Litigation in Clinical Research: Malpractice Doctrines versus Research Realities

Abate T. , “Rules for Clinical Trials are Confusing, Inconsistent,” San Francisco Chronicle, August 5, 2002, at A-l, available at <http://www.sfgate.com/cgibin/article.cgi?f=/c/a/2002/08/05/MN47420.DTL>.

Morin K. Rakatansky H. Riddick F.A. Morse L. J. , “Managing Conflicts of Interest in the Conduct of Clinical Trials,” JAMA 287 (2002): 78–84, at 78.

Noah L. , “Informed Consent and the Elusive Dichotomy Between Standard and Experimental Therapy,” American Journal of Law & Medicine 28 (2002): 361–408, at 361.

Klein J.E. and Fleischman A.R. , “The Private Practicing Physician-Investigator: Ethical Implications of Clinical Research in the Office Setting,” Hastings Center Report 32, no. 4 (2002): 22–26, at 22–23.

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines/or the Protection of Human Subjects of Research (U.S. Department of Health, Education, and Welfare, Pub. No. [OS] 78-0012 [1978]).

See Brody B. , The Ethics of Biomedical Research: An International Perspective (New York: Oxford University Press, 1998): at 31–54; Goldner J.A. , “An Overview of Legal Controls on Human Experimentation and the Regulatory Implications of Taking Professor Katz Seriously,” St. Louis University Law Journal 38 (1993): 63–134, at 89–103.

Rettig R.A. , “The Industrialization of Clinical Research”, Health Affairs, 19, no. 2 (2000): 129–146, at 130; Kalb P.E. Koehler K.G. , “Legal Issues in Scientific Research,” JAMA 287 (2002): 85–91. See also Oakes J.M. , “Risks and Wrongs in Social Science Research: An Evaluator's Guide to the IRB,” Evaluation Review 26, no. 5 (2002): 443–479, at 451–52; Steinbrook R. , “Protecting Research Subjects — the Crisis at Johns Hopkins,” New Engl. J. Med. 346 (2002): 716–720.

Cases involving FCA claims in the context of research include U.S. ex rel. Chandler v. Hektoen Institute, 35 F. Supp 2d 1078 (N.D. Ill. 1999); U.S. ex rel Chandler v. Hektoen Institute, 118 F. Supp. 2d 902 (N.D. Ill. 2000); United States ex rel. Cantekin v. University of Pittsburgh, 192 F.3d 402 (3d Cir. 1999); US ex rel. Berge v. Univ. of Ala., 104 F.3d 1453 (4th Cir. 1998); and U.S. v. Regents of University of California, 912 F. Supp. 868 (D. Md. 1995). For further discussion see Kalb and Koehler , supra note 7, at 88.

Morin K. , “The Standard of Disclosure in Human Subject Experimentation,” Journal of Legal Medicine 19 (1998): 157–221.

Final Report of the Advisory Committee on Human Radiation Experiments, stock number 061-000-00-848-9 (October 1995); Faden R. , “The Advisory Committee on Human Radiation Experiments: Reflections on a Presidential Commission,” Hastings Center Report 26, no. 5 (1996): 5–10.

Dembner A. , “Lawsuits Target Medical Research,” Boston Globe, August 12, 2002, at A-1, available at <http://www.boston.com/dailyglobe2/138/metro>; Price E.A. and Lemons J.A. , “Clinical Trials: Protecting the Subject, Avoiding Liability, and Managing Risk,” Health Law Digest: Digest Analysis 2002 30, no. 1 (2002): 3–13, at 8–9; Grimes v. Kennedy Krieger, 782 A.2d 807, 838–39 (Md. 2001).

Goldner , supra note 6, at 88.

U. S. v. Stanley, 107 S.Ct. 3054 (1987). LSD, or lysergic acid diethylamide, is an hallucinogenic drug.

Jaffee v. United States, 663 F.2d 1226 (3rd Cir. 1981), cert. denied, 102 S.Ct. 2234 (1982). See also Begay v. United States, 768 F.2d 1059 (9th Cir. 1985); Scott v. Casey, 562 F. Supp. 475 (N.D. Ga. 1983).

Final Report of the Advisory Committee on Human Radiation Experiments, supra note 10.

In re Cincinnati Radiation Litigation, 874 F. Supp. 796 (S.D. Ohio 1995).

Stadt v. University of Rochester, 921 F. Supp. 1023 (W.D.N.Y. 1996). See also Barrett v. United States, 689 F.2d 324 (2d Cir. 1982).

Heinrich v. Sweet, 44 F. Supp. 2d 408 (D. Mass. 1999) (Heinrich I); Heinrich v. Sweet, 49 F. Supp. 2d 27 (D. Mass. 1999) (Heinrich II); Heinrich ex rel. Heinrich v. Sweet, 62 F. Supp. 2d 282 (D. Mass. 1999) (Heinrich III). Interestingly, the First Circuit presents a markedly different description of the facts. Per a jury verdict that found for the defendants on the informed consent issue, the First Circuit describes an effort to bring conscientious science to dying people who were fully informed that it was experimental and risky. Heinrich v. Sweet, 308 F.3d 48 (1st Cir. 2002) (cert. denied June 9, 2003)

Hyman v. Jewish Chronic Disease Hospital, 251 N.Y.S.2d 818 (N.Y. App. 2 Dept 1964); rev'd, Hyman v. Jewish Chronic Disease Hospital, 206 N.E.2d 338 (N.Y. 1965).

Heinrich ex rel. Heinrich v. Sweet, 62 F. Supp. 2d 282 (D. Mass. 1999) (Heinrich III). See also Anderson v. George H. Lanier Memorial Hosp, 982 F.2d 1513 (11th Cir. 1993); Barrett v. United States, 689 F.2d 324 (2d Cir. 1982); Mink v. University of Chicago, 460 F. Supp. 713 (N.D. Ill. 1978); Bibeau v. Pacific Northwest Research Foundation, 980 F. Supp. 349 (D. Or. 1997); Craft v. Vanderbilt Univ., 18 F. Supp. 2d 786 (M.D. Tenn 1998).

In re Cincinnati Radiation Litigation, 874 F. Supp. 796, 807 (S.D. Ohio 1995) (referring to 42 U.S.C. § 1983). See also Barrett v. United States, 689 F.2d 324, 330 (2d Cir. 1982).

Mink v. University of Chicago, 460 F. Supp. 713 (N.D. Ill. 1978).

Karp v. Cooley, 349 F. Supp. 827 (S.D. Tex. 1972), affd, 493 F.2d 408 (5th Cir. 1974).

Burton v. Brooklyn Doctors Hospital, 452 N.Y.S.2d 875 (N.Y. App. Div. 1982).

Burton v. Brooklyn Doctors Hospital, 452 N.Y.S.2d 875 (N.Y. App. Div. 1982). See also Anderson v. George H. Lanier Memorial Hosp, 982 F.2d 1513 (11th Cir. 1993); Friter v. IOLAB Corporation 607 A. 2d 1111 (Pa. Super. 1992); Kus v. Sherman Hospital, 644 N.E.2d 1214 (Ill. App. 2 Dist. 1995) (using experimental intraocular lens implants on poor, uneducated patients).

Moore v. Regents of the University of California, 793 P.2d 479 (Cal. 1990), cert. denied, 112 S. Ct. 2967 (1992).

Grimes v. Kennedy Krieger, 782 A.2d 807 (Md. 2001).

See also Kernke v. The Menninger Clinic Inc., 172 F. Supp. 2d 1347 (D. Kan. 2001); Ande v. Rock, 647 N.W.2d 265, (Wis. App. 2002), cert. denied, 650 N.W.2d 840 (Wis. 2002); cert. denied (sub. nom. Ande v. Fost), 123 S.a. 883 (2003).

The cases include Gelsinger v. Trustees of the University of Pennsylvania; Aderman v. Trustees of the University of Pennsylvania, Robertson v. McGee, Berman v. Fred Hutchinson Cancer Research Center, Wright v. Fred Hutchinson Cancer Research Center, Guckin v. Nagle, Dagosto v. Fred Hutchinson Cancer Research Center, and Lett v. Board of Regents of the Ohio State University. As of October 2002, complaints in these and other cases were available at <www.sskrplaw.com>. See also Price and Lemons , supra note 11, at 8.

Noah , supra note 3, at 370–71.

See Morreim E. H. , “A Dose of Our Own Medicine: CAM, Conventional Medicine, and the Standards of Science,” Journal of Law, Medicine & Ethics 31 (2003): 222–235; Morreim E.H. , “Professionalism and Clinical Autonomy in the Practice of Medicine,” Mt. Sinai Journal of Medicine 69, no. 6 (2002): 370–77.

See Moseley J.B. O'Malley K. Petersen N.J. Menke T. Brody B.A. Kuykendall D.H. Hollingsworth J.C. Ashton C.M. , and Wray N.P. , “A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee,” New Engl. J. Med. 337 (2002): 81–88; Felson D.T. and Buckwalter J. , “Débridement and Lavage for Osteoarthritis of the Knee,” New Engl. J. Med. 347 (2002): 132–133.

See Levine R. , “Clarifying the Concepts of Research Ethics,” Hastings Center Report 9, no. 3 (1979): 21–26, at 22; Noah , supra note 3, at 373, 399–400.

Horng S. and Miller F.G. , “Is Placebo Surgery Unethical?” New Engl. J. Med. 347 (2002): 137–39, at 137; Grunberg S.M. and Cefalu W.T. , “The Integral Role of Clinical Research in Clinical Care,” New Engl. J. Med. 348 (2003): 1386–88, at 1386.

Levine R. , “Clarifying the Concepts of Research Ethics,” Hastings Center Report 9, no. 3 (1979): 21–26; Morin K. , “The Standard of Disclosure in Human Subject Experimentation,” The Journal of Legal Medicine 19 (1998): 157–221, at 166–67.

Goldner , supra note 6, at 114.

Miller F.G. and Rosenstein D.L. , “The Therapeutic Orientation to Clinical Trials,” New Engl. J. Med. 348 (2003): 1383–86, at 1383; Appelbaum P.S. Roth L.H. Lidz C.W. Benson P. , and Winslade W. , “False Hopes and Best Data: Consent to Research and the Therapeutic Misconception,” Hastings Center Report 17, no.2 (1987): 20–24, at 21; Miller F.G. and Brody H. , “A Critique of Clinical Equipoise: Therapeutic Misconception in the Ethics of Clinical Trials,” Hastings Center Report 33, no. 3 (2003): 19–28, at 22; King N.M.P. , “Defining and Describing Benefit Appropriately in Clinical Trials,” Journal of Law, Medicine & Ethics 28 (2000): 332–343, at 339; Katz J. “Human Experimentation and Human Rights”, St. Louis Law Journal 38 (1993): 7–54, at 34; Morin K. “The Standard of Disclosure in Human Subject Experimentation,” The Journal of Legal Medicine 19 (1998): 157–221, at 221; Levine R.J. , Uncertainty in Clinical Research,” Lam, Medicine & Health Care 16 (198): 174–82, at 178.

ECRI, “Should I Enter a Clinical Trial? A Patient Reference Guide for Adults with a Serious or Life-threatening Illness,” (ERCI, February 2002), at 33; Miller and Rosenstein supra note 37, at 1383; Miller and Brody , supra note 37, at 21–22; Churchill L.R. Nelson D.K. Henderson G.E. King N.M.P. Davis A.M. Leahey E. and Wilfond B.S. , “Assessing Benefits in Clinical Research: Why Diversity in Benefit Assessment Can be Risky,” IRB: Ethics & Human Research 25, no. 3 (2003): 1–8, at 3. But see Peppercorn J.M. Weeks J.C. Cook E.F. and Joffe S. , “Comparison of Outcomes in Cancer Patients Treated Within and Outside Clinical Trials: Conceptual Framework and Structured Review,” Lancet 363 (2004): 263–70

Abate T. , “Rules for Clinical Trials are Confusing, Inconsistent: No Single Agency Regulates Medical Research on Humans, Putting Millions of Volunteers at Risk,” San Francisco Chronicle, August 5, 2002, at A-1, available at <http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2002/08/05/MN47420.DTL>.

See Appelbaum P.S. Lidz C.W. , and Meisel A. , Informed Consent: Legal Theory and Clinical Practice (New York: Oxford University Press, 1987), at 237–240; Appelbaum , supra note 37, at 20–21; Appelbaum P.S. Roth L.H. , and Lidz C. , “The Therapeutic Misconception: Informed Consent in Psychiatric Research,” International Journal of Law & Psychiatry 5, no. 3-4 (1982): 319–29, at 320–21; Fried C. , Medical Experimentation: Personal Integrity and Social Policy (New York: American Elsevier Publishing Col, Inc., 1974), at 47–56.

Nozick R. , Anarchy, State, and Utopia (New York: Basic Books, Inc., 1974), at 29, 32.

As noted by Miller and Brody , this view contrasts with an alternative in which the researcher is thought to owe his patient the best available treatment. Miller and Brody , supra note 37.

Goldner , supra note 6, at 72.

Fortner v. Koch, 261 N.W. 762, 765 (Mich. 1935).

Moore v. Regents of the University of California, 793 P.2d 479 (Cal. 1990), cert. denied 112 S. Ct. 2967 (1992).

Id., at 481. See also Moore v. Regents of the University of California, 249 Cal. Rptr. 494, 500 (Cal. App. 2 Dist. 1988).

Almost none of the various tissues Golde harvested from Moore could even be used to monitor his wellbeing, because “remissions in the splenectomy series are defined solely by improvement in peripheral blood cytopenias.” Id. at 2005

“Moore, at one point, mentioned that he could not afford to continue to travel to Los Angeles and suggested that he obtain his continuing care in Seattle. In response, Golde told Moore that he would obtain grant funds to pay for Moore's trips. Later, when Moore expressed concern about the cost of accommodations, Golde offered to pay Moore's expenses at a ‘luxurious hotel in Beverly Hills.’ On the first trip thereafter, Golde presented Moore with a Very elaborate and very complicated' consent form purporting to ‘give away the rights to [the] cell line and products derived therefrom.’ Unaware of Guide's development efforts, Moore signed the form giving his consent. On his next and last visit, Golde again asked Moore to sign a form. Moore, believing that Dr. Golde's answers to his questions were Vague and…quite patronizing,' signed the form explicitly withholding his consent by circling a box marked ‘I do not consent.’ Moore became suspicious and contacted an attorney as Golde repeatedly tried to persuade Moore to sign the form ‘in the correct fashion.’ Moore subsequently filed suit against the Regents, as patent holders, and against Golde and his research assistant.” Id. at 130–31.

A federal court recently defined medical treatment as “actions…taken in an effort to benefit or cure the patient.” Craft v. Vanderbilt Univ., 18 F. Supp. 2d 786,796 (M.D. Tenn 1998); see also Payette v. Rockefeller University, 643 N.Y.S.2d 79 (App Div 1 Dept. 1996).

Bergman , supra note 48, at 127–45

Kernke v. The Menninger Clinic Inc., 172 F. Supp. 2d 1347 (D. Kan. 2001).

Id. at 1354; See also Heinrich ex rel. Heinrich v. Sweet, 62 F. Supp. 2d 282, 313 (D. Mass. 1999).

Payette v. Rockefeller University, 643 N.Y.S.2d 79 (App Div 1 Dept. 1996).

Arguably, courts that equate research with ordinary practice labor under their own “therapeutic misconception,” an assumption that somehow research, simply because it involves medical interventions, must be geared toward providing direct benefit for each patient, and that therefore the proper standard for assessing research interventions must be the same as for standard medical care. See Appelbaum , supra note 37; Appelbaum Roth , and Lidz , supra note 40.

Miller and Brody discuss in detail the conceptual and ethical problems inherent in seeing research as a form of therapeutic enterprise. Miller and Brody , supra note 37.

In Dahl v. HEM Pharmaceuticals Corp. , 7 F.3d 1399, 1404 (9th Cir. 1993), research participants sued to receive the year's worth of drug they had been promised in exchange for participating in a study of chronic fatigue syndrome. The court found that a contract existed, and the participants were owed the drug in exchange for their contribution to the research. These patients had “submitted themselves to months of periodic injections with an experimental drug, or unbeknownst to them, mere saline solution, combined with intrusive and necessarily uncomfortable testing…HEM sought to have them participate in its study so that it could obtain FDA approval for its new drug,” and so the company was obligated to keep its end of the bargain.

See also Barrett v. United States, 689 F.2d 324 (2d Cir. 1982); In re Cincinnati Radiation Litigation, 874 F. Supp. 796, 814 (S.D.Ohio 1995); Anderson v. George H. Lanier Memorial Hosp., 982 F.2d 1513, 1519 (11th Cir. 1993).

McCoid A.H. , “The Care Required of Medical Practitioners,” Vanderbilt Law Review 12 (1959): 549–632, at 565.

Peters P.G. , “The Quiet Demise of Deference to Custom: Malpractice Law at the Millennium,” Washington and Lee Law Review 57 (2000): 163–205.

45 C.F.R. § 46.111; Horng and Miller , supra note 34, at 137. See also Emanuel E.J. Wendler D. , and Grady C. , “What Makes Clinical Research Ethical?” JAMA 283 (2000): 2701–11 (discussing seven criteria for ethical research: [1] value; [2] scientific validity; [3] fair subject selection; [4] favorable risk-benefit ratio; [5] independent review; [6] informed consent; and [7] respect for enrolled subjects).

Kernke v. The Menninger Clinic Inc., 172 F. Supp. 2d 1347 (D.Kan. 2001).

Burton v. Brooklyn Doctors Hospital, 452 N.Y.S.2d 875 (N.Y. App. Div. 1982).

Ellenberg S.S. Fleming T.R. , and Demets D.L. , Data Monitoring Committees in Clinical Trials: A Practical Perspective (Hoboken: John Wiley & Sons, 2002).

Unlike research, innovation is not subject to regulation. For instance, the FDA refrains from governing off-label prescribing, a common form of innovation. See Noah , supra note 3, at 398. See also Southard v. Temple Univ. Hosp., 781 A.2d 101, 104 (Pa. 2001); Blazoski v. Cook, 787 A.2d 910, 919 (N.J. Super. A.D. 2002).

IRBs must ensure, for example, that risks to subjects are minimized; risks are reasonable relative to anticipated benefits; selection of subjects is equitable; informed consent is sought from each subject or legally authorized representative; informed consent is appropriately documented; data are appropriately monitored to ensure subjects' safety; subjects' privacy is appropriately protected; and vulnerable populations such as children and the mentally disabled are provided added levels of protection. 45 C.F.R. § 46.111

Currently, federal regulations apply to research that receives federal funding, and to the entire spectrum of research in academic institutions that receive federal funding via “multiple project assurances.” Companies using their own funds to sponsor trials for FDA approval must conform to FDA rules, which still require IRB surveillance. However, some research escapes supervision altogether. For instance, since the FDA does not require approval of new surgical procedures, or of off-label uses of drugs and devices (unless the manufacturer wants to change its labeling), research in these areas can escape supervision if it does not involve federal funding and is not undertaken at an institution that has assured the government it will supervise all research within its walls. See generally Rettig R.A. , “The Industrialization of Clinical Research,” Health Affairs 19, no. 2 (2000): 129–46, at 139; Kalb P.E. and Koehler K.G. “Legal Issues in Scientific Research,” JAMA 287 (2002): 85–91, at 87; Price E.A. and Lemons J.A. , “Clinical Trials: Protecting the Subject, Avoiding Liability, and Managing Risk,” Health Law Digest: Digest Analysis 30, no. 1 (2002): 3–13, at 6.

Helling v. Carey, 519 P.2d 981 (Wash, 1974); Hooper T.J. , 60 F.2d 737 (2d. Cir. 1932).

Generally a fiduciary relationship is one in which “trust and confidence are reposed by one party in the influence or dominance of another, creating in the latter a duty to act with greater diligence and care than that required by a common negligence standard of due care.” Curran W.J. and Moseley G.B. , “The Malpractice Experience of Health Maintenance Organizations,” Northwestern University Law Review 70 (1975): 69–89, at 76. See also Shepherd J.C. , The Law of Fiduciaries (Toronto: Carswell Company Ltd, 1981); DeMott D.A. , “Beyond Metaphor: An Analysis of Fiduciary Obligation,” Duke Law Journal 819 (1988): 879–924; Frankel T. , “Fiduciary Law,” California Law Review 71 (1983): 795–836.

Rodwin M.A. , “Conflicts in Managed Care,” New Engl. J. Med. 332 (1995): 605–07; Rodwin M.A. , Medicine Money & Morals: Phyisicians' Conflicts of Interest (New York: Oxford University Press, 1993).

See, e.g., D.A.B. v. Brown, 570 N.W.2d 168 (Minn. App. 1997); Spoor v. Serota, 852 P.2d 1292 (Colo. App. 1992); Awai v. Kotin, 872 P.2d 1332 (Colo. App. 1993).

McCloud v. Seier, 567 SW2d 127 (Mo. 1978); Garcia v. Coffman, 946 P.2d 216 (N.M. App. 1997); Lockert v. Goodill, 430 P.2d 587 (Wash. 1967); Miller v. Kennedy, 522 P.2d 852, 860–61 (Wash. Ct. App. 1974), aff'd, 530 P.2d 334 (Wash. 1975); Hammonds v. Aetna Cas. & Sur. Co., 243 F. Supp. 793, 801–01 (N.D. Ohio 1965); Murphy v. Godwin, 303 A.2d 668 (Del. Super. 1973); Shadrick v. Coker, 963 S.W.2d 726 (Tenn. 1998); Sard v. Hardy, 379 A.2d 1014 (Md. App. 1977); Roy v. Hartogs, 366 N.Y. S. 2d 297 (N.Y. 1975); Gates v. Jensen, 595 P.2d 919 (Wash. 1979); Bowman v. McPheeters, 176 P.2d 745, 748 (Cal. 1947); Natanson v. Kline, 350 P.2d 1093, 1101, 1103 (Kan. 1960); Berkey v. Anderson, 82 Cal. Rptr. 67, 77–78 (Cal. App. 2 Dist. 1969); Tighe v. Ginsberg, 540 NYS 2d 99 (1989); Mac-Donald v. Clinger, 446 NYS 2d 801 (1982); Wohlgemuth v. Meyer, 293 P.2d 816 (Cal. App. 1 Dist. 1956); Moore v. Regents of the Univ. of Cal., 793 P.2d 479, 483 (Cal. 1990); Petrillo v. Syntex Laboratories, Inc., 499 N.E.2d 952 (Ill. App. 1 Dist. 1986); Lownsbury v. VanBuren, 762 N.E.2d 354 (Ohio 2002).

“The United States Supreme Court has noted that the central purpose of fiduciary law is to govern the exercise of discretion in making decisions that are not, and cannot be, controlled in advance by legal means.” Jacobson P.D. and Cahill M.T. , “Applying Fiduciary Responsibilities in the Managed Care Context,” American Journal of Law & Medicine 26 (2000): 155–73, at 160.

That is, a fiduciary relationship does not arise simply because one person needs or chooses to trust another, but because the latter agrees to this distinctive kind of arrangement. “We have said that ‘[f]iduciary duty is not created by a unilateral decision to repose trust and confidence; it derives from the conduct or undertaking of the purported fiduciary’ and have defined a fiduciary as ‘[a] person having duty, created by his own undertaking, to act primarily for another's benefit in matters connected with such undertaking.’” Long v. Great West Life & Annuity Ins., 957 P.2d 823, 829 (Wyo. 1998). See also Johnson v. Brewer & Pritchard, P.C., 73 S.W.3d 193, 200 (Tex. 2002), citing Restatement 2d. of Agency § 13, cmt. a(1958); Greenberg v. Miami Children's Hospital Research Institute, 264 F. Supp. 2d 1064 (S.D. Fla 2003).

The fiduciary “is held to something stricter than the morals of the market place. Not honesty alone, but the punctilio of an honor the most sensitive, is then the standard of behavior;” the fiduciary's conduct must be “kept at a level higher than that trodden by the crowd.” Meinhard v. Salmon, 164 N.E. 545, 546 (NY 1928).

Physicians in ordinary practice cannot completely avoid conflicts of interest or of obligation. Various forms of payment bring potential conflict, for instance, whether fee-for-service (with an incentive to provide needless services) or capitation (with incentive to withhold helpful but costly services). Nevertheless, the physician must still focus on the patient's interest.

Holder A.R. , “Do Researchers and Subjects Have a Fiduciary Relationship?” IRB 4, no.1 (1982): 6–7, at 6. Karin Morin also suggests that traditionally the physician-patient relationship and the investigator-subject relationship have both been described as fiduciary. Morin K. , “The Standard of Disclosure in Human Subject Experimentation,” Journal of Legal Medicine 19 (1998): 157–221, at 216. See also Vodopest v. MacGregor, 913 P.2d 779, 788 (Wash. 1996).

Even the leading case emphasizing investigators” duties toward subjects does not deem the relationship fiduciary, but rather a “special relationship.” Grimes v. Kennedy Krieger, 782 A2d 834, 843 (Md. 2001).

Klein and Fleischman , supra note 4. See also Kass J.E. Sugarman J. Faden R. , and Schoch-Spana M. , “Trust: The Fragile Foundation of Contemporary Biomedical Research,” Hastings Center Report 26, no. 5 (1996): 25–29, at 27; Penman D. , “Informed Consent for Investigational Chemotherapy: Patients' and Physicians' Perceptions,” Journal of Clinical Oncology 2 no. 7 (1984): 849–55; Rajagopal S. Goodman P.J. , and Tannock I.F. , “Adjutant Chemotherapy for Breast Cancer: Discordance Between Physicians” Perception of Benefit and the Results of Clinical Trials,” Journal of Clinical Oncology 12, no. 6 (1994): 1296–1304.

Moore v. Regents of the University of California, 793 P.2d 479 (Cal. 1990), cert. denied 112 S. Ct. 2967 (1992).

The California Supreme Court affirmed breach of fiduciary duty as a valid cause of action in this case. Id. at 483, 485. See also McCall v. Pacificare of Cal., Inc., 21 P.3d 1189 (Cal. 2001).

“While investigators also unequivocally have an obligation to minimize harm to subjects and to respect their wishes, patients who enroll as research subjects must understand this shift in loyalties that is inherent to the role of investigators, in contrast to that of patients' personal physicians.” Kass , supra note 75, at 28; Katz , supra note 37, at 34; Goldner , supra note 6, at 122.

Appelbaum , supra note 37, at 23. Similarly, independent consent or procedure monitors have been proposed. Klein and Fleischman supra note 4, at 25.

The National Institutes of Health now requires what it calls “Research Subject Advocates” to be involved in all trials funded through its General Clinical Research Centers. See National Center for Research Resources, Guidelines for the General Clinical Research Centers Program (November 2001), available at <http://www.ncrr.nih.gov/clinical/crguide2001/guide-nov2001.pdf>, at 11. See also Morreim E.H. , “By Any Other Name: The Many Iterations of ‘Patient Advocate’ in Clinical Research,” IRB: Ethics & Human Research (2004), forthcoming.

“The law of battery also protects against touchings that are offensive, even if they do not inflict bodily harm. In so doing, battery protects ‘the purely dignitary interest in the body that it be free from offensive contact.’” Meisel A. “A “Dignitary Tort” as a Bridge Between the Idea of Informed Consent and the Law of Informed Consent,” Law, Medicine & Health Care 16 (1988): 210–18, at 211. See also Friter v. IOLAB Corporation, 607 A2d 1111, 1115 (Pa. Super. 1992); Mink v. University of Chicago, 460 F. Supp. 713, 718 (N.D. Ill. 1978), citing Restatement 2d. of Torts; Cardwell v. Bechtol, 724 S.W.2d 739, 750 (Tenn. 1987).

Mohr v. Williams, 104 N.W. 12 (1905); Rolater v. Strain, 137 P. 96 (Okla. 1913); Schloendorff v. Society of New York Hospital, 105 N.E. 92 (N.Y. 1914).

Natanson v. Kline, 350 P.2d 1093 (Kan. 1960); Natanson v. Kline, 354 P.2d 670 (Kan. 1960); Cobbs v. Grant, 502 P.2d 1 (1972); Canterbury v. Spence, 464 F.2d 772 (D.C. 1972); Wilkinson v. Vesey, 295 A.2d 676 (R.I. 1972); Cobbs v. Grant, 502 P.2d 1, 8 (1972). See also Meisel , supra note 81, at 211; Morin K. , “The Standard of Disclosure in Human Subject Experimentation,” The Journal of Legal Medicine 19 (1998): 157–221, at 160ff.; supra note 3, at 364 ff; Krause J.H. , “Reconceptualizing Informed Consent in an Era of Health Care Cost Containment,” Iowa Law Review 85 (1999): 261–386, at 270–72; Goldner , supra note 6, at 74–78; Mink v. University of Chicago, 460 F. Supp. 713, 716–17 (N.D. Ill. 1978).

Trogun v. Fruchtman, 207 N.W.2d 297, 313 (Wis. 1973).

Perry v. Shaw, 106 Cal.Rptr.2d 70, 73 (Cal. App.2 Dist. 2001). See also Howard v. University of Medicine, 800 A.2d 73, 80 (N.J. 2002); Trogun v. Fruchtman, 207N.W.2d 297, 313 (Wis. 1973); Shultz M.M. , “From Informed Consent to Patient Choice: A New Protected Interest,” Yale Law Journal 95 (1985): 219–99, at 225.

Grabowski v. Quigley, 684 A.2d 610, 615 (Pa. Super. 1996)

Gouse v. Cassel, 615 A.2d 331, 333 (Pa. 1992); Grabowski v. Quigley, 684 A.2d 610 (Pa. Super. 1996); Duttry v. Patterson, 741 A.2d 199, 203 (Pa. Super 1999); Taylor v. Albert Einstein Medical Center, 723 A.2d 1027, 1035 (Pa. Super. 1998); Krause , supra note 83, at 309.

Heinrich v. Sweet, 49 F. Supp. 2d 27, 38 (D. Mass. 1999) (Heinrich II).

Some states, such as Pennsylvania and Tennessee, still emphasize battery as the cornerstone of the duty to disclose. See Morgan v. MacPhail, 704 A.2d 617, 620 (Pa. 1997); Duttry v. Lewis T. Patterson, M.D., 771 A.2d 1255 (Pa. 2001); Cardwell v. Bechtol, 724 S.W.2d 739 (Tenn. 1987); Shadrick v. Coker, 963 S.W.2d 726 (Tenn. 1998).

Mink v. University of Chicago, 460 F. Supp. 713 (N.D. Ill. 1978) citing Cathemer v. Hunter, 558 P.2d 975, 978 (1976). See also Perry v. Shaw, 106 Cal.Rptr.2d 70 (Cal. App.2 Dist. 2001); Curtis v. Jaskey, 759 N.E.2d 962 (Ill. App. 2 Dist. 2001); Lloyd v. Kull, 329 F.2d 168 (7th Cir. 1964); Harvey v. Strickland, 566 S.E.2d 529 (S.C. 2002); Lojuk v. Quandt, 706 F.2d 1456 (7th Cir. 1983), cert. denied, 106 S.Ct. 822 (1986); Gragg v. Calandra, 696 N.E.2d 1282 (Ill. App. 2 Dist. 1998); Roberson v. Provident House, 576 So.2d 992 (La. 1991).

Karl. J. Pizzalotto, M.D., Ltd. v. Wilson, 437 So.2d 859 (La. 1983).

Similarly, in Russell v. Murphy , the patient expressly wanted local anesthesia but instead received general anesthesia. Russell v. Murphy, 86 S.W.3d 745 (Tex.App. 2002). See also Cobbs v. Grant, 502 P.2d 1, 7 (Cal. 1972); Gaskin v. Goldwasser, 520 N.E. 1085, 1094 (Ill.App. 4 Dist. 1988); Cathemer v. Hunter, 558 P.2d975 (Ariz. App. 1976); Benton v. Snyder, 825 S.W.2d 409 (Tenn. 1992); Perin v. Hayne, 210 N.W.2d 609 (Iowa 1973); Hernandez v. Schittek, 713 N.E.2d 203 (Ill. App. 3 Dist. 1999); Schloendorff v. Society of New York Hospital, 105 N.E. 92 (N.Y. 1914).

In some instances courts have been willing to see a physician's misrepresentation of his credentials or experience as an instance of battery. See Hales v. Pittman, 576 P.2d 493 (Ariz. 1973); Guebard v. Jabay, 452 N.E.2d 751 (Ill. App. 2 Dist. 1983); Duttry v. Patterson, 741 A.2d 199 (Pa. Super 1999); reversed, Duttry v. Lewis T. Patterson, M.D., 771 A.2d 1255 [Pa. 2001]). But see Howard v. University of Medicine, 800 A.2d 73 (N.J. 2002); Taylor v. Johnston, 985 P.2d 460 (Alaska 1999).

Note that this modified battery tort would not apply to clinical innovation, which, as noted above, still focuses on the best interests of the individual. Innovation may feature significant uncertainty, and a number of courts have held that physicians should inform patients when an intervention is untested. See, e.g., Gaston v. Hunter, 588 P.2d 326, 351 (Ariz. App. 1978); Ahern v. Veterans Administration, 537 F.2d 1098, 1102 (10th Cir. 1976); Estrada v. Jaques, 321 S.E.2d 240 (N.C. App. 1984); Retkwa v. Orentreich, 584 N.Y.S.2d 710 (Sup. 1992); Corrigan v. Methodist Hosp., 874 F. Supp. 657 (E.D. Pa. 1995); Shadrick v. Coker, 963 S.W.2d 726 (Tenn. 1998); Salgo v. Leland Stanford Jr. University Bd. of Trust., 317 P.2d 170, 179–80 (Cal. 1957). But see Southard v. Temple Univ. Hosp., 781 A.2d 101, 104 (Pa. 2001); Blazoski v. Cook, 787 A.2d 910, 919 (N.J. Super. A.D. 2002). See also Noah , supra note 3, at 372.

Noah , supra note 3, at 398; Southard v. Temple Univ. Hosp., 781 A.2d 101, 104 (Pa. 2001); Blazoski v. Cook, 787 A.2d 910, 919 (N.J. Super. A.D. 2002).

45 C.F.R. § 46.101(b)(4).

In 2003, for instance, the National Naval Medical Center suspended all orthopedic and radiology research after discovering that a study of shoulder injuries had not been submitted for IRB approval. See Altaian L.K. , “Naval Center Halts Research During Inquiry About Ethics”, New York Times, September 28, 2003, available at <http://www.nytimes.com/2003/09/28/national/28ETHI.html>.

Krause , supra note 83, at 314; Noah , supra note 3, at 367.

Canterbury v. Spence, 464 F.2d 772 (D.C. 1972); Cobbs v. Grant, 502 P.2d 1 (1972); Wilkinson v. Vesey, 295 A.2d 676 (R.I. 1972).

Not all states use this objective standard. See, e.g., Scott v. Bradford, 606 P.2d 554 (Okl. 1980). For further discussion see Morris G.H. , “Dissing Disclosure: Just What the Doctor Ordered,” Arizona Law Review 44 (2002): 313–71, at 331 ff.

U.S. Department of Health, Education, and Welfare, National Commission for the Protection of Human Subjects of Biomedical and behavioral Research, The Belmont Report: Ethical Principles and Guidelines/or the Protection of Human Subjects of Research (Pub. No. (OS) 78-0012) (1978), reprinted in Brody B. , The Ethics of Biomedical Research (New York: Oxford University Press, 1998), at 285.

45 C.F.R. § 46.116. See also Bein P.M. , “Surrogate Consent and the Incompetent Experimental Subject,” Food Drug Cosmetic Law Journal 46 (1991): 739–71, at 743; Grimes v. Kennedy Krieger, 782 A.2d 807, 849 (Md. 2001).

See, e.g., Anderson v. George H. Lanier Memorial Hosp, 982 F.2d 1513 (11th Cir. 1993); Mink v. University of Chicago, 460 F. Supp. 713 (N.D. Ill. 1978); Perna v. Pirozzi, 457A.2d431 (N.J. 1983).

Jurisdictions differ markedly on threshold questions such as whether a physical injury or the threat of one is required. See Molien v. Kaiser Foundations Hospitals, 616 P.2d 813 (Cal. 1980); Rowe v. Bennett, 514 A.2d 802 (Me. 1986); Willis v. Ashby, 801 A.2d 442 (N.J. Super. A.D. 2002); Perry-Rogers v. Obasaju, 723 N.Y.S.2d 28,29 (A.D. 1 Dept. 2001); Perna v. Pirozzi, 457 A.2d 431,438 (N.J. 1983); Martell v. St. Charles Hosp., 523 N.Y.S.2d 342 (Sup. 1987); Hecht v. Kaplan, 645 N.Y.S.2d 51 (A.D. 2 Dept. 1996).

Moore v. Regents of the University of California, 793 P.2d 479 (Cal. 1990), cert. denied 112 S. Ct. 2967 (1992).

See White v. Paulsen, 997 F. Supp. 1380 (E.D. Wash. 1998); In re. Cincinnati Radiation Litigation, 874 F. Supp. 796 (S.D. Ohio 1995); Blanton v. United States, 428 F. Supp. 360 (D.D.C. 1977); Lugenbuhl v. Dowling, 701 So.2d447 (La. 1997).

See, e.g., Perna v. Pirozzi, 457 A.2d 431, 438 (N.J. 1983); Gragg v. Calandra, 696 N.E.2d 1282 (Ill. App. 2 Dist. 1998). But see Brzoska v. Olson, 668 A.2d 1355 (Del. 1995). For further discussion see Levit N. Torts Ethereal ,” George Washington Law Review 61 (1992): 136–92, at 142–46, 170–72.

Berman v. Allan, 404 2d. 8 (N.J. 1979).

Berman , 404 2d. at 14. See also, e.g., Lodato ex rel. v. Kappy, 803 A.2d 160, 166 (N.J. Super. A.D. 2002).

Shultz , supra note 86; Meisel , supra note 81; Levit , supra note 109; Morris , supra note 100; Krause , supra note 83; Weisbard A.J. , “Informed Consent: The Law's Uneasy Compromise with Ethical Theory,” Nebraska Law Review 65 (1986): 749–67; Goldstein J. , “For Harold Lasswell: Some Reflections on Human Dignity, Entrapment, Informed Consent, and the Plea Bargain,” Yale Law Journal 84 (1975): 683–703, at 691.

Some observers would like to press dignity torts even further. During the late 1990s and early 2000s a series of lawsuits against several major research institutions attempted to bring dignity torts into the research arena by arguing that the Nuremburg Code and the Declaration of Helsinki warrant a dignity tort when research subjects are inadequately informed about the protocol's objectives and risks. As of August 2003, for instance, the website http://www.sskrplaw.com featured several cases arguing for such causes of action.

Courts have not been receptive to importing international ethics codes into U.S. law. Just one court has indicated any willingness to regard the Nuremberg Code or the Declaration as U.S. law. The Maryland Court of Appeals, arguing that there is a special relationship between investigator and subject, acknowledged that although no United States court “has ever awarded damages to an injured experimental subject, or punished an experimenter, on the basis of a violation of the Nuremberg Code,” nevertheless the Code was intended for international application and has never been rejected in the U.S. Grimes v. Kennedy Krieger, 782 A.2d 807, 834 (Md. 2001). Even here, the court's interest in the Code appears as dicta rather than black-letter law.

Several other courts have cited the Nuremberg Code and Helsinki Accords, but as ideals, not as domestic law. See, e.g., In re Cincinnati Radiation Litigation, 874 F. Supp. 796, 821–22 (S.D. Ohio 1995). See also Heinrich ex rel. Heinrich v. Sweet, 62 F. Supp. 2d 282, 321 (D. Mass. 1999) (Heinrich III); Whitlock v. Duke University, 637 F. Supp. 1463, 1470–71 (M.D.N.C. 1986), aff'd, 829 F.2d 1340 (4th Cir. 1987); U. S. v. Stanley, 107 S.Ct. 3054, 3065 (O'Conner, J. dissenting), 3066 (Brennan, J. dissenting) (1987); White v. Paulsen, 997 F. Supp. 1380, 1383–84 (E.D. Wash. 1998); Hoover v. West Virginia Dept of Health and Human Services, 984 F. Supp. 978, 978 (S.D. W. Va. 1997), aff'd, 129 F.3d 1259 (11th Cir. 1997).

Heinrich v. Sweet, 308 F.3d 48,60–61 (1st Cir. 2002) (Heinrich VI).

Lugenbuhl v. Dowling, 701 So.2d 447, 455–56 (La. 1997).

In Diaz v. Tampa General Hospital , such reasoning led to a high-dollar settlement in a case where no physical injury was ever claimed. Plaintiffs' argument was that sophisticated consent forms were tantamount to inadequate research disclosures for pregnant women whose socioeconomic and cultural status impeded their comprehending the information they were given. Plaintiffs were poor, uneducated, mostly Spanish-speaking women who said that they did not understand the three-page, IRB-approved consent form. In addition to conceding there was no injury, the plaintiffs also agreed that they had signed the consent form. When the case was certified as a class action, defendants determined they could not afford to defend the suit. A settlement of $3.8 million closed the case. Diaz v. Tampa General Hospital, 2000 WL1682918 (M.D. Fla. 2000). See also Research “Roundtable Report on Diaz v. Tampa General,” at <www.researchround-table.com>.

Krause , supra note 83, at 366.

Canterbury v. Spence, 464 F.2d 772, 791 (D.C. 1972). See also Lugenbuhl v. Dowling, 701 So.2d 447, 454 (La. 1997); Sard v. Hardy, 379 A.2d 1014, 1025 (Md. App. 1977); Guebard v. Jabay, 452 N.E.2d 751, 757 (Ill. App. 2 Dist. 1983); Howard v. University of Medicine, 800 A.2d 73, 79, 84 (N.J. 2002); Krause , supra note 83 at 317

Woolley v. Henderson 418 A.2d 1123, 1132 (Me. 1980); Sard v. Hardy, 379 A.2d at 1025; Canterbury v. Spence, 464 F.2d 772, 790–91 (D.C. 1972); Arena v. Gingrich, 748 P.2d 547, 549 (Or. 1988).

Schreiber v. Physicians Ins. Co., 588 N.W.2d 26, 34 (Wis. 1999).

See Krause , supra note 83, at 319; Weisbard , supra note 112', at 760.

Katz , supra note 38, at 25.

Zalazar v. Vercimak, 633 N.E.2d 1223 (Ill. App. 3 Dist. 1993).

Zalazar v. Vercimak, 633 N.E.2d 1226.

Schreiber v. Physicians Ins. Co. , 588 N.W.2d 26 (Wis. 1999).

Id. at 34.

“This basic right to know and decide is the reason for the full-disclosure rule… Although it might be said this approach places a physician at the mercy of a patient's hindsight, a careful practitioner can always protect himself by insuring that he has adequately informed each patient he treats.” Scott v. Bradford, 606 P.2d 554, 559 (Okla. 1980). See also Zalazar v. Vercimak, 633 N.E.2d 1223, 1227 (Ill. App. 3 Dist. 1993); Noah , supra note 3, at 369.