Protection of human subjects: Is expansive regulation counter-productive?

Northwestern University Law Review

Volumn 101, Issue 2, 2007, Pages 707-721

  Charrow, Robert ^a  

^a LLP   (United States)

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EID: 34547959620     PISSN: 00293571     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (88)

1. Compare The American Association of the Advancement of Science, Scientific Freedom, Responsibility and Law, http://www.aaas.org/spp/sfrl/ projects/stem/index.shtml (last visited Oct. 15, 2006), with President Discusses Stem Cell Research, http://www.whitehouse.gov/news/releases/2001/08/ 20010809-2.html (last visited Oct. 15, 2006).
2. See 45 C.F.R. pt. 46 (2006); 21 C.F.R. pts. 50, 56 (2006).
3. The regulatory system does not apply to certain types of research including, by way of example, educational testing research (for example, the College Board evaluating questions for a future LSAT as part of a current examination), observations of elected or appointed government officials, and studies of consumer preferences for various foods. See 45 C.F.R. § 46.101 (b) (2000).
4. Id.
5. See Office for Human Research Protections, http://www.hhs.gov/ ohrp/about/ohrpfactsheet.pdf.
6. See Darke v. Estate of Isner, 20 Mass. L. Rptr. 419, 2005 WL 3729113 (Mass. Supp. 2005);
7. L.C. BECKER ET AL., REPORT OF INTERNAL INVESTIGATION INTO THE DEATH OF A VOLUNTEER RESEARCH SUBJECT (Johns Hopkins University Report, July 16, 2001), available at http://www.hopkinsmedicine.org/press/2001/July/ report_of_internal_investigation.htm;
8. M. Milford, Lawsuits Attack Medical Trials, 23 THE NAT'L L.J., Aug. 27, 2001, at Al;
9. J. Washburn, Informed Consent, WASH. POST, Dec. 30, 2001, at W16;
10. see also Grimes v. Kennedy Krieger Inst, 782 A.2d 807, 856 (Md. 2001) (environmental research funded by the EPA);
11. Philip J. Hilts, A Second Death Linked to Gene Therapy, N.Y. TIMES, May 4, 2000, at A-20. One of the early instances of a death in an apparently healthy volunteer occurred at the National Institutes of Health in 1980.
12. See Gina B. Kolata, NIH Shaken by Death of Research Volunteer, 209 SCIENCE 475, 475-76 (1980).
13. See Grimes, 782 A.2d at 849-51.
14. See Robert Charrow & Jason Ross, Institutional Review Boards - Are They Science's Answer to Hollywood's Hays Board?, 5 MED. RES. L. & POL'Y REP. 469 (2006).
15. Many significant issues relating to IRBs-in addition to the ones discussed in this paper-are being debated in academia and in government. My failure to discuss them merely reflects space limitations and does not imply that I view those issues as unimportant. Thus, whether IRBs should be certified by independent accrediting bodies, whether financial conflict of interest rules should be strengthened, and whether the HIPAA privacy rule will adversely affect researchers are important issues that merit attention. There is one issue, though, that I view as unimportant: whether there should be a single government-wide agency to oversee human research. See ELISA EISEMAN, NATIONAL BIOETHICS ADVISORY COMMISSION: CONTRIBUTING TO PUBLIC POLICY 116 (2003). The President's National Bioethics Advisory Commission recommended a single regulatory agency. Id. A super-agency is unnecessary, in my view, especially since the vast bulk of clinical research is already under the regulatory aegis of the Secretary of Health and Human Services.
16. Mengele's "research" was ostensibly aimed at isolating and eradicating inferior genetic strands from the population as a way of creating a German super-race. See Richard S. Saver, Medical Research and Intangible Harm, 74 U. CIN. L. REV. 941, 951-52 (2006), and sources cited therein.
17. The NIH appropriation went from approximately $2.4 million in 1945 to over $873 million in 1966. See NIH Almanac, available at http://permanent.access.gpo.gov/lps5371/2003/almanac2003-4.pdf.
18. Pub. L. No. 87-781, § 102, 76 Stat. 780, 781-82 (1962).
19. H.K. Beecher, Ethics and Clinical Research, 274 N. ENG. J. MED. 1354, 1355 (1966).
20. In all, Beecher identified 50 studies (including the 12 noted above) that, in his view, raised serious ethical concerns. "[F]or reasons of space," he was only able to summarize 22 of those studies. Id. at 1355.
21. Jean Heller, Syphilis Victims in U.S. Study Went Untreated for 40 Years, N.Y. TIMES, July 26, 1972, at A1.
22. National Research Service Award Act of 1974, Pub. L. No. 93-348, § 212, 88 Stat. 342, 352-53 (1974);
23. see S. REP. No. 93-381 (1973). A year before congressional action, the then Department of Health, Education, and Welfare issued a proposed rule (dubbed "proposed policy") which sought to codify, for the first time, prior NIH policy for protecting human subjects in NIH funded research.
24. See Protection of Human Subjects, 38 Fed. Reg. 27,882 (Oct. 9, 1973). The HEW rule, which was to be codified at 45 C.F.R. part 46, was to govern all research programs funded by HEW. Id. A final rule was issued the following year. See Protection of Human Subjects, 39 Fed. Reg. 18,914 (May 30, 1974).
25. Pub. L. No. 95-622, §1801, 92 Stat. 3412, 3438-39 (1978).
26. See Protection of Human Subjects, 47 Fed. Reg. 13,272, 13,274 (March 29, 1982). Normally, federal regulation of grants and contracts is exempt from the normal notice and comment requirements of the Administrative Procedure Act. See 5 U.S.C § 553(a)(2). However, the Secretary of Health and Human Services voluntarily agreed to abide by the notice and comment requirements even when requirements would not apply. See Public Participation in Rule Making, 36 Fed. Reg. 2532 (proposed Feb. 5, 1971);
27. see also Humana of S.C v. Mathews, 419 F. Supp. 253, 260 (D.D.C. 1976) (holding in dictum that the Richardson waiver is binding on the Secretary).
28. See Model Federal Policy for Protection of Human Subjects, 51 Fed. Reg. 20,204 (June 3, 1986) (hereinafter Common Rule).
29. The most widely referenced codification of the Common Rule is the one issued by HHS, the largest funder of biomedical research. See 45 C.F.R. pt. 46 (2006).
30. There used to be an extraordinarily convoluted system by which a putative grantee assured NIH that it was complying or would comply with the Common Rule. Entities could file any one of a number of different types of assurances. That system is being replaced by a single Federalwide Assurance that provides grantees with significantly more flexibility than the Byzantine system it replaces. Research Projects Involving Human Subjects, 66 Fed. Reg. 19,141 (Apr. 13, 2001).
31. See 45 C.F.R. § 46.107 (2006).
32. See 45 C.F.R. § 46.110 (2006);
33. Research Activities Which May Be Reviewed Through Expedited Review, 46 Fed. Reg. 8392 (Jan. 26, 1981) (listing ten types of research that automatically qualify for expedited review).
34. See 45 C.F.R. § 46.116 (2006).
35. See 45 C.F.R. § 46.115(b) (2006).
36. See 45 C.F.R. pt. 689 (2005).
37. OHRP replaced the Office for Protection Against Research Risks ("OPRR"), which had been part of the National Institutes of Health. See Statement of Organization Functions, and Delegation of Authority, 65 Fed. Reg. 37,136 (proposed June 13, 2000). OHRP, as was the case for OPRR, is burdened with an overly bureaucratic, noun-string name.
38. 45 CF.R. § 46.123(a) (2006).
39. See OHRP, INSTITUTIONAL REVIEW BOARD GUIDEBOOK ch. I, at 10 (1993), available at http://ccnmtl. columbia.edu/projects/rcr/rcr_conflicts/misc/Ref/OHRP_IRB.pdf; 45 C.F.R. pt. 76 (2005).
40. See Robert Charrow, Wheat, Guns and Science: The Commerce Clause and Human Subjects, 9 J. NIH RES. 55, 56 (1997);
41. Robert Charrow, Whose Tissue Is It Anyway?, 6 J. NIH RES. 79, 79-80 (1994);
42. Robert Charrow, Informed Consent: From Canterbury Tales to Canterbury v. Spence, 5 J. NIH RES. 75, 80 (1993).
43. See U.S. CONST, art. I, § 8, cl. 1; South Dakota v. Dole, 483 U.S. 203, 212 (1987) (upholding, as a valid exercise of federal authority under the Spending Clause, a federal law that conditioned the receipt of federal highway funds on the State's adoption of a minimum drinking age of 21). The National Research Service Award Act of 1974, the statutory basis for the regulation of human subjects research at HHS, hinges receipt of federal funds on a grantee's assurance that it will conduct the federally funded research in accordance with the rules adopted by the Secretary.
44. See Pub. L. No. 93-348, §472, 88 Stat. 342 (1974) (codified at 42 U.S.C §289(a) (2000)).
45. U.S. CONST, art. I, § 8, cl. 3.
46. See United States v. Lopez, 514 U.S. 549, 556-57 (1995) (invalidating a federal law banning guns within a school zone as not sufficiently tied to interstate commerce);
47. United States v. Morrison, 529 U.S. 598, 618-19 (2000) (invalidating federal law creating private right of action for gender-based violence as lacking a foundation under the Commerce Clause). But see Gonzales v. Raich, 545 U.S. 1, 22 (2005) (overturning California's Compassionate Use Act, which authorized limited marijuana use for medicinal purposes even though the marijuana at issue was entirely intrastate).
48. 21 U.S.C. § 321 (p) (2000).
49. See 21 U.S.C. §§ 351-352 (2000).
50. See 21 U.S.C. § 331(a)-(c) (2000).
51. 21 U.S.C. § 355(i) (2000).
52. See FDA Form 1572, available at http://www.fda.gov/opacom/ morechoices/fdaforms/FDA-1572.pdf. Those seeking to sponsor an investigation trial must file an Investigational New Drug ("IND") application (for drugs and biologies) or Investigational Device Exemption ("IDE") application (for devices). See Investigational New Drug Application, 21 C.F.R. pt. 312, subpt. B (2006); 21 C.F.R. pt. 812 (2006).
53. See Recombinant DNA Research, 65 Fed. Reg. 77,655 (proposed Dec. 12, 2000).
54. See 21 C.F.R. pts. 50, 54, 56, 812 (2006).
55. 45 CF.R. § 46.103(b)(5)(i) (2006).
56. See 21 CF.R. § 312.64(a).
57. See 21 C.F.R. § 312.32(c)(1)(A)-(c)(2).
58. See 21 CF.R. § 312.32(a).
59. See 21 C.F.R. § 312.32(c)(1)(B).
60. See 21 C.F.R. § 312.33(b)(1)-(4).
61. FDA is authorized by the Federal Food, Drug, and Cosmetic Act to inspect sites that conduct clinical trials. See 21 U.S.C §§ 372-374 (2000). Investigators are obligated to permit such inspections. Id. FDA inspectors record their observations on Form 483. The form is provided to the researcher at the end of the inspection. Inasmuch as the data collected from a clinical trial of a new drug will be used by the sponsor to support a New Drug Application, the FDA normally inspects patient records at sites that have enrolled relatively large numbers of patients to ensure the accuracy of data and compliance with FDA rules.
62. See Martin Shapiro and Robert Charrow, Scientific Misconduct in Investigational Drug Trials, 312 N. ENG. J. MED. 731, 732 (1985).
63. See 21 C.F.R. § 312.70(a).
64. See S. 193, 105th Cong. (1997).
65. See H.R. 5578, 109th Cong. (2006);
66. H.R. 4605, 106th Cong. (2000).
67. See United States v. Morrison, 529 U.S. 598, 617 (2000) (rejecting the argument that "Congress may regulate noneconomic, violent criminal conduct based solely on that conduct's aggregate effect on interstate commerce").
68. See DEP'T OF HEALTH & HUMAN SERVS., FEDERALWIDE ASSURANCE OF PROTECTION FOR HUMAN SUBJECTS 4 (2002).
69. See Trustees of Dartmouth College v. Woodward, 17 U.S. (4 Wheat.) 518, 627 (1819).
70. See RESTATEMENT (SECOND) OF CONTRACTS §§ 71, 90 (1979).
71. National Research Service Award Act of 1974, Pub. L. No. 93-348, § 212, 88 Stat. 342, 352-53 (amending the Public Health Service Act by adding a new section 474).
72. Health Research Extension Act of 1985, Pub. L. No. 99-158, § 491, 99 Stat. 820, 861-62 (codified at 42 U.S.C § 289(b)(2) (2000)) (emphasis added) (amending the Public Health Service Act by adding a new subjection (b) to existing section 474).
73. 31 U.S.C. § 1341(a)(1)(A) (2000).
74. See Cherokee Nation of Oklahoma v. Leavitt, 543 U.S. 631, 642 (2005);
75. Star-Glo Assoc, LP v. United States, 414 F.3d 1349, 1354 (Fed. Cir. 2005);
76. cf. E.I. Du Pont De Nemours & Co. v. United States, 365 F.3d 1367, 1374 (Fed. Cir. 2004) (discussing, without deciding, whether the Anti-Deficiency Act prohibits the government from agreeing to an open-ended indemnification).
77. 733 F. Supp. 1002, 1002-03 (D. Md. 1990).
78. See 5 U.S.C. §§ 600-612 (2000).
79. See 2 U.S.C. §§ 1501-1571 (2000).
80. 45 C.F.R. § 46.102(d) (2006).
81. 500 U.S. 173 (1991).
82. Id. at 200 (citing Keyishian v. Board of Regents, 385 U.S. 589, 605-06 (1967)).
83. Compare IMMANUEL KANT, CRITIQUE OF PURE REASON (Robert Hutchinson ed., J.M.D. Meiklejohn trans., Encyclopedia Britannica 1989) (1781), KARL R. POPPER, THE LOGIC OF SCIENTIFIC DISCOVERY (rev. ed. 1972), and FRANCIS BACON, THE NEW ORGANON OR TRUE DIRECTIONS CONCERNING THE INTERPRETATION OF NATURE (1620) (James Spedding et al. trans., 1863), with Common Rule, supra note 19, at 20,206. "It is probably impossible to spell out cogently in a few sentences what we mean by scientific research. The Common Rule is a testament to the notion that not all ideas can be reduced to a few sentences." Charrow & Ross, supra note 8, at 472.
84. See Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579 (1993).
85. See 45 C.F.R. § 46.116 ("[N]o investigator may involve a human... as a subject... unless the investigator has obtained the legally effective informed consent....").
86. See U.S. FOOD & DRUG ADMIN., INFORMATION SHEETS, GUIDANCE FOR I NSTITUTIONAL REVIEW BOARDS AND CLINICAL INVESTIGATORS: 1998 UPDATE, at 9 (1998) ("[I]nformed consent must be obtained prior to initiation of any clinical procedures [including screening tests] that are performed solely for the purpose of determining eligibility for research...." (emphasis added)).
87. See Charrow & Ross, supra note 8, at 472;
88. Philip Hamburger, The New Censorship: Institutional Review Boards, 2004 SUP. CT. REV. 271, 290.