, in "Panel discussion", 521-5; p. 525.
59. W.Friedewald, in "Panel discussion", 583-600; p. 588.
60. "Panel discussion"; p. 594.
61. Harrington, in "Panel discussion"; p. 594.
62. M.A.Smith et al., "Role of independent data-monitoring committees in randomized clinical trials sponsored by the National Cancer Institute", Journal of Clinical Oncology 15, 1997, 2736-43; p. 2736.
63. For an angry reply to their argument, followed by the authors' rebuttal, see R.J.Wells, "Secrecy for data monitoring committees: inferior ethics, bad policy", Journal of Clinical Oncology 16, 1998, 390-1.
64. For a bioethical discussion of clinical equipoise, see B.Freedman, "Equipoise and the ethics of clinical research," New England Journal ofMedicine 317, 1987, 141-5.
65. Smith et al., "Role of independent data-monitoring committees", p. 2740.
66. L.Walters, "Data monitoring committees, the moral case for maximum feasible independence", Statistics in Medicine 12, 1993, 575-80, discussion 580-1.
67. For a criticism of this kind of statement, see R.J.Wells, P.S.Gartside and C.LMcHenry, "Ethical issues arising when interim data in clinical trials is restricted to independent data monitoring committees", IRB 22(1), January-February 2000, 7-11.
68. Smith et al., "Role of independent data-monitoring committees".
69. D.Harrington et al., "The case against independent monitoring committees", Statistics in Medicine 13, 1994, 1411-14; p. 1413.