Articulating and Responding to Uncertainties in Clinical Research 

Author: Benjamin Djulbegovic ^a

Affiliation:

a University of South Florida, Tampa, Florida, USA

DOI: 10.1080/03605310701255719

Publication Frequency: 6 issues per year

Published in: Journal of Medicine and Philosophy, Volume 32, Issue 2 March 2007 , pages 79 - 98

Subjects: Medicine: Medical Ethics; Ethics Philosophy: Medical Ethics;

Formats available: HTML (English) : PDF (English)

You have: FREE ACCESS

The circumstances under which this title is published have changed:

Reason for change: Changed Publisher
Now published by: Oxford University Press
Date of change: 2008

References

• 1. Arrow, K. (1963) Social Choice and Individual Values 2nd, Wiley and Yale University Press , New York
• 2. Ashcroft, R. (1999) Equipoise, knowledge and ethics in clinical research and practice. Bioethics 13 , pp. 314-326. [ pubmed ] [ csa ]
• 3. Chalmers, I. Egger, M.,  Smith, G. D. and Altman, D. G. (eds) (2001) Using systematic reviews and registers of ongoing trials for scientific and ethical trial design, monitoring, and reporting. Systematic Reviews in Health Care: Meta-Analysis in Context pp. 429-443. London — British Medical Journal
• 4. Chalmers, I. (2004) Well informed uncertainties about the effects of treatments. British Medical Journal 328:7438 , pp. 475-476. [ crossref ] [ pubmed ]
• 5. Chalmers, I.,  Grant, J.,  Cottrell, R.,  Cluzeau, F. and Fawcett, G. (2000) Evaluating “payback” on biomedical research: Biomedical funding decisions should be audited. British Medical Journal 321 , p. 566. [ crossref ] [ pubmed ]
• 6. Chalmers, I. and Matthews, R. (2006) What are implications of optimism bias in clinical research?. Lancet 367 , pp. 449-450. [ crossref ] [ pubmed ]
• 7. Collins, R. and McMahon, S. (2001) Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials. Lancet 357 , pp. 373-380. [ crossref ] [ csa ] [ pubmed ]
• 8. Courtney, H.,  Kirkland, J. and Viguerie, P. (1999) Strategy under uncertainty. Harvard Business Review 75 , pp. 66-79. — 1999 [ csa ]
• 9. Daniel, N. and Sabin, J. (1997) Limits to health care: Fair procedures, democratic deliberations, and the legitimacy problem for insurers. Philosophy and Public Affairs 26 , pp. 303-350. [ crossref ] [ csa ]
• 10. Dixit, A. and Skeath, S. (2004) Games of Strategy 2nd, W.W. Norton , New York
• 11. http://www.hsc.usf.edu/∼bdjulbeg/oncology/NON-RCT-practice-change.htm — Djulbegovic, B. (2000, June 12). Non-randomized trials that changed medical practice [On-line]
• 12. Djulbegovic, B. (2001) Acknowledgment of uncertainty: A fundamental means to ensure scientific and ethical validity in clinical research. Current Oncology Reports 3 , pp. 389-395. [ csa ] [ pubmed ]
• 13. Djulbegovic, B. Perry, M. (ed) (2003) Principles of research synthesis. ASCO Annual Meeting, (Educational Session) ASCO pp. 737-750. ASCO , Washington, DC
• 14. Djulbegovic, B. (2004) Well informed uncertainties about the effects of treatment: Paradox exists in dealing with uncertainty. British Medical Journal 328:7446 , p. 1018. [ crossref ] [ pubmed ]
• 15. Djulbegovic, B. and Bercu, B. (March 2002) At what level of collective equipoise does a clinical trial become ethical for the IRB members?. USF Third National Symposium—Bioethical Considerations in Human Subject Research Clearwater, Florida
• 16. Djulbegovic, B.,  Cantor, A. and Clarke, M. (2003) The importance of the preservation of the ethical principle of equipoise in the design of clinical trials: Relative impact of the methodological quality domains on the treatment effect in randomized controlled trials. Accountability in Research 10 , pp. 301-315. [informaworld]
• 17. Djulbegovic, B. and Hozo, I. (2002) At what degree of belief in a research hypothesis is a trial in humans justified?. Journal of Evaluation in Clinical Practice 8 , pp. 269-276. [ crossref ] [ csa ] [ pubmed ]
• 18. Foster, C. (2001) The Ethics of Medical Research on Humans Cambridge University Press , Cambridge
• 19. Freedman, B. (1987) Equipoise and the ethics of clinical research. New England Journal of Medicine 317 , pp. 141-145.
• 20. Fried, C. (ed) (1974) Medical Experimentation: Personal Integrity and Social Policy North Holland , Amsterdam
• 21. Good, I. J. (1967) On the principle of total evidence. British Journal for the Philosophy of Science 17 , pp. 319-321. [ crossref ]
• 22. GRADE Working Group (2004) Grading quality of evidence and strength of recommendations. British Medical Journal 328:7454 , p. 1490. [ crossref ] [ pubmed ]
• 23. Hastie, R. and Dawes, R. M. (2001) Rational Choice in an Uncertain World Sage Publications, Inc , London
• 24. Hill, A. B. (1952) The clinical trial. New England Journal of Medicine 247 , pp. 113-119.
• 25. Hill, A. B. (1963) Medical ethics and controlled trials. British Medical Journal 2 , pp. 1043-1049. [ pubmed ]
• 26. Hill, A. B. (1987) Clinical trials and the acceptance of uncertainty. British Medical Journal 294 , p. 1419.
• 27. Joffe, S.,  Harrington, D. P.,  George, S.,  Emanuel, E.,  Budzinski, L. and Weeks, J. (2004) Satisfaction of the uncertainty principle in cancer clinical trials: Retrospective cohort analysis. British Medical Journal 328:7454 , pp. 1463-1467. [ crossref ] [ pubmed ]
• 28. Joffe, S.,  Stumacher, M.,  Clark, J. and Weeks, J. (2006) Preferences for and expectations about experimental therapy among participants in randomized trials. Journal of Clinical Oncology 24:18s , p. 304s.
• 29. Johnson, N.,  Lilford, J. R. and Brazier, W. (1991) At what level of collective equipoise does a clinical trial become ethical?. Journal of Medical Ethics 17 , pp. 30-34. [ pubmed ]
• 30. Kant, I. (1964) Groundwork of the Metaphysics of Morals Harper Torchbook , New York — H.J. Paton (Trans.)
• 31. Kumar, A.,  Soares, H. P. and Djulbegovie, B. (2005a) High proportion of high quality trials conducted by the NCI are negative or inconclusive. XIII Cochrane Colloquium Melbourne, Australia
• 32. Kumar, A.,  Soares, H. P.,  Wells, R.,  Clarke, M.,  Hozo, I.,  Bleyer, A.,  Reaman, G.,  Chalmers, I. and Djulbegovic, B. (2005b) What is the probability that a new treatment for cancer in children will be superior to an established treatment? An observational study of randomised controlled trials conducted by the Children's Oncology Group. British Medical Journal 331 , pp. 1295-1301. [ crossref ] [ pubmed ]
• 33. Lilford, R. J. and Djulbegovic, B. (2001) Equipoise and “the uncertainty principle” are not mutually exclusive. British Medical Journal 322 , p. 795. [ crossref ] [ pubmed ]
• 34. Lilford, R. J. and Jackson, J. (1995) Equipoise and the ethics of randomization. Journal of the Royal Society of Medicine 88 , pp. 552-559. [ pubmed ]
• 35. Mann, H. and Djulbegovic, B. (2003) Choosing a control intervention for a randomized clinical trial. BMC Medical Research Methodology 3 , p. 7. [ crossref ] [ pubmed ]
• 36. www.jameslindlibrary.org/essays/bias/comparator-bias.html — Mann, H. & Djulbegovic, B. (2004, August 20). Why comparisons must address genuine uncertainties [On-line]
• 37. Miller, F. G. and Rosenstein, D. L. (2003) The therapeutic orientation to clinical trials. New England Journal of Medicine 348:14 , pp. 1383-1386. [ crossref ]
• 38. Mills, N.,  Donovan, J. L.,  Smith, M.,  Jacoby, A.,  Neal, D. E. and Hamdy, F. C. (2003) Perceptions of equipoise are crucial to trial participation: A qualitative study of men in the ProtecT study. Controlled Clinical Trials 24 , pp. 272-282. [ crossref ] [ csa ] [ pubmed ]
• 39. Moher, D.,  Schultz, K. F. and Altman, D. (2001) For the CONSORT group. The CONSORT statement: Revised recommendations for improving the quality of reports of parallel-group randomized trials. Journal of the American Medical Association 285 , pp. 1987-1991. [ crossref ] [ pubmed ]
• 40. Peto, R. and Baigent, C. (1998) Trials: The next 50 years. British Medical Journal 317 , pp. 1170-1171. [ pubmed ]
• 41. Rawls, J. (1999) A Theory of Justice Harvard University Press , Revised edition). Cambridge, MA
• 42. Shannon, C. E. and Waever, W. (1962) The Mathematical Theory of Communication The University of Illinois Press , Urbana
• 43. Silverman, W. A. and Chalmers, I. (2001) Casting and drawing lots: A time-honoured way of dealing with uncertainty and for ensuring fairness. British Medical Journal 323 , pp. 1467-1468. [ pubmed ] [ crossref ]
• 44. Soares, H. P.,  Kumar, A.,  Daniels, S.,  Swann, S.,  Cantor, A.,  Hozo, I.,  Clark, M.,  Serdarevic, F.,  Gwede, C.,  Trotti, A. and Djulbegovic, B. (2005) Evaluation of new treatments in radiation oncology: Are they better than standard treatments?. Journal of the American Medical Association 293:8 , pp. 970-978. [ pubmed ] [ crossref ]
• 45. Veatch, R. M. (2002) Indifference of subjects: An alternative to equipoise in randomized clinical trials. Social Philosophy & Policy 19 , pp. 295-323. [ crossref ]
• 46. Warlow, C. (2002) Advanced issues in the design and conduct of randomized clinical trials: The bigger the better?. Stat Med 21 , pp. 2797-2805. [ crossref ]
• 47. Weijer, C.,  Shapiro, S. H. and Cranley, K. (2000) Clinical equipoise and not the uncertainty principle is the moral underpinning of the randomized trial. For and against. British Medical Journal 321 , pp. 756-758. [ pubmed ] [ crossref ]
• 48. Welch, H. G. and Mogielnicki, J. (2002) Presumed benefit: Lessons from the American experience with marrow transplantation for breast cancer. British Medical Journal 324:7345 , pp. 1088-1092. [ pubmed ] [ crossref ]
• 49. Wittgenstein, L. (1969) On Certainty Harper Torchbooks , New York
• 50. World Medical Association (2000) World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Journal of the American Medical Association 284 , pp. 3043-3045. [ pubmed ] [ crossref ]