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Competing or Complementary?: Ethical Considerations and the Quality of Randomized Trials

Published online by Cambridge University Press:  10 March 2009

Judith Lumley  and
Hilda Bastian
Judith Lumley
Affiliation:
University of Oxford
Hilda Bastian
Affiliation:
Consumer Advocate, Blackwood
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Abstract

The ethical principles of beneficence (doing the best for one's patients and clients), nonmaleficence (doing no harm), autonomy, justice, and equity, are positively associated with the quality of a trial rather than being opposed to it. Ethical considerations involve such important questions as appropriate design and documentation, participation rates, withdrawals or losses to follow-up, careful monitoring of safety and efficacy, timely completion, generalizability, and publication and dissemination of findings. When conflicts between ethical considerations and the trial's scientific quality do occur, the ethical considerations must be paramount.

Type
Special Section: The Quality of the Medical Evidence: Is It Good Enough?
Information
International Journal of Technology Assessment in Health Care , Volume 12 , Issue 2 , Spring 1996 , pp. 247 - 263
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

1.Allen, P. A., & Waters, W. E.Development of an ethical committee and its effect on research design. Lancet, 1982, i, 1233–36.CrossRefGoogle Scholar
2.Angell, M.Patients’ preferences in randomized clinical trials [editorial]. New England Journal of Medicine, 1984, 310, 1385–87.CrossRefGoogle ScholarPubMed
3.Baines, C. J.Impediments to recruitment in the Canadian National Breast Cancer Study: Response and resolution. Controlled Clinical Trial, 1984, 5, 129–40.CrossRefGoogle ScholarPubMed
4.Baker, M. T., & Taub, H. A.Readibility of informed consent forms for research in a Veterans Administration Medical Center. Journal of the American Medical Association, 1983, 250, 2646–48.CrossRefGoogle Scholar
5.Barnett, H. J. M., Sackett, D., Taylor, D. W., et al. Are the results of the Extracranial Intracranial Bypass Trial generalizable? New England Journal of Medicine, 1987, 316, 820–24.CrossRefGoogle ScholarPubMed
6.Barofsky, I., & Sugarbaker, P. H.Determinants of patient non-participation in randomized clinical trials for the treatment of sarcoma. Cancer Clinical Trials, 1979, 2, 237–46.Google Scholar
7.Brensike, J. F., Kelsey, S. F., Passamani, E. R., et al. National Heart, Lung and Blood Institute Type II Coronary Intervention Study: Design, methods and baseline characteristics. Controlled Clinical Trials, 1982, 3, 91–111.CrossRefGoogle ScholarPubMed
8.Buchwald, H. B., Fitch, L. L., Matts, J. P., et al. for the POSCH group. Perception of quality of life before and after disclosure of trial results: A report from the program on the surgical control of the hyperlipidemias (POSCH). Controlled Clinical Trials, 1993, 14, 500–10.CrossRefGoogle ScholarPubMed
9.Caschetta, M., Chavkis, W., & McGovern, T.FDA policy on women in drug trials [letter]. New England Journal of Medicine, 1993, 329, 1815.Google ScholarPubMed
10.Chalmers, I.Under-reporting research is scientific misconduct. Journal of the American Medical Association, 1990, 263, 1405–08.CrossRefGoogle Scholar
11.Charlson, M. E., & Horwitz, R. I.Applying results of randomized trials to clinical practice: Impact of losses before randomization. British Medical Journal, 1984, 289, 1281–84.CrossRefGoogle Scholar
12.Collins, J. F., Bingham, S. F., Williford, W. O., & Weiss, D. G.Who drops out of clinical trials? The VA Cooperative Study experience [Abstract]. Controlled Clinical Trials, 1981, 2, 78.CrossRefGoogle Scholar
13.Collins, R., Doll, R., & Peto, R. Ethics of clinical trials. In Williams, C. J. (ed.), Introducing new treatments for cancer: Practical, ethical and legal problems. Chichester: John Wiley, 1992, 49–65.Google Scholar
14.Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization. Informed consent of subjects. In International guidelines for biomedical research involving human subjects. Geneva: WHO, 1993, 13–17.Google Scholar
15.Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization. Pregnant or nursing women as research subjects. In International guidelines for biomedical research involving human subjects. Geneva: WHO, 1993, 33–34.Google Scholar
16.Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization. Research involving children. In International guidelines for biomedical research involving human subjects. Geneva: WHO, 1993, 20–21.Google Scholar
17.Dahan, R., Caulin, C., Figea, L., et al. Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital. British Medical Journal, 1986, 293, 363–64.CrossRefGoogle ScholarPubMed
18.Deber, R. B., & Thompson, G. G.Variations in breast cancer treatment decisions and their impact in mounting trials. Controlled Clinical Trials, 1990, 13, 353–73.CrossRefGoogle Scholar
19.Dickersin, K., Chan, S., Chalmers, T. C., et al. Publication bias and clinical trials. Controlled Clinical Trials, 1987, 8, 343–53.CrossRefGoogle ScholarPubMed
20.Editorial. Consent: How informed? Lancet, 1984, i, 1445–47.Google Scholar
21.Editorial. On stopping a trial before its time. Lancet, 1993, 342, 1311–12.CrossRefGoogle Scholar
22.Editorial. Volunteering for research. Lancet, 1992, 340, 823–24.CrossRefGoogle Scholar
23.Edlund, M. J., Craig, T. J., & Richardson, M. A.Informed consent as a form of volunteer bias. American Journal of Psychiatry, 1985, 142, 624–27.Google ScholarPubMed
24.Ellenberg, S., Geller, N., Simon, R., & Yusuf, S. (eds). Practical issues in data monitoring of clinical trials. Statistics in Medicine, 1993, 12, 415–616.CrossRefGoogle Scholar
25.Ellenberg, S. S., Cooper, E., Eigo, J., et al. Studying treatments for AIDS: New challenges for clinical trials. A panel discussion at the 1990 Annual Meeting of the Society for Clinical Trials. Controlled Clinical Trials, 1992, 13, 272–92.CrossRefGoogle Scholar
26.Fletcher, A., Spiegelhalter, D., Staenssen, J., et al. Implications for trials in progress of publication of positive results. Lancet, 1993, 342, 653–57.CrossRefGoogle ScholarPubMed
27.French, K., Porter, A. M. D., Robinson, S. E., et al. Attendance at a breast screening clinic: A problem of administration or attitudes? British Medical Journal, 1982, 285, 617–20.CrossRefGoogle ScholarPubMed
28.Goldman, J., & Katz, M. D.Inconsistency and institutional review boards. Journal of the American Medical Association, 1982, 248, 197–202.CrossRefGoogle ScholarPubMed
29.Goldman, J. F., Holcomb, R., Perry, H. M., et al. Can dropout and other noncompliance be minimized in a clinical trial? Report from Veterans Administrative National Heart, Lung and Blood Institute Cooperative Study on Antihypertensive Therapy: Mild hypertension. Controlled Clinical Trials, 1982, 3, 75–89.CrossRefGoogle Scholar
30.Grady, D., Rubin, S., Petitti, D., et al. Hormone therapy to prevent disease and prolong life in post-menopausal women. Annals of Internal Medicine, 1992, 117, 1016–37.CrossRefGoogle Scholar
31.Green, S. B., Ellenberg, S. S., Finklestein, D., Issues in the design of drug trials for AIDS. Controlled Clinical Trials, 1990, 11, 80–87.CrossRefGoogle ScholarPubMed
32.Greenlick, M. R., Bailey, J. W., Wild, J., & Grover, J.Characteristics of men most likely to respond to an invitation to be screened. American Journal of Public Health, 1979, 69, 1011–13.CrossRefGoogle Scholar
33.Haynes, R. B., & Dantes, R.Patient compliance and the conduct and interpretation of therapeutic trials. Controlled Clinical Trials, 1987, 8, 12–19.CrossRefGoogle ScholarPubMed
34.Herxheimer, A.The rights of the patient in clinical research. Lancet, 1988, ii, 1128–30.CrossRefGoogle Scholar
35.Hughes, J. R.Exclusion of ‘non-compliant’ individuals from clinical trials [letter]. Controlled Clinical Trials, 1993, 13, 176–77.CrossRefGoogle Scholar
36.Hunninghake, D. B.Summary conclusions. Controlled Clinical Trials, 1987, 8(suppl. 4), 1S–5S.CrossRefGoogle Scholar
37.Hunninghake, D. B., Darby, C. A., & Probstfield, J. L.Recruitment experience in clinical trials: Literature summary and annotated bibliography. Controlled Clinical Trials, 1987, 8(suppl. 4), 6S–30S.CrossRefGoogle ScholarPubMed
38.Hunter, C., Frelick, R. W., Feldman, A. R., et al. Selection factors in clinical trials: Results from the Community Clinical Oncology Program Physician’s patient log. Cancer Treatment Reports, 1987, 71, 559–65.Google ScholarPubMed
39.Hypertension Detection and Follow-up Program Cooperative Group. Patient participation in a hypertension control program. Journal of the American Medical Association, 1978, 239, 1507–15.Google Scholar
40.Katz, J.Randomised clinical trials. ‘Am I my brother’s keeper?.’ Journal of Clinical Gastroenterology, 1981, 3(suppl.), 141–46.Google Scholar
41.Kerrigan, D. D., Thevasagayam, R. S., Woods, T. O., et al. Who‘s afraid of informed consent? British Medical Journal, 1993, 306, 298–300.CrossRefGoogle ScholarPubMed
42.King, J.Informed consent: A review of the empirical evidence. Institute of Medical Ethics Bulletin, 1986, 3(suppl.), 1–19.Google Scholar
43.Klawanski, S., Berkey, C., Shah, N., et al. Survival from localized breast cancer: Variability across trials and registries. International Journal of Technology Assessment in Health Care, 1993, 9, 539–53.CrossRefGoogle Scholar
44.Koren, G.Ethical boundaries of medical research in infants and children in the 80s: Analysis of rejected protocols and a new solution for drug studies. Developments in Pharmacology and Therapeutics, 1990, 15, 130–41.CrossRefGoogle Scholar
45.Koren, G., Birenbaum, D.,Carmeli, Y. S., & Haslam, R.Maturity of children to consent to medical research: The babysitter test. Journal of Medical Ethics, 1993, 19, 142–47.CrossRefGoogle ScholarPubMed
46.Lasagna, L.Problems in publication of clinical trial methodology. Clinical Pharmacology and Therapeutics, 1979, 25, 751–53.CrossRefGoogle ScholarPubMed
47.Lau, J., Antman, E. M., Jimenez-Silva, J., et al. Cumulative meta-analyses of therapeutic trials for myocardial infarction. New England Journal of Medicine, 1992, 327, 248–54.CrossRefGoogle ScholarPubMed
48.Launer, J.Informed consent. British Medical Journal, 1986, 293, 627–28.CrossRefGoogle Scholar
49.Laupacis, A., Connolly, S. J., Gent, M., et al. How should results from completed studies influence ongoing trials? Annals of Internal Medicine, 1991, 115, 818–22.CrossRefGoogle Scholar
50.Lee, J. Y., & Breaux, S. R.Accrual of radiotherapy patients to clinical trials. Cancer, 1983, 52, 1014–16.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
51.Lee, J. Y., Marks, J. E., & Simpson, J. R.Age as a criterion for eligibility in a lung cancer trial. Cancer Clinical Trials, 1982, 5, 449–53.Google Scholar
52.Levenkron, J. C., & Farquhar, J. W.Recruitment using mass media strategies. Circulation, 1982, 66(suppl.), IV–32–IV–36.Google ScholarPubMed
53.Lumley, J., Lester, A., Renou, P., & Wood, C.A failed RCT to determine the best method of delivery for very low birth weight infants. Controlled Clinical Trials, 1985, 6, 120–27.CrossRefGoogle ScholarPubMed
54.Lurie, P., Bishaw, M., Chesney, M. A., et al. Ethical, behavioral and social aspects of HIV vaccine trials in developing countries. Journal of the American Medical Association, 1994, 271, 295–301.CrossRefGoogle ScholarPubMed
55.Lynoe, N., Sandlund, M., Dahlqvist, G., & Jacobbson, L.Informed consent: Study of quality of information given to participants in a clinical trial. British Medical Journal, 1991, 303, 610–613.CrossRefGoogle ScholarPubMed
56.Macara, A. W.Ethical review of multi-centred trials. Journal of Medical Ethics, 1990, 16, 150–52.CrossRefGoogle ScholarPubMed
57.Marshall, G. D.Overview of recruitment to the coronary primary prevention trial. Circulation, 1982, 66(suppl.), IV-5–IV–9.Google Scholar
58.Marteau, T. M., Kidd, J., Michie, S., et al. Anxiety, knowledge and satisfaction in women receiving false positive results on routine prenatal screening: A randomized controlled trial. Journal of Psychosomatic Obstetrics and Gynaecology, 1993, 14, 185–86.CrossRefGoogle ScholarPubMed
59.Martin, J. E., Henderson, W. G., Zacharski, L. R., et al. Accrual of patients into a multihospital cancer trial and its implications on planning future studies. American Journal of Clinical Oncology, 1984, 7, 173–82.CrossRefGoogle ScholarPubMed
60.Mastroianno, A. C., Faden, R., & Federman, D. (eds.). Women and health research: Ethical and legal issues of including women in clinical studies. Washington, DC: Institute of Medicine, 1994.Google Scholar
61.McCusker, E. A., Wax, A., & Bennett, J. M.Cancer patient accessions into clinical trials: A pilot investigation into some patient and physician determinants of entry. American Journal of Clinical Oncology, 1982, 5, 227–36.CrossRefGoogle ScholarPubMed
62.McNeill, P.The ethics and politics of human experimentation. Cambridge: Cambridge University Press, 1993, 159.Google Scholar
63.McNeill, P. Giving effect to representation: Composition and functioning of review committees. The ethics and politics of human experimentation. Cambridge: Cambridge University Press, 1993, 207–36.Google Scholar
64.Meisel, A., & Roth, L. H.What we do and do not know about informed consent. Journal of the American Medical Association, 1981, 246, 2473–77.CrossRefGoogle Scholar
65.Mike, V., Kraus, A. N., & Ross, G. S.Neonatal extracorporeal membrane oxygenation (ECMO): Clinical trials and the ethics of evidence. Journal of Medical Ethics, 1993, 19, 212–18.CrossRefGoogle ScholarPubMed
66.Moore, R. D., Stanton, D., Gopalan, R., & Chaisson, R.Racial differences in the use of drug therapy for HIV disease in an urban community. New England Journal of Medicine, 1994, 330, 763–68.CrossRefGoogle Scholar
67.MRC Vitamin Study Research Group. Prevention of neural tube defects: Result of the Medical Research Council vitamin study. Lancet, 1991, 338, 131–37.CrossRefGoogle Scholar
68.Myers, M. G., Cairns, J. A., & Singer, J.The consent form as a possible cause of side-effects. Bioethics News, 1993, 12, 4–9.Google Scholar
69.Mynaugh, P. A.A randomized study of two methods of teaching perineal massage: Effects on practice rates, episiotomy rates and lacerations. Birth, 1991, 18, 153–58.CrossRefGoogle ScholarPubMed
70.National Health and Medical Research Council, Commonwealth of Australia. Guidelines on ethical matters in Aboriginal and Torres Strait islander health research. Proceedings of the 111th Session, 1991.Google Scholar
71.Naylor, C. D., Chen, E., & Strauss, B.Measured enthusiasm: Does the method of reporting trial results alter perceptions of therapeutic effectiveness? Annals of Internal Medicine, 1992, 117, 916–21.CrossRefGoogle ScholarPubMed
72.NIH/ADAMHA policy concerning inclusion of minorities in study populations. NIH guide for grants and contracts 20 (No. 32). 08 23.1, 1991.Google Scholar
73.NIH/ADAMHA policy concerning inclusion of women in study populations. NIH guide for grants and contracts 20 (No. 32). 08 23:1, 1991.Google Scholar
74.Orr, P. R., Blackhurst, D. W., Hawkins, B. S., for the Macular Photocoagulation Study Group. Patient and clinic factors predictive of missed visits and inactive status in a multicenter clinical trial. Controlled Clinical Trials, 1992, 13, 40–49.CrossRefGoogle Scholar
75.Oxman, A. D., & Guyatt, G. H.A consumer’s guide to subgroup analysis. Annals of Internal Medicine, 1992, 116, 78–84.CrossRefGoogle Scholar
76.Pettit, P.Instituting a research ethic: Chilling and cautionary tales. Bioethics News, 1992, 11(suppl. 4), 3–21.Google Scholar
77.Piantadosi, S., & Wittes, J.Politically correct trials [letter]. Controlled Clinical Trials, 1993, 14, 562–67.CrossRefGoogle Scholar
78.Rubins, H. B.From clinical trials to clinical practice: Generalising from participant to patient. Controlled Clinical Trials, 1994, 15, 7–10.CrossRefGoogle ScholarPubMed
79.Rudick, C., Anthonisen, N. R., & Manfreda, J.Recruiting healthy participants for a large clinical trial. Controlled Clinical Trials, 1993, 14(suppl. 2), 68S–79S.CrossRefGoogle ScholarPubMed
80.Silverman, W. A.Human experimentation. A guided step into the unknown. Oxford; OUP, 1985.Google Scholar
81.Simberkoff, M. S., Hartigan, P. M., Hamilton, J. D., et al. Ethical dilemmas in continuing a zidovudine trial after early termination of similar trials. Controlled Clinical Trials, 1993, 14, 6–18.CrossRefGoogle ScholarPubMed
82.Simel, D. L., & Feussner, J. R.A randomized controlled trial comparing quantitative informed consent formats. Journal of Clinical Epidemiology, 1991, 44, 771–77.CrossRefGoogle ScholarPubMed
83.Simes, R. J., Tattersall, M. H. N., Coates, A. S., et al. Randomised comparisons of procedures for obtaining informed consent in clinical trials of treatment for cancer. British Medical Journal, 1986. 293, 1065–68.CrossRefGoogle ScholarPubMed
84.Simpson, M., Buckman, R., Stewart, M., et al. Doctor-patient communication: The Toronto consensus statement. British Medical Journal, 1991, 303, 1385–87.CrossRefGoogle ScholarPubMed
85.Smithells, R. W., & Sheppard, S.Possible prevention of neural-tube defects by periconceptional vitamin supplements [letter]. Lancet, 1980, i, 647.CrossRefGoogle Scholar
86.Society for Clinical Trials. Recommendations to the director of NIH from the membership of the Society for Clinical Trials. Controlled Clinical Trials, 1993, 14, 559.CrossRefGoogle Scholar
87.Souhami, R. L., & Whitehead, J. (eds). Workshop on early stopping rules in cancer clinical trials. Statistics in Medicine, 1994, 13, 1293–95.CrossRefGoogle Scholar
88.Stewart, D. E., Lickrish, G. M., Sierra, S., & Parkin, H.The effect of educational brochures on knowledge and emotional distress in women with abnormal Papanicolaou smears. Obstetrics and Gynecology, 1993, 81, 280–82.Google ScholarPubMed
89.Tarnowski, K. J., Allen, D. M., Mayhall, C., & Kelly, P. A.Readability of pediatric biomedical research forms. Pediatrics, 1990, 85, 58–62.CrossRefGoogle Scholar
90.Taylor, K. M., Margolese, R. G., & Soskolne, C. L.Physicians’ reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer. New England Journal of Medicine, 1984, 310, 1363–67.CrossRefGoogle ScholarPubMed
91.Taylor, K. M., Shapiro, M., Soskolne, C. L., & Margolese, R. G.Physician response to informed consent regulations for randomized clinical trials. Cancer, 1987, 60, 1415–22.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
92.Thomas, E.Informed consent [letter]. Lancet, 1986, ii, 1280.CrossRefGoogle Scholar
93.Thong, Y. H., & Harth, S. C.The social filter effect of informed consent in clinical research. Pediatrics, 1991, 87, 568–69.CrossRefGoogle ScholarPubMed
94.Tobias, J. S. Informed consent and the introduction of new cancer treatments. In Williams, C. J. (ed.), Introducing new treatments for cancer: Practical, ethical and legal problems. Chichester: John Wiley, 1992, 67–77.Google Scholar
95.Tuckett, D., & Williams, A.Approaches to the measurement of explanation and information-giving in medical consultations: A review of empirical studies. Social Science and Medicine, 1984, 18, 571–80.CrossRefGoogle Scholar
96.Vollmer, W. M., Hertert, S., & Allison, M. J.Recruiting children and their families for clinical trials: A case study. Controlled Clinical Trials, 1992, 13, 315–20.CrossRefGoogle ScholarPubMed
97.Waldenstron, U., & Gotvall, K.A randomised trial of birthing stool or conventional semirecumbent position for second stage labor. Birth, 1991, 18, 5–10.CrossRefGoogle Scholar
98.Walterspiel, J. N.Informed consent: Influence on patient selection among critically ill premature infants. Pediatrics, 1990, 85, 119–21.CrossRefGoogle ScholarPubMed
99.Wilhelmson, L., Ljundberg, S., Wedel, H., & Werko, L.A comparison between participants and non-participants in a primary prevention trial. Journal of Chronic Diseases, 1976, 29, 331–39.CrossRefGoogle Scholar
100.Wittes, J.Behind closed doors: The data monitoring board in randomized clinical trials. Statistics in Medicine, 1993, 12, 419–24CrossRefGoogle ScholarPubMed
101.Wittes, J.Introduction: From clinical trials to clinical practice: Four papers from a plenary session. Controlled Clinical Trials, 1994, 15, 5–6.CrossRefGoogle Scholar
102.Yusuf, S., Held, P., Teo, K. K., & Toretsky, E. R.Selection of patients for randomised controlled trials: Implications of wide or narrow eligibility criteria. Statistics in Medicine, 1990, 9, 73–86.CrossRefGoogle ScholarPubMed
103.Zelen, M.A new design for randomized clinical trials. New England Journal of Medicine, 1979, 317, 141–45.Google Scholar