Current regulations and guidelines identify specific subject populations as vulnerable. Regulations and guidelines generally stipulate protections with regard to the process of informed consent. Recent clinical trials suggest that satisfying the legal requirements for additional safeguards may not protect subjects to the extent we may desire. We present proposed guidelines for the protection of decisionally impaired subjects throughout the course of the trial.
BeecherHK. Ethics and clinical research. N Engl J Med1966; 274: 1354–1360.
2.
JonesJ. Bad Blood: The Tuskegee Syphilis Experiments, 2nd ed. New York, NY: Free Press, 1993.
3.
MorenoJD. Undue Risk: Secret State Experiments on Humans, New York, NY: Routledge, 2001.
4.
RothmanDJRothmanSM. The Willowbrook War, Piscataway, NJ: Transaction Publishers, 2005.
5.
KatzJ. Experimentation with Human Beings, New York, NY: Russell Sage Foundation, 1972.
6.
CFR 46.111(b).
7.
Stephen C. Olson, M.D. FDA Establishment Inspection Report Weiss v. UM et al. Fourth Dist. Ct. Hennepin County, MN 27-CV-07-1679 [Exhibit J] 2005-07-22, http://www.circare.org/dw/olson_fdaeir_20050722.pdf (accessed 1 June 2015).
8.
National Bioethics Advisory Commission. Ethical and Policy Issues in Research Involving Human Participants2001; Vol 1, Rockville, MD: US Government Printing Office.
9.
World Medical Association. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects, France: World Medical Association, 2013. www.wma.net (accessed 1 June 2015).
10.
ISO 14155:2011. Clinical investigation of medical devices for human subjects—Good clinical practice, 2011, Section 3.44.
11.
Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada. Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, Ottawa, Canada: Author, 2010.
12.
Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Biomedical Research Involving Human Subjects. 2002 Guideline 13, Geneva: CIOMS, 2002.
13.
Department of Veterans Affairs. VA Handbook 1200.05 Section 45, Washington, DC: Department of Veterans Affairs, 2014.
14.
45 CFR 46, Subpart A.
15.
21 CFR 50.
16.
21 CFR 56.
17.
National Institutes of Health. NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects, Bethesda, MD: National Institutes of Health, 1998.
18.
Pediatric Research Equity Act 2003.
19.
Best Pharmaceuticals for Children Act 2002.
20.
Department of Veterans Affairs. VA Handbook 1200.05 Section 48, Washington, DC: Department of Veterans Affairs, 2014.
21.
45 CFR 46, Subpart D.
22.
21 CFR 50, Subpart D.
23.
21 CFR 50.3(k).
24.
45 CFR 46.102(i).
25.
ShahSWhittleAWilfondB. How do institutional review boards apply the federal risk and benefit standards for pediatric research?J Am Med Assoc2004; 291: 476–482.
26.
KonA. Real pragmatism, kids, and the Clinical and Translational Science Award (CTSA). Am J Bioeth2008; 8: 45–47.
27.
Department of Defense Instruction 3216.02.
28.
Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Biomedical Research Involving Human Subjects. 2002 Guideline 14, Geneva: CIOMS, 2002.
29.
45 CFR 46.409.
30.
21 CFR 50.56.
31.
45 CFR 46 Subpart B.
32.
45 CFR 46.205(d).
33.
45 CFR 46.205(c).
34.
45 CFR 46.205(b).
35.
Civil Rights Act of 1964 (Pub. L. 88-352) (Title VII).
36.
Pregnancy Discrimination Act of 1978, (Pub.L. 95-555).
37.
AlleseeLGallagherCM. Pregnancy and protection: the ethics of limiting a pregnant woman’s participation in clinical trials. J Clin Res Bioeth2011; 2. DOI:10.4172/2155-9627.1000108.
38.
58 FR 39406 [July 22, 1993].
39.
ICH. General Considerations for Clinical Trials (ICH E8) Section 3.1.4.3, Geneva: ICH, 1997.
40.
ICH. Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting (ICH E2D) Section 5.4.1, Geneva: ICH, 2003.
41.
Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Biomedical Research Involving Human Subjects. 2002 Guideline 17, Geneva: CIOMS, 2002.
42.
21 CFR 201.57(c).
43.
Department of Veterans Affairs. VA Handbook 1200.05 Section 46, Washington, DC: Department of Veterans Affairs, 2014.
44.
45 CFR 46.204(a).
45.
45 CFR 46.204(c).
46.
45 CFR 46.204(b).
47.
45 CFR 46.204(e).
48.
45 CFR 46.204(h).
49.
45 CFR 46.204(i).
50.
45 CFR 46.204(j).
51.
Department of Veterans Affairs. VA Handbook 1200.05 Section 49, Washington, DC: Department of Veterans Affairs, 2014.
52.
Work Group on PTSD and Vulnerable Populations in Research. Should veterans with a diagnosis of post-traumatic stress disorder be considered a vulnerable population for the purpose of applying guidelines for the protection of human subjects in research? Report of a Work group convened by the National Center for Ethics in Health Care of the Veterans Health Administration on Behalf of the Secretary of Veterans Affairs. October 2008. Washington, DC: Department of Veterans Affairs.
53.
Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Biomedical Research Involving Human Subjects. 2002 Guideline 15, Geneva: CIOMS, 2002.
54.
SACHRP Summary.
55.
National Bioethics Advisory Commission. Research Involving Persons with Mental Disorders that may Affect Decisionmaking Capacity, Rockville, MD: US Government Printing Office, 1998.
56.
ICH E6 Good Clinical Practice.
57.
ISO 14155:2011. Clinical investigation of medical devices for human subjects—Good clinical practice, 2011.
58.
PalmerBWSalvaGNRoeschSC. Changes in capacity to consent over time in patients involved in psychiatric research. Br J Psychiatr2013; 202: 454–458.
59.
RenoldEHollandSRossNJ. ‘Becoming Participant’ Probematizing ‘Informed Consent’ in participatory research with young people in care. Qual Soc Work2008; 7: 427–447.
60.
PalmerBWJesteDV. Relationship of individual cognitive abilities to specific components of decisional capacity among middle-aged and older patients with schizophrenia. Schizophr Bull2006; 32: 98–106.
61.
DunnLBNowrangiMAPalmerBW. Assessing decisional capacity for clinical research or treatment: a review of instruments. Am J Psychiatr2006; 163: 1323–1334.
62.
SrebnikDSRutherfordLTPetoT. The content and clinical utility of psychiatric advance directives. Psychiatr Serv2005; 56: 592–598.
US Food and Drug Administration. Guidance for Industry: Suicidal ideation and behavior: Prospective assessment of occurrence in clinical trials. Rockville, MD: US Department of Health and Human Services, 2012.
65.
CrosbyAOrtegaLMelansonC. Self-Directed Violence Surveillance: Uniform Definitions and Recommended Data Elements, Version 1.0, Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2011.
