The regulation of MR neuroimaging research: Disentangling the Gordian knot

American Journal of Law and Medicine

Volumn 33, Issue 2-3, 2007, Pages 295-317

  Kulynych, Jennifer J ^a,b  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FINANCIAL MANAGEMENT; FOOD AND DRUG ADMINISTRATION; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HUMAN; MEDICAL INFORMATION; MEDICAL RESEARCH; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; PRACTICE GUIDELINE; REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS;

EID: 34548736488     PISSN: 00988588     EISSN: None     Source Type: Journal    
DOI: 10.1177/009885880703300207     Document Type: Review

References (137)

1. Contraindications are factors that render a medical procedure or treatment inadvisable. A primary contraindication of MRI, due to the risk of trauma, heat-related injury, and device failure, is the presence in the body of metal fragments or of objects, such as implanted medical devices with metal components (e.g., aneurysm clips or pacemakers), unless such devices have been previously determined to be MRI-compatible. See U.S. Food and Drug Administration, CDRH Working Group, A Primer on Medical Device Interactions with Magnetic Resonance Systems (Feb. 7, 1997) (draft version), available at http://www.fda.gov/cdrh/ode/primerf6.html.
2. In some research protocols the MRI procedure may include the intravenous injection of a contrast agent to enhance the visual appearance of fluid and tissue. For a very basic explanation of MRI scanning, see the National Library of Medicine MedlinePlus Medical Encyclopedia: MRI, available at http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm.
3. Incidents of MRI-related harm reported to the U.S. Food and Drug Administration include excessive tissue heating and first, second, and third degree burns related to equipment failure, use of external accessories/objects, or equipment malfunction, as well as injuries and deaths associated with impact injury from ferromagnetic metal objects improperly introduced within the MRI scanning environment. See generally Institute for Magnetic Resonance Safety, Education, and Research, http://www.imrser.org; http://www.MRIsafety.com (summarizing literature and providing citation to scientific articles on heating and impact injuries).
4. See also, FDA Medical Device Reports (MDR) Database, http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMDR/Search.cfm;
5. FDA Center for Devices and Radiological Health, MRI Safety, http://www.fda.gov/cdrh/safety/mrisafety.html (describing death of six year old boy undergoing MRI due to injury from the impact of ferromagnetic oxygen tank improperly permitted in the vicinity of the MRI magnet).
6. See, e.g., Catherine D. Zick, Charles Mathews, et al., Genetic Testing for Alzheimer's Disease and its Impact on Insurance Purchasing Behavior, 24 HEALTH AFFAIRS 2 (2005), 483-490 (examining impact of testing for Alzheimer's disease risk on patients' insurance purchasing behavior and the resultant risk of discrimination by insurers).
7. E.g., the use of MRI technology for the purpose of lie detection, the prediction of future violence, or detection of chronic pain.
8. A mythological knot tied by Gordius, king of Phyrgia, was so complex that prophecy held it could only be untied by the future king of Asia. Alexander the Great fulfilled the prophesy by resolving the knot with an innovative solution. Webster's New Encyclopedic Dictionary 793 (2002) (entry for "Gordian knot"). "Gordian knot" is a metaphorical expression for a problem that is "intricate" or "insoluable" on its own terms. Id.
9. This non-exhaustive list focuses narrowly on those regulations that pertain directly to the use of the MRI scanner in FDA-regulated research or other research involving human subjects. Other federal requirements applicable to research generally (e.g., regulations governing the expenditure of federal grant funds, policies for billing clinical research procedures to Medicare and Medicaid, regulations pertaining to scientific misconduct), are potentially implicated as well, though discussion of them is beyond the scope of this article. In addition to federal regulations, state common law, statutes, and regulations may also govern certain aspects of human subjects research.
10. See Investigational Device Exemptions, 21 C.F.R. § 812 (2005).
11. See Protection of Human Subjects, 21 C.F.R. § 50 (2005); Institutional Review Boards, 21 C.F.R. § 56 (2005).
12. See Protection of Human Subjects, 45 C.F.R. § 46 (2006). Basic Common Rule requirements have been adopted by a number of other federal agencies that conduct or fund research.
13. See General Administrative Requirements, 45 C.F.R. § 160 (2006); Security and Privacy 45 C.F.R. § 164 (2006).
14. See Policies of General Applicability, 42 C.F.R. § 50 (2006); Financial Disclosure by Clinical Investigators 21 C.F.R. § 54 (2006). The PHS includes the National Institutes of Health, the Centers for Disease Control and Prevention, the Office of the DHHS Assistant Secretary for Health, and several other DHHS components.
15. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321(h)(2) (2006) (defining "device" as an object intended for use in the diagnosis of disease or other conditions). This definition includes an "instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is . . . intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals . . ." 21 U.S.C. §321(h)(2) (2006).
16. These FDA regulations include requirements for pre-market approval or clearance, good manufacturing practices, device reporting, and establishment registration. See 21 C.F.R. Parts 803,807,814, and 820.
17. Classification, which is based upon device risk, determines the type of submission (for pre-market notification versus pre-market approval) that a manufacturer must make to FDA to market a device. Class I and II devices that are not specifically exempt generally require clearance via pre-market notification only; an MRI scanner is a Class II device subject to pre-market notification requirements that must also meet specific product performance standards. 21 C.F.R. § 892.1000 (2006). To make significant changes (or changes that could alter the risk or effectiveness profile) to an MRI scanner or to its product labeling or other descriptions of intended use or indication, a manufacturer of an MRI must generally seek premarket approval. On the other hand, a modification to a scanner or other device, if made solely for the care of an individual patient upon orders of a physician, is generally considered to result in a "custom" device that is not subject to pre-market notification or approval. 21 C.F.R. § 812.3(b) (2006). FDA device regulations pertaining to device manufacturing, quality control, labeling, and post-market reporting are beyond the scope of this paper.
18. See 21 C.F.R. §807, Subpart E (2006). Such modifications might include new scanner software systems or magnets of a greater field strength than those currently marketed. Very minor modifications that do not affect device safety or effectiveness may not require premarket clearance.
19. See 21 C.F.R. § 814 (2006). An example of a new indication might be a revision to the labeling to reflect a claim that an MRI system can detect a specific brain disorder (versus a claim that it is useful for general medical imaging purposes). For a detailed discussion of the regulatory implications of modifying a medical device, see John J. Smith, Regulatory and Legal Implications of Modifying FDA-approved Medical Devices, 11 INTERVENTIONAL RADIOLOGY PRACTICE 19 (2000).
20. Investigational Device Exemptions, 21 C.F.R. § 812.2 (2006) (stating the scope and applicability of the FDA's Investigational Device Exemptions).
21. 21 C.F.R. §§ 812.2(c)(1), 812.2(c)(4) (2006). These studies are sometimes referred to as "IDE-exempt" studies.
22. Even when a study is IDE-exempt because the device studied is used in accordance with its approved labeling, if the purpose of the study is to collect safety or efficacy data (sometimes called "performance" data), the FDA's human subjects regulations would still apply.
23. Investigational Device Exemptions, 21 C.F.R. § 812.3 (2006).
24. The study sponsor should provide the IRB with the rationale for the NSR claim. If the IRB concurs with the sponsor's risk assessment, the study may begin without submission of an IDE application to FDA. Investigational Device Exemptions, 21 C.F.R. § 812.2(b)(ii) (2006) (stating the applicability of the FDA's Investigational Device Exemptions).
25. Investigational Device Exemptions, 21 C.F.R. § 812.20 (2006). The FDA generally considers the use of MRI in a clinical investigation to involve significant risk when the main static magnetic field is greater than 8 tesla (or 4 tesla for infants aged < 4 mos.), or when other operating conditions such as specific absorption rate (SAR) or sound pressure levels exceed parameters specified in FDA guidance. See FDA CDRH, Guidance for Industry and FDA Staff, Criteria for Significant Risk Investigations of Magnetic Resonance Devices, www.fda.gov (last visited July 6, 2007).
26. Investigational Device Exemptions, 21 C.F.R. § 812.3(m) (2006) (defining "significant risk" as one with the potential for serious risk to the health, safety, or welfare of a subject).
27. Investigational Device Exemptions, 21 C.F.R. § 812.150 (2006) (stating FDA reporting criteria).
28. Regulatory interpretation conveyed via personal email communication to the author from Elisa Harvey, D.V.M., Ph.D., Director, IDE and HDE Programs, Office of Device Evaluation, Center for Devices and Radiological Health, FDA, Aug. 16, 2006. Where a scanner is not studied for a purpose related to treatment or diagnosis, it might also be argued that the scanner is not a medical device within the meaning of the statutory definition.
29. Protection of Human Subjects, 21 C.F.R. § 50.1 (2006) (stating the scope of the FDA's protection of human subjects regulations); Institutional Review Boards, 21 C.F.R. § 56.101 (2006) (stating the scope of the FDA's Institutional Review Board regulations).
30. Protection of Human Subjects, 21 C.F.R. § 50.1 (2006); Institutional Review Boards, 21 C.F.R. § 56.101 (2006).
31. Protection of Human Subjects, 21 C.F.R. § 50.3(c) (defining clinical investigation) (2006); Institutional Review Boards, 21 C.F.R. § 56.102(c) (2006) (defining clinical investigation).
32. Id.
33. Institutional Review Boards, 21 C.F.R § 56.110 (2006). Expedited review of a research protocol may be conducted by the IRB chair (or chair's designee) and does not require deliberation by the entire IRB. Id.
34. These circumstances include the following: when use of an investigational product meets regulatory criteria for an "emergency use;" when the IRB finds that the research meets strict criteria for "planned emergency use;" when the President makes findings necessary to waive prior consent for the administration of an investigational drug to military personnel; and, pursuant to a 2006 "interim final rule," when an investigational in vitro diagnostic device is used in specific circumstances, without prior consent, to identify the causative agent in a public health, nuclear, chemical or bioterrorism emergency. In 2006 FDA's Center for Devices and Radiological Health also issued guidance indicating that it would exercise "enforcement discretion" with respect to studies of in vitro diagnostic devices conducted without consent, where the "human subject" consists of de-identified stored tissue. See 21 C.F.R. §§ 50.23, 50.24 (2006); see also, Food and Drug Administration, Medical Devices; Exception from General Requirements for Informed Consent, 71 Fed. Reg. 109, 32827 (June 7, 2006).
35. Protection of Human Subjects, 21 C.F.R. §§ 50.50-50.56 (2006). For discussion of 45 C.F.R. pt. 46, subpt. D, see supra Section II.C.
36. For discussion of 45 C.F.R. pt. 46, subpt. B, see supra Section II.C.
37. Institutional Review Boards, 21 C.F.R. § 56.108 (2006).
38. Investigational Device Exemptions, 21 C.F.R. § 812.150(b) (2006).
39. U.S. Food and Drug Administration, Guidance for Institutional Review Boards and Clinical Investigators 1998 Update, app. E, available at http://www.fda.gov/oc/ohrt/irbs/appendixe.html (significant Differences in FDA and HHS Regulations for Protection of Human Subjects).
40. Such research might also be regulated if conducted in one of a small number of states (e.g., Maryland) that have enacted clinical research legislation, or in a state whose medical records confidentiality laws regulate the disclosure of medical record information for research. See, e.g., MD. CODE ANN., HEALTH-GEN. § 13-2001 et seq. (2005) (human subjects research, enacted 2002); MD. CODE ANN., HEALTH-GEN. §§ 4-301(g), 4-305(b)(2)(i) (2005) (disclosure of medical records for research). The Maryland human subjects research legislation is relatively recent and it is unclear to what extent the state will attempt to enforce it, particularly with respect to secondary data studies.
41. These agencies or departments and their relevant regulations are: Department of Agriculture, see 7 C.F.R. § 1c (2005); Central Intelligence Agency, see Exec. Order No. 12333, 46 Fed. Reg. 59,941 (Dec. 8, 1981); Department of Commerce, see 15 C.F.R. § 27 (2004); Department of Consumer Product Safety, see 16 C.F.R. § 1028 (2006); Department of Defense, see 32 C.F.R. § 219 (2006); Department of Education, see 34 C.F.R. § 97 (2005); Department of Energy, see 10 C.F.R. § 745 (2006); Environmental Protection Agency, see 40 C.F.R. § 26 (2006); Department of Health and Human Services, see 45 C.F.R. §§ 46.101-46.124 (2006); Department of Housing and Urban Development, see 24 C.F.R. § 60 (2006); Department of International Development, see 22 C.F.R. § 225 (2005); Department of Justice, see 28 C.F.R. §§ 46, 512, pt. 22 (2006); National Aeronautics and Space Administration, see 14 C.F.R. § 1230 (2006); National Science Foundation, see 45 C.F.R. § 690 (2006); Social Security Administration, see Pub. L. No. 103-296; Department of Transportation, see 49 C.F.R. § 11 (2006); Department of Veterans Affairs, see 38 C.F.R. §§ 16, 17.85 (2006). Several other agencies also employ 45 C.F.R. §§ 46 subpts. B, C, and D (2006).
42. See 45 C.F.R. [SUBCH. A] § 1 (2006).
43. See generally, 45 C.F.R. pt. 46 (2006).
44. Id.
45. Basic HHS Policy for the Protection of Human Research Subjects, 45 C.F.R. § 46.101 (2006).
46. Basic HHS Policy for the Protection of Human Research Subjects, 45 C.F.R. § 46.103 (2006) (outlining required compliance assurances).
47. Any institution that does not elect to apply the Common Rule to otherwise unregulated research must nonetheless specify in its assurance the principles that it will follow in the oversight of such research. Basic HHS Policy for the Protection of Human Research Subjects, 21 C.F.R. § 46.103(b)(1) (2006).
48. See 45 C.F.R. pt. 46 subpt. D (2006); 21 C.F.R. pt. 50 subpt D (2006) (the National Science Foundation, which also funds basic MRI and cognitive neuroscience research, has adopted Subpart A, but not Subpart D). See generally NATIONAL SCIENCE FOUNDATION, FREQUENTLY ASKED QUESTIONS AND VIGNETTES: INTERPRETING THE COMMON RULE FOR THE PROTECTION OF HUMAN SUBJECTS FOR BEHAVIORAL AND SOCIAL SCIENCE RESEARCH, http://www.nsf.gov/bfa/dias/ policy/hsfaqs.jsp (last visited April 3, 2007).
49. See 21 C.F.R. § 50.54 (2006).
50. See 21 C.F.R. § 50.53 (2006).
51. 45 C.F.R. § 46.407 (2006); 21 C.F.R. §50.54 (2006).
52. For example, a patient suffering from a neurological disorder or brain tumor might enroll in a study of an investigational drug intended to treat the patient's condition. The protocol for such a study might specify that MRI studies be performed as they normally would be in the course of clinical care to diagnose the disorder or to monitor the course of treatment.
53. Note that the possible detection of incidental brain abnormalities, as discussed in Section III.C of this article, is generally not a "benefit" for purposes of Subpart D review.
54. See 45 C.F.R. § 46.407 (2006); 21 C.F.R. § 50.54 (2006).
55. 45 C.F.R. §§ 46.201-46.207 (2006).
56. 45 C.F.R. § 46.204(b) (2006).
57. See CTR. DEVICES & RADIOLOGICAL HEALTH, U.S. DEP'T HEALTH & HUMAN SERV., GUIDANCE FOR THE SUBMISSION OF PREMARKET NOTIFICATIONS FOR MAGNETIC RESONANCE DIAGNOSTIC DEVICES (NOV. 14, 1998), available at http://www.fda.gov/cdrh/ode/mri340.pdf.
58. See, e.g., The University of Pennsylvania Health System Center for Advanced Magnetic Resonance Imaging and Spectroscopy Policy, Section 2: Human Studies and Safety http://www.mmrrcc.upenn.edu/CAMRIS/policy.manual.chapter2. shtml#pregnancy (last visited August 6, 2007).
59. Protection of Human Subjects, 45 C.F.R. §§ 46.201-46.207 (2006). See also, NIMH COUNCIL WORKGROUP ON MRI RESEARCH PRACTICES, MRI RESEARCH SAFETY AND ETHICS: POINTS TO CONSIDER (report of workgroup held on Sept. 14, 2005), available at http://www.nimh.nih.gov/council/mri- research-safety-ethics.pdf. Note: the author participated as a member of the Working Group.
60. See Privacy of Individually Identifiable Health Information, 45 C.F.R. pt. 164, subpt. E (2006).
61. The HIPAA statute includes as a covered entity any health care provider who engages in one of the enumerated HIPAA "standard transactions" that involve the electronic transmission of health information. See Health Insurance Portability and Accountability Act, Pub. Law. 104-191 (104th Congress), §1172(a) (Applicability). For example, providers who submit claims electronically (i.e., most providers) are covered entities.
62. 45 C.F.R. § 160.103 (2006).
63. 45 C.F.R. § 164.514(b)(2) (2006).
64. 45 C.F.R. § 164.514(b)(1) (2006).
65. Id.
66. Volumetric MRI datasets contain cross-sectional images of sufficient resolution that they may be used to produce three-dimensional images of external and external brain and skull features. Jennifer Kulynych, Legal and Ethical Issues in Neuroimaging Research: Human Subjects Protection, Medical Privacy, and the Public Communication of Research Results, 50 BRAIN & COGNITION 345, 353 (2002).
67. Surface rendering is used in research to reconstruct three-dimensional images of the cortical surface or of brain structures. See, e.g., J. Kulynych, K. Vladar, et al, Three-dimensional Surface Rendering in MRI Morphometry: A Study of the Planum Temporale, 17 J. COMP. ASSISTED TOMOGRAPHY 4, 529-35 (1993);
68. D.C. van Essen, A Population-Average, Landmark- and Surface-based (PALS) Atlas of Human Cerebral Cortex, 28 NEUROIMAGE 23, 635-62 (2005).
69. For further discussion of the identifiability of volumetric MRI datasets and a figure illustrating a potentially identifiable surface rendering of a human face, see Jennifer Kulynych, Legal and Ethical Issues in Neuroimaging Research: Human Subjects Protection, Medical Privacy, and the Public Communication of Research Results, 50 BRAIN & COGNITION 345, 353 (2002).
70. Kulynych, supra note 64, at 354-355.
71. Id. at 353 (discussing identifiability of volumetric MRI datasets and illustrating a potentially identifiable surface rendering of a human face).
72. See 45 C.F.R. § 164.508 (2006).
73. 45 C.F.R. § 164.512(i) (2006).
74. See, e.g., Jennifer Kulynych & David Korn, The Effect of the New Federal Medical Privacy Rule on Research, 346 NEW ENG. J. MED. 201, 203-04 (2002) (arguing that HIPAA's restraints on the use and disclosure of medical information for legitimate research purposes are excessive).
75. See Security Standards for the Protection of Electronic Protected Health Information, 45 C.F.R. pt. 164, subpt. C (2006).
76. Administrative Data Standards and Related Requirements, 45 C.F.R. § 164.104 (2006).
77. 45 C.F.R. § 164.103 (2006) (The Privacy Rule permits a single legal entity to carve out from covered status components of the entity that perform functions that, standing alone, would not be covered by the Rule).
78. 45 C.F.R. § 164.104 (2006) (providing that HIPAA's privacy restrictions apply only to covered entities).
79. Id.
80. See DHHS Statements of Delegation of Authority, 65 Fed. Reg. 250, 82381 (Dec. 28, 2000) (OCR); 68 Fed. Reg. 34, 8297 (Feb. 20, 2003) (CMS).
81. 45 C.F.R. pt. 46, subpt. A (2006); Privacy of Individually Identifiable Health Information, 45 C.F.R. pt. 64, subpt. E (2006).
82. 45 C.F.R. § 46.111(a)(7) (2006) (Criteria for IRB approval of research: adequate provisions for the protection of privacy and confidentiality).
83. 45 C.F.R. § 508 (2006) (Privacy Rule authorization requirements and implementation standards).
84. 45 C.F.R. § 164.508(b)(3)(i) (2006).
85. 45 C.F.R. §164.12(i)(2)(ii) (2006) (criteria for IRB review of privacy-specific risk to determine whether waiver of HIPAA authorization is permissible).
86. See, e.g., ASS'N OF AM. MED. COLLEGES, TASK FORCE ON FINANCIAL CONFLICTS OF INTEREST IN CLINICAL RESEARCH, PROTECTING SUBJECTS, PRESERVING TRUST, PROMOTING PROGRESS: POLICY AND GUIDELINES FOR THE OVERSIGHT OF INDIVIDUAL FINANCIAL INTERESTS IN HUMAN SUBJECT RESEARCH 3 (2001), http://www.aamc.org/research/coi/firstreport.pdf.
87. Financial Disclsoure by Clinical Investigators (FDA), 21 C.F.R. § 54.4 (2006) (for DHHS funded or supported research); 42 C.F.R. § 50.604 (2006).
88. Reports of financial interests made to regulators (DHHS or FDA) are treated as confidential under both regulations. Further, while DHHS regulations require grantee institutions to review investigators' financial interests prospectively, FDA regulations require disclosure to the agency only retrospectively, upon submission of a marketing application. Thus, the FDA's financial disclosure regulations have no potential to protect the subjects of the studies conducted to support the application and serve only to give the agency a basis to question the validity of study data submitted by the sponsor.
89. 42 C.F.R. § 50.602 (2006). See also, National Science Foundation, Investigator Financial Disclosure Policy, 60 Fed. Reg. 35820 (July 11, 1995). As noted previously, the PHS includes NIH, CDC, the Office of the DHHS Assistant Secretary for Health, and several other DHHS entities or constituent agencies.
90. 21 C.F.R. § 54.4(b) (2006) (responsibility of investigator to provide sponsor sufficient accurate information to permit sponsor to meet its financial disclosure obligations).
91. 42 C.F.R. §50.603 (2006) (definition of "significant financial interest"); 42 C.F.R. §§ 50.604, 50.605 (review of financial interests and management of conflicting financial interests).
92. 42 C.F.R. §§ 50.604-50.605 (2006).
93. 21 C.F.R. §54.4(a)(3) (2006) (requirements for sponsor disclosure of specified investigator financial interests).
94. 21 C.F.R. §§ 54.4-54.5 (2006).
95. 21 C.F.R. § 54.1 (sponsor must disclose investigator financial information upon submission of the marketing application; FDA may reject the data already gathered for the submitted studies if appropriate steps "have not been taken" by the sponsor to minimize investigator bias).
96. Although federal regulations require institutions to review only the financial interests of researchers engaged in federally-funded research, and these regulations exclude researchers engaged in studies funded through the Small Business Innovation and Research (SBIR) and Small Business Technology Transfer (SBTTR) programs, 42 C.F.R. § 50.602 (2006), many research institutions now require all employed researchers to make annual financial disclosures.
97. California, which regulates research directly through its Protection of Human Subjects in Medical Experimentation Act, does require that participants in "medical experiments" be informed of the material financial interests of both the investigator and the research institution. "Medical experimentation" includes much drug and device research that is investigational or is not intended to benefit the subject. See CAL. HEALTH & SAFETY CODE § 24170 (2006).
98. If, however, the research were conducted in Maryland or California, the investigator would be required to comply with state laws pertaining to human subjects research. In Maryland, for instance, she would be required to obtain IRB review and informed consent for any research involving "human subjects" as defined in DHHS regulations. CAL. HEALTH & SAFETY CODE § 24170 (2006); MD. CODE ANN., HEALTH-GEN. §§ 13-2001-13-2004 (2006).
99. But see the aforementioned California and Maryland requirements, supra notes 94 and 38, respectively.
100. See 45 C.F.R. § 104(a)(3) (2006) (definition of a HIPAA covered entity, which includes a health care provider who transmits health information electronically in connection with one of the HIPAA standard transactions, such as billing).
101. Under HIPAA, academic institutions that own clinical entities such as hospitals, or whose medical or nursing school faculty derive revenue from clinical services are permitted to designate themselves as "hybrid" entities, restricting HIPAA coverage to those entities that engage in a HIPAA standard transactions. Id.
102. Id.
103. MRI facilities that perform scans for clinical purposes may have their safety procedures evaluated during various accreditation processes, and are more likely to employ MR technicians who are certified radiology technicians or have obtained specific MR certification. Research MR scanning performed in research facilities or after-hours in clinical facilities is less likely to involve personnel who have formal training or certification as MR technicians.
104. NIMH COUNCIL WORKGROUP ON MRI RESEARCH PRACTICES, supra note 57.
105. See id.
106. Publication of the final working group report is anticipated in the spring of 2007.
107. See generally, NIMH COUNCIL WORKGROUP ON MRI RESEARCH PRACTICES, supra note 57 and accompanying text.
108. Id.
109. 21 C.F.R. § 56.111(a)(1) (2006).
110. 45 C.F.R. pt. 46, subpt. D (2006); 21 C.F.R. pt. 50, subpt. D (2006).
111. Seema Shah et. al., How Do Institutional Review Boards Apply the Federal Risk and Benefit Standards for Pediatric Research?, 291 JAMA 476, 479 (2004).
112. See, e.g., id. at 476-482 (reporting that 48% of IRB chairpersons surveyed would categorize an MRI study performed without sedation as "minimal risk").
113. Id.
114. 45 C.F.R. § 46.406(c); 21 C.F.R. §50.53(c) (2006).
115. 45 C.F.R. § 46.407 (2006); 21 C.F.R. §50.54 (2006).
116. 21 C.F.R. § 50.20 (stating that consent must be obtained from the subject or the subject's legally authorized representative, defined in § 50.3(1) as an individual or entity authorized under applicable to consent on behalf of the prospective subject to the procedures involved in the research); 45 C.F.R. § 46.102(c) (defining legally authorized representative under DHHS regulations).
117. See OFFICE OF THE MARYLAND ATTORNEY GENERAL, POLICY STUDY ON ALZHEIMER'S DISEASE CARE 4, 9 (2004) (discussing the limitations of Maryland law authorizing surrogate consent for health care when applied to non-therapeutic research), available at http://www.oag.state.md.us/ Healthpol/alzchap4.pdf.
118. California is one of the few states to date to enact an informed consent law pertaining to research. It specifies when a surrogate may give consent for non-therapeutic medical research. See CAL. HEALTH & SAFETY CODE § 24178(e) (2006).
119. See, e.g., Scott Y.H. Kim, Paul S. Applebaum, et al., Proxy and Surrogate Consent in Geriatric Neuropsychiatric Research: Update and Recommendations, 161 AM. J. PSYCHIATRY 5, 797 (2004).
120. See Judy Illes, "Pandora's Box" of Incidental Findings in Brain Imaging Research, 2 NATURE CLINICAL PRAC. NEUROLOGY 60, 60 (2006) (citing to published research on incidental research imaging findings).
121. See Matthew Kirschen et al., Subjects' Expectations in Neuroimaging Research, 23 J. MAGNETIC RESONANCE IMAGING 205, 207 (2006).
122. Id. at 208-09.
123. See Judy Illes et al., Discovery and Disclosure of Incidental Findings in Neuroimaging Research, 20 J. MAGNETIC RESONANCE IMAGING 743, 746 (2004).
124. See 21 C.F.R. § 56.111(a)(1) (2006); 45 C.F.R. § 46.111(a)(1) (2006).
125. See Judy Illes et al., Incidental Findings in Brain Imaging Research, 311 SCI. 783 (2006) (reporting the views of the working group), available at http://www.sciencemag.org/cgi/content/full/311/5762/ 783?ijkey=dzAtfMjtfdrvU&keytype=ref&siteid=sci.
126. Id. at 783-84 (the group did not conclude that researchers have any affirmative duty to screen research participants for IFs).
127. See generally, Robert S. Olick and George R. Bergus, Malpractice Liability for Informal Consultations, 35 FAM. MED. 476 (2003) (discussing malpractice liability in informed consent situations);
128. Leonard Berlin, Curbside Consultations, 178 AM. J. ROENTGENOLOGY 1353 (2002) (concluding that the risk of malpractice liability for curbside consultations, while historically small, increases with the specificity and identifiability of the information exchanged and whether patient records or test results are reviewed by the consulting physician).
129. These concerns were identified during the 2005 meeting of the NIMH-sponsored working group on incidental findings, in which this author participated.
130. See, e.g., Jennifer Proctor, Responding to Restrictions on Research, AAMC REPORTER, April 2000, http://www.aamc.org/newsroom/ reporter/april2000/research.htm (describing the AAMC's new compliance efforts). The research compliance trade publication Medical Research Law and Policy Report (Bureau of National Affairs) was introduced in 2002 in response to demand for compliance information specific to clinical research.
131. See, e.g., Jeremy Sugarman et al., The Cost of Institutional Review Boards in Academic Medical Centers, 352 NEW ENG. J. MED. 17 (2005), 1825;
132. see also, Howard Dickler & David Korn, The Costs of Institutional Review Boards (letter) 353 NEW ENG. J. MED. 3 (2005), at 315 (arguing that Sugarman et al. actually underestimate research compliance costs).
133. See NAT'L BIOETHICS ADVISORY COMM'N, ETHICAL AND POLICY ISSUES IN RESEARCH INVOLVING HUMAN PARTICIPANTS, vol. 1, at 28 (2001).
134. See Research Revitalization Act of 2002, S. 3060, 107th Cong. (2002); Human Research Subject Protection Act of 2002, H.R. 4697, 107th Cong. (2002).
135. See id.
136. See NAT'L INST. OF HEALTH, CLINICAL RESEARCH POLICY ANALYSIS & COORDINATION COMM., HUMAN SUBJECTS REGULATIONS, available at http://crpac.od.nih.gov/ issue_Interp_Human_Subj_Regs.asp.
137. In a January 11, 2006 letter (to Capt. Michael Carome, Associate Director for Regulatory Affairs, DHHS Office of Human Research Protections), concerning new OHRP guidance on adverse event reporting, Jordan Cohen, M.D., President of the Association of American Medical Colleges, noted that in the six years since DHHS Secretary Shalala issued her call for harmonization of the human subjects protection regulations of the DHHS and the FDA, "disappointingly little has been accomplished to date." Letter from Jordan Cohen, M.D. to Michael Carome (Jan. 11, 2006), available at http://www.aamc.org/advocacy/ library/research/corres/2006/011106.pdf.