Which benefits of research participation count as 'direct'?

Bioethics

Volumn 26, Issue 2, 2012, Pages 60-67

  Friedman, Alexander ^a   Robbins, Emily ^b   Wendler, David ^c  

^a NIH Department of Bioethics   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Direct benefits; Fallacy of the package deal; Informed consent; Vulnerable subjects

Indexed keywords

ARTICLE; BENEFICENCE; ETHICS; HUMAN; INFORMED CONSENT; MEDICAL RESEARCH; RESEARCH SUBJECT;

BENEFICENCE; BIOMEDICAL RESEARCH; HUMANS; INFORMED CONSENT; RESEARCH SUBJECTS;

EID: 84856055963     PISSN: 02699702     EISSN: 14678519     Source Type: Journal    
DOI: 10.1111/j.1467-8519.2010.01825.x     Document Type: Article

References (32)

1. Council for International Organizations of Medical Sciences. 2002. International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva, Switzerland: guideline 9. Available at: http://www.cioms.ch/frame_guidelines_nov_2002.htm [Accessed: 5 April 2010].
2. International Conference on Harmonization. 1996. Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance. Guidelines 4.8.13 and 4.8.14. Available at: http://www.ema.europa.eu/pdfs/human/ich/013595en.pdf [Accessed: 5 April 2010].
3. Department of Health and Human Services. Code of Federal Regulations. Title 45, Part 46, Protection of Human Subjects, subpart D; Food and Drug Administration. Code of Federal Regulations. Title 21, Part 50. Protection of Human Subjects, subpart D. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm [Accessed: 5 April 2010].
4. The Commission held that the most problematic research with those who cannot consent is 'research that presents more than minimal risk without immediate prospect of direct benefit'. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1979. The Belmont Report. Available at: http://ohsr.od.nih.gov/guidelines/belmont.html [Accessed: 5 April 2010].
5. Report regarding the ethics of research involving people institutionalized as mentally infirm. Federal Register 1978: 11334. Available at: http://www.hhs.gov/ohrp/documents/19780317.pdf [Accessed: 5 April 2010].
6. E Keyserlingk, K. Glass, S. Kogan & S. Gauthier. Proposed Guidelines for the Participation of Persons with Dementia as Research Subjects. Perspect Biol Med 1995; 38: 319-361.
7. Institute of Medicine. 2004. Ethical Conduct of Clinical Research Involving Children. Washington, DC: National Academies Press: 132.
8. World Medical Association. 59th General Assembly, Seoul, October 2008, Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, principle 27. Available at: http://www.wma.net/e/policy/b3.htm [Accessed: 15 July 2009].
9. Tri-Council Policy Statement. Ethical Conduct for Research Involving Humans. 2005. Article 2.5(c). Available at: http://www.pre.ethics.gc.ca/eng/policy-politique/tcps-eptc/ [Accessed: 5 April 2010].
10. For purposes of evaluating the concept of direct benefits, we will bracket the possibility that there might be appropriate exceptions to this requirement. For example, it might be appropriate, in some instances,to allow adults who cannot consent to be enrolled in riskier research when there is compelling evidence that such participation is consistent with the individuals' competent preferences and values.
11. C. Grady. Payment of Clinical Research Subjects. J Clin Invest 2005; 115: 1681-1687; T. Chambers. Participation as Commodity, Participation as Gift. Am J Bioeth 2001; 1: 48.
12. T. Chambers. Participation as Commodity, Participation as Gift. Am J Bioeth 2001; 1: 48.
13. This objection faces the significant problem that a good deal of research is funded by private companies whose goal is ultimately to make a profit.
14. Grimes v. Kennedy Krieger Institute, Inc., 782 A.2d 807 (Md. Ct. of App. 2001, reconsideration denied, Oct. 11, 2001). See pages 9 and 61, especially footnote 34. Some of the court's concern seems to trace to the potential for such offers to undermine the validity of parental permission and subject assent. The court also suggests that such offers are per se inappropriate in the context of clinical research.
15. NIH Office of Human Subjects Research. Guidelines for Remuneration of Research Subjects. Available at: http://ohsr.od.nih.gov/info/sheet20.html [Accessed 13 September 2009].
16. National Council for Science and Technology. 2004. Guidelines for Ethical Conduct of Biomedical Research Involving Human Subjects in Kenya. Nairobi: National Council for Science and Technology: 6.
17. Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity. 1998. Volume I: Report and Recommendations of the National Bioethics Advisory Commission: 45. Available at: http://bioethics.georgetown.edu/nbac/capacity/TOC.htm [Accessed: 5 April 2010].
18. N. King. Defining and Describing Benefit Appropriately in Clinical Trials. J Law Med Ethics 2000; 28: 332-343.
19. There are exceptions, of course. A single administration as part of an early phase trial may well offer no potential for clinical benefit.
20. To be clear, this claim is not intended to cover clinical care interventions that are sometimes included in clinical research studies. Rather, the point is that research studies sometimes include interventions that are not part of clinical care, but nonetheless offer some potential for clinical benefit.
21. C. Weijer. The Ethical Analysis of Risk in Intensive Care Unit Research. Crit Care 2004; 8: 85-86; A. McRae & C. Weijer. U.S. Federal Regulations for Emergency Research: a Practical Guide and Commentary. Acad Emerg Med 2008; 15: 88-97.
22. A. McRae & C. Weijer. U.S. Federal Regulations for Emergency Research: a Practical Guide and Commentary. Acad Emerg Med 2008; 15: 88-97.
23. See, for example, the US National Commission. 1977. Report and recommendations: research involving children. Washington, DC: U.S. Government Printing Office: 6-7.
24. Institute of Medicine. 2004. Ethical conduct of clinical research involving children. M.J. Field & R.E. Behrman, eds. Washington, DC: National Academies Press: 138.
25. R.J. Levine. The Need to Revise the Declaration of Helsinki. New Engl J Med 1999; 341: 531-534.
26. National Bioethics Advisory Commission. 2001. Ethical and policy issues in research involving human participants. Bethesda, MD: Report and recommendations of the National Bioethics Advisory Commission: ch. 4, p. 78.
27. Specially, the International Conference on Harmonization specifies that non-therapeutic trials (i.e. a trial in which there is no anticipated direct clinical benefit to the subject) may be conducted in subjects with consent of a legally acceptable representative provided the following conditions are fulfilled: (a) The objectives of the trial can not be met by means of a trial in subjects who can give informed consent personally; (b) The foreseeable risks to the subjects are low; (c) The negative impact on the subject's well-being is minimized and low.
28. The objectives of the trial can not be met by means of a trial in subjects who can give informed consent personally
29. The foreseeable risks to the subjects are low
30. The negative impact on the subject's well-being is minimized and low.
31. Specifically, subpart D of the US regulations state that 'HHS will conduct or fund research in which the IRB finds that more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject' when the IRB finds that 'the risk is justified by the anticipated benefit to the subjects'. Department of Health and Human Services. Code of Federal Regulations. Title 45, Part 46, Protection of Human Subjects, 45CFR46.405. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm [Accessed: 5 April 2010].
32. We are assuming here that the intentions of the investigators who perform the biopsies roughly track the potential that the biopsies will benefit the subjects.