1 See Dan Vergano, Drug-Trial Deaths “Go Unreported”, USA TODAY, Nov. 8, 2000, at 12D; see also Tom Abate, Maybe Conflicts of Interest Are Scaring Clinical Trial Patients, S.F. CHRON., Apr. 30, 2001, at D1 (reporting an increase from 502,000 in 1995 to 700,000 in 1999); Philip J. Hilts, In Tests on People, Who Watches the Watchers?, N.Y. TIMES, May 25, 1999, at F1 (“[T]he General Accounting Office has estimated that 16,000 to 20,000 experiments on an unknown number of people are conducted in the United States each year. And the number and complexity of studies, which might involve thousands of patients, appear to be rising sharply.”); Wendy K. Mariner, Human Subjects, NAT’L L.J., May 13, 2002, at A25 (“Billions of dollars are spent annually on research that uses human subjects.”).

2 See Naomi Aoki, Lack of Human Test Subjects a Bitter Pill for Drug Makers, BOSTON GLOBE, Oct. 11, 2000, at D4; Ulysses Torassa, Putting Trials to the Test: After Asthma Study Death, Volunteers Weigh Risks, Benefits of Participating, S.F. CHRON., July 29, 2001, at B3; Dan Vergano, Drug Trials Vex Medical Ethics: Academic Experts Put Testing by Private Companies Under a Microscope, USA TODAY, Aug. 8, 2000, at 9D; see also Berkwits, Michael, Clinical Trial Acronyms and the “Branding” of Clinical Research, 133 ANNALS INTERNAL MED. 755, 757-59 (2000)CrossRefGoogle ScholarPubMed (criticizing the naming of clinical trials with memorable acronyms (e.g., GUSTO) as a subtle form of advertising that may mislead researchers and subjects about the effectiveness of the investigational treatment).

3 See Kurt Eichenwald & Gina Kolata, Drug Trials Hide Conflicts for Doctors, N.Y. TIMES, May 16, 1999, § 1, at 1; Kurt Eichenwald & Gina Kolata, A Doctor's Drug Trials Turn into Fraud, N.Y. TIMES, May 17, 1999, at A1 (“[T]he industry has turned to thousands of private-practice doctors, for whom testing drugs has become a sideline for making money.”); Rachel Zimmerman, Desperately Seeking Kids for Clinical Trials, WALL ST. J., May 29, 2002, at D1; see also OFFICE OF INSPECTOR GENERAL, HHS, RECRUITING HUMAN SUBJECTS: PRESSURES IN INDUSTRY-SPONSORED CLINICAL RESEARCH, OEI-01-97-00195, at 16-20 (2000), available at http://www.researchroundtable.com/pdfiles/a459.pdf.

4 See Ceci Connolly, Price Tag for a New Drug, WASH. POST, Dec. 1, 2001, at A10 (reporting estimates that place the average investment for an approved new drug at more than $800 million, and adding that the figure had more than tripled in the space of a decade, largely because of demands for larger and more complex clinical trials).

5 See Gina Kolata & Kurt Eichenwald, For the Uninsured, Drug Trials Are Health Care, N.Y. TIMES, June 22, 1999, at A1.

6 See Food and Drug Administration Modernization Act, Pub. L. No. 105-115, § 113, 111 Stat. 2296 (1997); see also David Brown, Medicare to Pay for Experimental Treatments: Clinton Aims to Bring More Seniors into Clinical Trials, WASH. POST, June 8, 2000, at A9 (describing another federal initiative designed to facilitate access to trials). One decade earlier Congress had directed the agency to establish a similar registry of clinical trials of investigational AIDS drugs. See AIDS Amendments of 1988, Pub. L. No. 100-607, § 201, 102 Stat. 3048, 3062, 3072 (codified as amended at 42 U.S.C. § 300cc-17(d)&(e) (2000)). The NIH's clinical trials database can be found at http://clinicaltrials.gov.

7 See, e.g., Schuck, Peter H., Rethinking Informed Consent, 103 YALE L.J. 899, 902 n.15 (1991)CrossRefGoogle Scholar (“This Article is concerned with informed consent in treatment decisions, not in clinical research settings.”). For one notable, though now somewhat dated, exception, see Alexander Morgan Capron, Informed Consent in Catastrophic Disease Research and Treatment, 123 U. PA. L. REV. 340, 362-63 (1974). For more recent overviews of these issues, see JESSICA W. BERG ET AL., INFORMED CONSENT: LEGAL THEORY AND CLINICAL PRACTICE 249-303 (2d ed. 2001); id. at 253 (noting “the distinct and often disparate development of the regulation of consent to research versus development of the law relating to consent to treatment”); Morin, Karine, The Standard of Disclosure in Human Subject Experimentation, 19 J. LEGAL MED. 157 (1998)CrossRefGoogle ScholarPubMed; Symposium, Legal and Ethical Controls on Biomedical Research: Seeking Consent, Avoiding Condescension, 38 ST. LOUIS U. L.J. 3 (1993)Google Scholar. The extensive scholarly work of Dr. Jay Katz, which is cited throughout this Article where relevant, represents the most significant exception to this tendency to marginalize issues of experimentation when discussing the informed consent doctrine. Conversely, Professor George Annas has written extensively about human experimentation, addressing among other issues the special role of informed consent in that setting.

8 See, e.g., Pratt v. Davis, 79 N.E. 562, 564-65 (Ill. 1906); Rolater v. Strain, 137 P. 96, 97-99 (Okla. 1913); Mendelson, Danuta, Historical Evolution and Modern Implications of Concepts of Consent to, and Refusal of, Medical Treatment in the Law of Trespass, 17 J. LEGAL MED. 1, 29-35 (1996)CrossRefGoogle ScholarPubMed; see also Sard v. Hardy, 379 A.2d 1014, 1019 (Md. 1977) (referring to “the universally recognized rule that a physician, treating a mentally competent adult under non-emergency circumstances, cannot properly undertake to perform surgery or administer other therapy without the prior consent of his patient”).

9 See Natanson v. Kline, 350 P.2d 1093, 1100-07 (Kan. 1960), clarified, 354 P.2d 670 (Kan. 1960); Kohoutek v. Hafner, 383 N.W.2d 295, 298-300 (Minn. 1986); Baird v. American Med. Optics, 713 A.2d 1019, 1027-28 (N.J. 1998); cf. Meisel, Alan, The Expansion of Liability for Medical Accidents: From Negligence to Strict Liability by Way of Informed Consent, 56 NEB. L. REV. 51, 124, 131-32 (1977)Google ScholarPubMed (arguing that this tort claim has come to approximate a rule of strict liability).

10 See Lawrence K. Altman, The Wrong Foot, and Other Tales of Surgical Error, N.Y. TIMES, Dec. 11, 2001, at F1; David Brown, Surgical Calamities on Rise, Group Says: Reports of Doctors Operating on Wrong Body Part—or Patient—Have Increased, WASH. POST, Dec. 6, 2001, at A14.

11 See, e.g., Ashcraft v. King, 278 Cal. Rptr. 900, 904-06 (Ct. App. 1991); Chouinard v. Marjani, 575 A.2d 238, 242 (Conn. Ct. App. 1990); Roberson v. Provident House, 576 So. 2d 992, 994 (La. 1991); Perna v. Priozzi, 457 A.2d 431, 438-39 (N.J. 1983); Blanchard v. Kellum, 975 S.W.2d 522, 524-25 (Tenn. 1998); see also Bloskas v. Murray, 646 P.2d 907, 915 (Colo. 1982) (distinguishing negligent misrepresentation claim from liability for failing to secure informed consent); Ludington, John P., Annotation, Medical Malpractice: Liability Based on Misrepresentation of the Nature and Hazards of Treatment, 42 A.L.R.4th 543 (1985 & Supp. 2002)Google Scholar.

12 See Washington v. Glucksberg, 521 U.S. 702, 724-25 (1997); Salgo v. Leland Stanford Jr. Univ. Bd. of Trustees, 317 P.2d 170, 181 (Cal. Ct. App. 1957) (“A physician violates his duty to his patient and subjects himself to liability if he withholds any facts which are necessary to form the basis of an intelligent consent by the patient to the proposed treatment.”); Schloendorff v. Society of New York Hosp., 105 N.E. 92, 93 (N.Y. 1914) (Cardozo, J.) (“Every human being of adult years and sound mind has a right to determine what shall be done with his own body; and a surgeon who performs an operation without his patient's consent commits an assault, for which he is liable in damages.”); see also RUTH R. FADEN & TOM L. BEAUCHAMP, A HISTORY AND THEORY OF INFORMED CONSENT 235-73, 294 (1986) (“[T]he primary moral justification of the obligation to obtain informed consent is the principle of respect for autonomy … .”); Gatter, Ken Marcus, Protecting Patient-Doctor Discourse: Informed Consent and Deliberative Autonomy, 78 OR. L. REV. 941, 961-82 (1999)Google ScholarPubMed (focusing on the constitutional foundations for respecting patient autonomy).

13 See Cassileth, Barrie R. et al., Informed Consent—Why Are Its Goals Imperfectly Realized?, 302 NEW ENG. J. MED. 896, 899 (1980)CrossRefGoogle ScholarPubMed; Katz, Jay, Informed Consent—Must It Remain a Fairy Tale?, 10 J. CONTEMP. HEALTH L. & POL’Y 69, 81, 84 (1994)Google ScholarPubMed (arguing that informed consent will remain a “charade” unless and until the medical profession embraces genuinely cooperative decision-making with patients); Lidz, Charles W. et al., Barriers to Informed Consent, 99 ANNALS INTERNAL MED. 539, 543 (1983)CrossRefGoogle ScholarPubMed; Meisel, Alan & Roth, Loren H., Toward an Informed Discussion of Informed Consent: A Review and Critique of the Empirical Studies, 25 ARIZ. L. REV. 265, 334-37 (1983)Google ScholarPubMed; Merz, Jon F. & Fischhoff, Baruch, Informed Consent Does Not Mean Rational Consent: Cognitive Limitations on Decision-Making, 11 J. LEGAL MED. 321, 349 (1990)CrossRefGoogle Scholar. See generally Jeremy Sugarman et al., Empirical Research on Informed Consent: An Annotated Bibliography, HASTINGS CTR. REP., Jan.- Feb. 1999, at S1.

14 See Duffy, Thomas P., Agamemnon's Fate and the Medical Profession, 9 W. NEW ENG. L. REV. 21 (1987)Google ScholarPubMed; Dworkin, Roger B., Medical Law and Ethics in the Post-Autonomy Age, 68 IND. L.J. 727, 735, 741-42 & n.69 (1993)Google ScholarPubMed; Mark, Jennifer S. & Spiro, Howard, Informed Consent for Colonoscopy: A Prospective Study, 150 ARCHIVES INTERNAL MED. 777, 780 (1990)CrossRefGoogle ScholarPubMed (“[A]utonomous decision making by an informed and self-sufficient patient is probably rarer in clinical practice than in philosophical suggestion.”); Fajfar, Mark, Note, An Economic Analysis of Informed Consent to Medical Care, 80 GEO. L.J. 1941, 1960-61 (1992)Google ScholarPubMed.

15 See Jones, Cathy J., Autonomy and Informed Consent in Medical Decisionmaking: Toward a New Self-Fulfilling Prophecy, 47 WASH. & LEE L. REV. 379, 397-406, 427-30 (1990)Google Scholar; Katz, Jay, Informed Consent—A Fairy Tale? Law's Vision, 39 U. PITT. L. REV. 137, 147 (1977)Google Scholar (“[J]udges’ sole focus on disclosure, to the exclusion of consent, tends to perpetuate physicians’ disengaged monologues and to discourage a meaningful dialogue between doctors and patients.”); id. at 159-60 (“[S]afeguarding self-determination requires asking the patient whether he understands what has been explained to him in order to assess whether his informational needs have been satisfied.”); id. at 170 (“Judges toyed briefly with the idea of patients’ self-determination and largely cast it aside.”); Kurtz, Sheldon F., The Law of Informed Consent: From “Doctor Is Right” to “Patient Has Rights”, 50 SYRACUSE L. REV. 1243, 1245, 1260 (2000)Google Scholar; Meisel, Alan, A “Dignitary Tort” as a Bridge Between the Idea of Informed Consent and the Law of Informed Consent, 16 LAW MED. & HEALTH CARE 210 (1988)CrossRefGoogle ScholarPubMed; Weisbard, Alan J., Informed Consent: The Law's Uneasy Compromise with Ethical Theory, 65 NEB. L. REV. 749, 751 (1986)Google ScholarPubMed (“[T]he law has been far richer in its rhetorical devotion to the ideal of patient self-determination than in its provision of effective legal redress to victimized patients.”).

16 See JAY KATZ, THE SILENT WORLD OF DOCTOR AND PATIENT 1-29 (1984); Waitzkin, Howard, Doctor-Patient Communication: Clinical Implications of Social Scientific Research, 252 JAMA 2441, 2446 (1984)CrossRefGoogle ScholarPubMed.

17 See Braddock, Clarence H. et al., Informed Decision Making in Outpatient Practice: Time to Get Back to Basics, 282 JAMA 2313 (1999)CrossRefGoogle ScholarPubMed; Emanuel, Ezekiel J. & Emanuel, Linda L., Four Models of the Physician-Patient Relationship, 267 JAMA 2221, 2225-26 (1992)CrossRefGoogle ScholarPubMed; Laine, Christine & Davidoff, Frank, Patient-Centered Medicine: A Professional Evolution, 275 JAMA 152, 154-55 (1996)CrossRefGoogle ScholarPubMed; Quill, Timothy E. & Brody, Howard, Physician Recommendations and Patient Autonomy: Finding a Balance Between Physician Power and Patient Choice, 125 ANNALS INTERNAL MED. 763, 768 (1996)CrossRefGoogle ScholarPubMed; see also STEPHEN WEAR, INFORMED CONSENT: PATIENT AUTONOMY AND PHYSICIAN BENEFICENCE WITHIN HEALTH CARE 171-79 (2d ed. 1998); Piper, August Jr., Truce on the Battlefield: A Proposal for a Different Approach to Medical Informed Consent, 22 J.L. MED. & ETHICS 301, 309-11 (1994)CrossRefGoogle ScholarPubMed; Robert M. Veatch, Abandoning Informed Consent, HASTINGS CTR. REP., Mar.-Apr. 1995, at 5, 12 (concluding that “[t]he concept of consent will have to be replaced with a more radical, robust notion of active patient participation in the choice among plausible alternatives”).

18 See Morgan v. MacPhail, 704 A.2d 617, 619-20 (Pa. 1997); see also Shadrick v. Coker, 963 S.W.2d 726, 732-33 (Tenn. 1998) (treating the failure to secure informed consent as a claim for battery). Along similar lines, some courts only require consent for the entire procedure rather than for each element. See Wachter v. United States, 689 F. Supp. 1420, 1423-24 (D. Md. 1988), aff’d, 877 F.2d 257, 260-61 (4th Cir. 1989); Van Iperen v. Van Bramer, 392 N.W.2d 480, 484 (Iowa 1986); Sinclair v. Block, 633 A.2d 1137, 1140 (Pa. 1993); Cary v. Arrowsmith, 777 S.W.2d 8, 21 (Tenn. Ct. App. 1989).

19 See Matthies v. Mastromonaco, 733 A.2d 456, 460-61 (N.J. 1999) (holding that a physician who prescribed bed-rest as treatment for a fractured hip had a duty to secure informed consent by advising the patient of surgical alternatives).

20 See, e.g., Hutchinson v. United States, 915 F.2d 560, 562-63 (9th Cir. 1990) (holding that doctor was liable for not warning patient of risks involved with use of asthma medication); Harbeson v. Parke Davis, Inc., 746 F.2d 517, 521, 525 (9th Cir. 1984) (holding, on an informed consent claim, that the doctors should have disclosed a drug's risk of causing birth defects); Summit Bank v. Panos, 570 N.E.2d 960, 967-68 (Ind. Ct. App. 1991); Calabrese v. Trenton State College, 392 A.2d 600, 605- 06 (N.J. Super. Ct. 1978), aff’d, 413 A.2d 315 (N.J. 1980); Sharpe v. Pugh, 155 S.E.2d 108, 112-13 (N.C. 1967); Barclay v. Campbell, 704 S.W.2d 8, 9-10 (Tex. 1986); Trogun v. Fruchtman, 207 N.W.2d 297, 313 (Wis. 1973); see also Tietz, Gerald F., Informed Consent in the Prescription Drug Context: The Special Case, 61 WASH. L. REV. 367, 395-417 (1986)Google ScholarPubMed (urging stricter application of the informed consent duty with respect to prescribing); Sharp, Linda A., Annotation, Malpractice: Physician's Liability for Injury or Death Resulting from Side Effects of Drugs Intentionally Administered to or Prescribed for Patients, 47 A.L.R.5th 433 (1997 & Supp. 2002)Google Scholar.

21 See, e.g., Hezeau v. Pendleton Methodist Mem’l Hosp., 715 So. 2d 756, 760-62 (La. Ct. App. 1998); Rizzo v. Schiller, 445 S.E.2d 153, 155 (Va. 1994).

22 See Tresemer v. Barke, 150 Cal. Rptr. 384, 392-94 (Ct. App. 1978); Gorab v. Zook, 943 P.2d 423, 430 (Colo. 1997); Tanuz v. Carlberg, 921 P.2d 309, 313, 316 (N.M. Ct. App. 1996); Nadel, Andrea G., Annotation, Duty of Medical Practitioner to Warn Patient of Subsequently Discovered Danger from Treatment Previously Given, 12 A.L.R.4th 41 (1982 & Supp. 2002)Google Scholar; see also Schreiber v. Physicians Ins. Co., 588 N.W.2d 26, 31-33 (Wis. 1999) (holding that a patient may withdraw consent in the middle of a procedure, which then would require a new round of disclosure). Although entirely consistent with a seller's ongoing duty to warn in products liability cases, such a requirement would not exist under a theory of battery.

23 See, e.g., Logan v. Greenwich Hosp. Ass’n, 465 A.2d 294, 301-02 (Conn. 1983); Doe v. Johnston, 476 N.W.2d 28, 31 (Iowa 1991); Wecker v. Amend, 918 P.2d 658, 661-62 (Kan. Ct. App. 1996); Kalsbeck v. Westview Clinic, 375 N.W.2d 861, 869 (Minn. Ct. App. 1985); Herrington v. Spell, 692 So. 2d 93, 100 (Miss. 1997); Matthies v. Mastromonaco, 733 A.2d 456, 461-64 (N.J. 1999); Smith v. Reisig, 686 P.2d 285, 288 (Okla. 1984); Zacher v. Petty, 826 P.2d 619, 621 (Or. 1992); Stover v. Association of Thoracic & Cardiovascular Surgeons, 635 A.2d 1047, 1050-52 (Pa. Super. Ct. 1993); Keogan v. Holy Family Hosp., 622 P.2d 1246, 1255-56 (Wash. 1980); Martin v. Richards, 531 N.W.2d 70, 75-81 (Wis. 1995); see also Krause, Joan H., Reconceptualizing Informed Consent in an Era of Health Care Cost Containment, 85 IOWA L. REV. 261, 305-37 (1999)Google Scholar (explaining the practical limitations of this aspect of the duty to secure informed consent); Derrick, John H., Annotation, Medical Malpractice: Liability for Failure of Physician to Inform Patient of Alternative Modes of Diagnosis or Treatment, 38 A.L.R.4th 900 (1985 & Supp. 2002)Google Scholar.

24 See Truman v. Thomas, 611 P.2d 902, 906-07 (Cal. 1980); Moore v. Preventive Medicine Med. Group, Inc., 223 Cal. Rptr. 859, 862-64 (Ct. App. 1986); Battenfeld v. Gregory, 589 A.2d 1059, 1066 (N.J. Super. Ct. App. Div. 1991); Gates v. Jensen, 595 P.2d 919, 922 (Wash. 1979); see also Brock, Dan W. & Wartman, Steven A., When Competent Patients Make Irrational Choices, 322 NEW ENG. J. MED. 1595, 1595 (1990)CrossRefGoogle ScholarPubMed (“[E]ven the irrational choices of a competent patient must be respected if the patient cannot be persuaded to change them.”). But cf. McGeshick v. Choucair, 9 F.3d 1229, 1233- 35 (7th Cir. 1993); Turner v. Children's Hosp., Inc., 602 N.E.2d 423, 431 (Ohio Ct. App. 1991) (“This doctrine has not emerged to educate the patient generally on medical matters.”).

25 See Schuck, supra note 7, at 910 (“[A] health care provider's obligations toward patients are in several respects more onerous than … those that product manufacturers and sellers owe to their purchasers and consumers.”); id. at 921-23 (elaborating); see also Songer v. Bowman, 804 P.2d 261, 263-64 (Colo. Ct. App. 1990) (holding that, even though plaintiff did not assert an informed consent claim, a dermatologist could be found negligent for failing to instruct the patient to avoid sun exposure when using topical prescription drug); Tenuto v. Lederle Labs., 687 N.E.2d 1300, 1302-04 (N.Y. 1997) (physician had a duty to warn plaintiff of risk of contracting polio from child who had received a vaccine).

26 See Henderson v. Milobsky, 595 F.2d 654, 658 (D.C. Cir. 1978) (holding that a surgeon did not need to disclose a 0.001% risk of permanent loss of sensation in a small section of the plaintiff's face); Feeley v. Baer, 679 N.E.2d 180, 181-82 (Mass. 1997); Britain, James E., Product Honesty Is the Best Policy: A Comparison of Doctors’ and Manufacturers’ Duty to Disclose Drug Risks and the Importance of Consumer Expectations in Determining Product Defect, 79 NW. U. L. REV. 342, 389 (1984)Google Scholar (“[W]hile it would be foolhardy to assert that a bright line between the material and immaterial can be drawn at one percent probability and high severity of risk, a substantial body of case law suggests that the duty of physician disclosure is often triggered by risks approximating that order of magnitude.”).

27 See Ketchup v. Howard, 543 S.E.2d 371, 378, 381-86 (Ga. Ct. App. 2000) (appending a state-by-state survey); Merz, Jon F., On a Decision-Making Paradigm of Medical Informed Consent, 14 J. LEGAL MED. 231, 243-64 (1993)CrossRefGoogle ScholarPubMed; Frantz, Laurent B., Annotation, Modern Status of Views as to General Measure of Physician's Duty to Inform Patient of Risks of Proposed Treatment, 88 A.L.R.3d 1008 (1978 & Supp. 2002)Google Scholar.

28 See, e.g., Craig v. Borcicky, 557 So. 2d 1253, 1258 (Ala. 1990); Fuller v. Starnes, 597 S.W.2d 88, 89-90 (Ark. 1980); Shabinaw v. Brown, 963 P.2d 1184, 1188-94 (Idaho 1998); Culbertson v. Mernitz, 602 N.E.2d 98, 101, 103-04 (Ind. 1992); Ziegert v. South Chicago Community Hosp., 425 N.E.2d 450, 458-59 (Ill. App. Ct. 1981); Woolley v. Henderson, 418 A.2d 1123, 1128-31 (Me. 1980); Paul v. Lee, 568 N.W.2d 510, 514-16 (Mich. 1997); Robinson v. Bleicher, 559 N.W.2d 473, 478 (Neb. 1997); Hook v. Rothstein, 316 S.E.2d 690, 695-98 (S.C. Ct. App. 1984); Weber v. McCoy, 950 P.2d 548, 552 (Wyo. 1997).

29 See Canterbury v. Spence, 464 F.2d 772, 781 (D.C. Cir. 1972) (“[I]t is the prerogative of the patient, not the physician, to determine for himself the direction in which his interests seem to lie.”); Cobbs v. Grant, 502 P.2d 1, 9-11 (Cal. 1972); Largey v. Rothman, 540 A.2d 504, 508-09 (N.J. 1988).

30 See, e.g., Truman v. Thomas, 611 P.2d 902, 905 (Cal. 1980) (“Material information is that which the physician knows or should know would be regarded as significant by a reasonable person in the patient's position when deciding to accept or reject the recommended medical procedure.”); Carr v. Strode, 904 P.2d 489, 494-99 (Haw. 1995); Rook v. Trout, 747 P.2d 61, 66-67 (Idaho 1987); Pauscher v. Iowa Methodist Med. Ctr., 408 N.W.2d 355, 361-62 (Iowa 1987); Cowman v. Hornaday, 329 N.W.2d 422, 425-27 (Iowa 1983); Harnish v. Children's Hosp. Med. Ctr., 439 N.E.2d 240, 242-44 (Mass. 1982); Phillips v. Hull, 516 So. 2d 488, 493-94 (Miss. 1987); Wilkinson v. Vesey, 295 A.2d 676, 688-90 (R.I. 1972); Wheeldon v. Madison, 374 N.W.2d 367, 374-75 (S.D. 1985).

31 See Hartke v. McKelway, 707 F.2d 1544, 1548-49 (D.C. Cir. 1983); Korman v. Mallin, 858 P.2d 1145, 1150-51 (Alaska 1993); Lugenbuhl v. Dowling, 676 So. 2d 602, 605-06 (La. Ct. App. 1996); Macy v. Blatchford, 8 P.3d 204, 209-11 (Or. 2000).

32 See Kennis v. Mercy Hosp. Med. Ctr., 491 N.W.2d 161, 166 (Iowa 1992); Sard v. Hardy, 379 A.2d 1014, 1024 (Md. 1977); Festa v. Greenberg, 511 A.2d 1371, 1376-78 (Pa. Super. Ct. 1986); Cross v. Trapp, 294 S.E.2d 446, 455 (W. Va. 1982); see also Reiser v. Lehner, 641 P.2d 93, 99 (Utah 1982) (no duty to disclose unknowable risk).

33 See Carr v. Strode, 904 P.2d 489, 500 (Haw. 1995); Frost v. Brenner, 693 A.2d 149, 155 (N.J. Super. Ct. App. Div. 1997); Savold v. Johnson, 443 N.W.2d 656, 659 (S.D. 1989); Cross v. Trapp, 294 S.E.2d 446, 455 (W. Va. 1982).

34 See Sard v. Hardy, 379 A.2d 1014, 1022 (Md. 1977); Meisel, Alan, The “Exceptions” to the Informed Consent Doctrine: Striking a Balance Between Competing Values in Medical Decisionmaking, 1979 WIS. L. REV. 413, 434-70Google Scholar (discussing the exceptions for emergencies, incompetence, waiver, and the therapeutic privilege).

35 See Cobbs v. Grant, 502 P.2d 1, 12 (Cal. 1972); Nishi v. Hartwell, 473 P.2d 116, 119-21 (Haw. 1970). In fact, researchers have found that some patients experience suggestion-induced side effects when informed of risks. See Brian Reid, The Nocebo Effect: Placebo's Evil Twin, WASH. POST, Apr. 30, 2002, at Z1.

36 See Canterbury v. Spence, 464 F.2d 772, 789 (D.C. Cir. 1972); Somerville, Margaret A., Therapeutic Privilege: Variation on the Theme of Informed Consent, 12 LAW MED. & HEALTH CARE 4, 5-6 (1984)CrossRefGoogle ScholarPubMed.

37 See Pardy v. United States, 783 F.2d 710, 715 (7th Cir. 1986); Parkins v. United States, 834 F. Supp. 569, 574 (D. Conn. 1993); Salis v. United States, 522 F. Supp. 989, 1002-05 (M.D. Pa. 1981); Fore v. Brown, 544 So. 2d 955, 956 (Ala. 1989); Bernard v. Char, 903 P.2d 667, 671-76 (Haw. 1995); Sard v. Hardy, 379 A.2d 1014, 1025-26 (Md. 1977); Wilkerson v. Mid-America Cardiology, 908 S.W.2d 691, 696-99 (Mo. Ct. App. 1995); Smith v. Cotter, 810 P.2d 1204, 1209 (Nev. 1991); Posta v. Chung-Loy, 703 A.2d 368, 379 (N.J. Super. Ct. App. Div. 1997); Nickell v. Gonzalez, 477 N.E.2d 1145, 1148 (Ohio 1985); Ashe v. Radiation Oncology Assocs., 9 S.W.3d 119, 122-24 (Tenn. 1999); Backlund v. Univ. of Washington, 975 P.2d 950, 957-59 (Wash. 1999); Seidelson, David E., Lack of Informed Consent in Medical Malpractice and Product Liability Cases: The Burden of Presenting Evidence, 14 HOFSTRA L. REV. 621, 622-40 (1986)Google Scholar. See generally Strassfeld, Robert N., If … : Counterfactuals in the Law, 60 GEO. WASH. L. REV. 339 (1992)Google Scholar.

38 See Katz, supra note 15, at 163 (“The ‘objective’ standard of ‘causality’ contradicts the right of each individual to decide what will be done with his body by denying the patient recovery whenever his hypothetical decision is out of step with the judgment of a prudent person.”); Twerski, Aaron D. & Cohen, Neil B., Informed Decision Making and the Law of Torts: The Myth of Justiciable Causation, 1988 U. ILL. L. REV. 607, 613-21Google Scholar.

39 See Arato v. Avedon, 858 P.2d 598, 608-09 (Cal. 1993); Kimmel v. Dayrit, 693 A.2d 1287, 1296 (N.J. Super. Ct. App. Div. 1997).

40 See Kassirer, Jerome P., Editorial, Incorporating Patients’ Preferences into Medical Decisions, 330 NEW ENG. J. MED. 1895, 1895 (1994)CrossRefGoogle ScholarPubMed. Patients also may have preferences that deviate from those assumed by healthcare providers. See Redelmeier, Donald A. et al., Understanding Patients’ Decisions: Cognitive and Emotional Perspectives, 270 JAMA 72 (1993)CrossRefGoogle ScholarPubMed; Rich, Ben A., The Values History: A New Standard of Care, 40 EMORY L.J. 1109, 1141-52 (1991)Google ScholarPubMed.

41 See McPherson v. Ellis, 287 S.E.2d 892, 897 & n.2 (N.C. 1982) (conceding, however, that new legislation imposed an objective standard for claims arising after its date of enactment); Scott v. Bradford, 606 P.2d 554, 559 (Okla. 1979); Gouse v. Cassel, 615 A.2d 331, 333-35 (Pa. 1992) (treating the failure to secure informed consent as a form of battery for which causation would not be required); see also Fain v. Smith, 479 So. 2d 1150, 1155 (Ala. 1985) (“We note, however, that the objective standard requires consideration by the factfinder of what a reasonable person with all of the characteristics of the plaintiff, including his idiosyncracies and religious beliefs, would have done under the same circumstances.”); Zalazar v. Vercimak, 633 N.E.2d 1223, 1225-27 (Ill. App. Ct. 1993) (adopting a subjective standard for claims involving elective cosmetic surgery); Arena v. Gingrich, 748 P.2d 547, 548-50 (Or. 1988); Schreiber v. Physicians Ins. Co., 588 N.W.2d 26, 34 (Wis. 1999) (adopting a subjective standard only in cases where patient had expressed a clear preference at the time of the procedure).

42 See Andrews, Lori B., Informed Consent Statutes and the Decisionmaking Process, 5 J. LEGAL MED. 163, 178-80, 186, 195-98, 206-16 (1984)CrossRefGoogle ScholarPubMed (discussing statutes enacted in twenty-three states); Meisel, Alan & Kabnick, Lisa D., Informed Consent to Medical Treatment: An Analysis of Recent Legislation, 41 U. PITT. L. REV. 407, 410 (1980)Google ScholarPubMed (noting that in the mid-1970s, in response to widespread concerns about a medical malpractice crisis, “twenty-four states enacted legislation dealing with informed consent”); id. at 563 (concluding “that, in the overwhelming majority of cases, the informed consent statutes are little more than window-dressing, creating the appearance of change without the substance”); see also Rubino v. DeFretias, 638 F. Supp. 182, 185 (D. Ariz. 1986) (invalidating one such statute on state constitutional grounds); Albany Urology Clinic, P.C. v. Cleveland, 528 S.E.2d 777, 779-80 (Ga. 2000) (explaining that the Georgia statute created an informed consent duty not previously recognized at common law in that state).

43 See, e.g., ARK. CODE ANN. § 16-114-206(b)(1) (1987); DEL. CODE ANN. tit. 18, § 6852(a)(2) (1999); KY. REV. STAT. ANN. § 304.40-320(1) (2001); NEB. REV. STAT. § 44-2816 (1998); N.H. REV. STAT. ANN. § 507-C:2(II) (1997); N.Y. PUB. HEALTH LAW § 2805-d(1) (2002); TENN. CODE ANN. § 29-26-118 (2000); VT. STAT. ANN. tit. 12, § 1909(a)(1) (2001). But see PA. STAT. ANN. tit. 40, § 1301.811-A(b) (1999) (codifying the patient standard); WASH. REV. CODE § 7.70.050(2) (1992).

44 See HAW. REV. STAT. § 671-3(b) (1993); LA. REV. STAT. ANN. 40:1299.40(E) (2001 & Supp. 2002); TEX. REV. CIV. STAT. ANN. art. 4590i(F) (West Supp. 2002); TEX. ADMIN. CODE tit. 25, pt. 601 (2001); Earle v. Ratliff, 998 S.W.2d 882, 891 (Tex. 1999); see also Krause, supra note 23, at 379-85 (discussing statutes in a number of states that require physicians to disclose alternative treatments to breast cancer patients).

45 See Bottrell, Melissa M. et al., Hospital Informed Consent for Procedure Forms: Facilitating Quality Patient-Physician Interaction, 135 ARCHIVES SURGERY 26, 26-27, 30 (2000)CrossRefGoogle ScholarPubMed; Hopper, Kenneth D. et al., The Readability of Currently Used Surgical/Procedure Consent Forms in the United States, 123 SURGERY 496, 499-502 (1998)CrossRefGoogle ScholarPubMed; Meisel, Alan & Kuczewski, Mark, Legal and Ethical Myths About Informed Consent, 156 ANNALS INTERNAL MED. 2521, 2522 (1996)CrossRefGoogle ScholarPubMed (“As practiced, and certainly as symbolized by consent forms, informed consent is often no more than a medical Miranda warning.”). Because of concerns about the effectiveness of such consent forms, some commentators have proposed other methods of communicating relevant information. See O’Connor, Annette M. et al., Decision Aids for Patients Facing Health Treatment or Screening Decisions: Systematic Review, 319 BRIT. MED. J. 731, 733 (1999)CrossRefGoogle ScholarPubMed; Rosoff, Arnold J., Informed Consent in the Electronic Age, 25 AM. J.L. & MED. 367, 372-78 (1999)CrossRefGoogle ScholarPubMed (describing the movement toward interactive computer-based patient education systems); id. at 383-85 (warning that a canned or ritualized approach to informed consent can “stifle the dynamic human interaction” between physician and patient).

46 See FLA. STAT. ANN. § 766.103(4) (2001); GA. CODE ANN. § 31-9-6(d) (2001); IDAHO CODE § 39-4305 (1998); IOWA CODE ANN. § 147.137 (1997); MAINE REV. STAT. ANN. tit. 24, § 2905(2) (2000); NEV. REV. STAT. § 41A.110(4) (1996 & Supp. 2001); N.C. GEN. STAT. § 90-21.13(b) (1999); OHIO REV. CODE § 2317.54 (2001); UTAH CODE ANN. § 78-14-5(2)(e) (1996 & Supp. 2001); WASH. REV. CODE ANN. § 7.70.060 (1992); see also Cardio TVP Surgical Assocs. v. Gillis, 528 S.E.2d 785, 787-88 (Ga. 2000); Parikh v. Cunningham, 493 So. 2d 999, 1001-02 (Fla. 1986); Hondroulis v. Schuhmacher, 553 So. 2d 398, 417-22 (La. 1988); Allan v. Levy, 846 P.2d 274, 275 (Nev. 1993); Meisel & Kabnick, supra note 42, at 467-77, 561 (noting “the unfortunate tendency of organized medicine to view informed consent as nothing more than a legal hurdle to be surmounted by a consent form”).

47 See Hartsell v. Fort Sanders Reg’l Med. Ctr., 905 S.W.2d 944, 947 (Tenn. Ct. App. 1995) (holding that a signed consent form only defeated a battery claim); cf. Schneider v. Revici, 817 F.2d 987, 993-96 (2d Cir. 1987) (holding that an informed consent form did not unambiguously waive the right to sue a physician for malpractice after treating breast cancer patient non-invasively with selenium supplements, but allowing express assumption of risk defense); id. at 995 (“[W]e see no reason why a patient should not be allowed to make an informed decision to go outside currently approved medical methods in search for an unconventional treatment… . [A]n informed decision to avoid surgery and conventional chemotherapy is within the patient's right … .”); Brown v. Dibbell, 595 N.W.2d 358, 367-70 (Wis. 1999) (holding that comparative negligence would rarely serve as a defense to an informed consent claim); Miller, Caroll J., Annotation, Patient's Failure to Reveal Medical History to Physician as Contributory Negligence or Assumption of Risk in Defense of Malpractice Action, 33 A.L.R.4th 790 (1983 & Supp. 2002)Google Scholar. Courts generally refuse to enforce such waivers in the healthcare context. See Tunkl v. Regents of the Univ. of Cal., 383 P.2d 441, 447 (Cal. 1963); Emory Univ. v. Porubiansky, 282 S.E.2d 903, 905 (Ga. 1981); Cudnik v. William Beaumont Hosp., 525 N.W.2d 891, 895-96 (Mich. Ct. App. 1994); Ash v. New York Univ. Dental Ctr., 564 N.Y.S.2d 308, 310-13 (App. Div. 1990); see also Mehlman, Maxwell J., Fiduciary Contracting: Limitations on Bargaining Between Patients and Health Care Providers, 51 U. PITT. L. REV. 365, 401-06 (1990)Google Scholar.

48 See Schuck, supra note 7, at 906, 954-55; see also Capron, supra note 7, at 392, 408, 411- 13 (arguing in favor of using a subjective standard for judging informed consent in the research context); Katz, Jay, Physician-Patient Encounters “On a Darkling Plain”, 9 W. NEW ENG. L. REV. 207, 221-23 (1987)Google Scholar (suggesting, for instance, differentiating between elective procedures and interventions for acute disorders that require prompt attention). See generally Wolf, Susan M., Shifting Paradigms in Bioethics and Health Law: The Rise of a New Pragmatism, 20 AM. J.L. & MED. 395, 411-14 (1994)CrossRefGoogle ScholarPubMed.

49 See Adams, Bernard R. & Shea-Stonum, Marilyn, Toward a Theory of Control of Medical Experimentation with Human Subjects: The Role of Compensation, 25 CASE W. RES. L. REV. 604, 616-24 (1975)Google Scholar; Delgado, Richard & Leskovac, Helen, Informed Consent in Human Experimentation: Bridging the Gap Between Ethical Thought and Current Practice, 34 UCLA L. REV. 67, 68 n.1 (1986)Google ScholarPubMed (agreeing with those who argue that “there is a single informed consent requirement, which is applied more rigorously in experimental settings because of the greater dangers those settings pose to autonomy and well-being,” rather than with those who argue that “there are two separate requirements, one applicable to experimental settings, the other applicable to settings in which standard therapies are dispensed,” but concluding that, “[o]perationally, there is little difference between the two conceptions of informed consent”).

50 See Delgado & Leskovac, supra note 49, at 69; see also id. at 88-112 (evaluating these and related rationales); id. at 129 (“Most writers, and the few courts that have considered the question, maintain that informed consent should be protected more highly in research settings than in those settings in which standard medical or behavioral treatments are dispensed.”); King, Nancy M.P. & Henderson, Gail, Treatments of Last Resort: Informed Consent and the Diffusion of New Technology, 42 MERCER L. REV. 1007, 1028 (1991)Google ScholarPubMed (“[W]ithout this recognition [as research], experimental technologies will be treated like standard therapy, with neither patients nor caregivers able to account for relevant differences in risks, the increased chance of unknown risks and harms, and the lack of data regarding potential benefits.”); id. at 1044-45 (same).

51 See Levine, Robert J., Informed Consent in Research and Practice: Similarities and Differences, 143 ARCHIVES INTERNAL MED. 1229, 1230 (1983)CrossRefGoogle Scholar. Even if still accurate, this could cut the other way insofar as a patient may be less likely to question the recommendations of a trusted family physician than a clinical investigator with whom they have only a single encounter. See Capron, supra note 7, at 386.

52 See, e.g., infra Part III. Similar arguments purport to justify imposing a greater duty to disclose on physicians than on sellers of consumer products. See Schuck, supra note 7, at 924-39 (rebutting arguments based on autonomy, relational continuity, conflicts of interest, inequalities in information and power, and utility). For instance, Professor Schuck points out that “the idealized vision of physician-patient interactions” has lost out to “episodic transactions” that resemble commercial sales. See id. at 926 (“[T]he traditional image of the intimate, protracted relationship between physician and patient has grown increasingly anachronistic.”); see also id. (adding that informed consent issues tend to arise in the context of treatment by specialists: “Surgery often (and hopefully) involves only a one-time encounter.”); Shultz, Marjorie Maguire, From Informed Consent to Patient Choice: A New Protected Interest, 95 YALE L.J. 219, 269-75 (1985)CrossRefGoogle ScholarPubMed (arguing that conflicts of interest and medical uncertainty justify a more protective informed consent doctrine in the treatment setting). For purposes of this Article, such developments also might undercut some of the rationales advanced for imposing an even more rigorous duty to secure informed consent in the research setting.

53 See Salgo v. Leland Stanford Jr. Univ. Bd. of Trustees, 317 P.2d 170, 175, 180 (Cal. Ct. App. 1957) (translumbar aortography injecting a higher than recommended dosage of sodium urokon as a contrast medium). The more definitive first expression of the modern informed consent doctrine also involved the use of a fairly novel intervention, though nothing explicitly turned on that fact. See Natanson v. Kline, 350 P.2d 1093, 1101 (Kan. 1960). For a still earlier opinion alluding to this issue, see Fortner v. Koch, 261 N.W. 762, 765 (Mich. 1935) (“We recognize the fact that, if the general practice of medicine and surgery is to progress, there must be a certain amount of experimentation carried on; but such experiments must be done with the knowledge and consent of the patient … and must not vary too radically from the accepted method of procedure.”).

54 See Alvarez v. Smith, 714 So. 2d 652, 655 (Fla. Ct. App. 1998); Klein v. Biscup, 673 N.E.2d 225, 231 (Ohio Ct. App. 1996) (“Off-label use of a medical device is not a material risk inherently involved in a proposed therapy which a physician should disclose to a patient prior to therapy.”); Southard v. Temple Univ. Hosp., 781 A.2d 101, 107-08 (Pa. 2001); Ramon v. Farr, 770 P.2d 131, 135-37 (Utah 1989); see also Beck, James M. & Azari, Elizabeth D., FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions, 53 FOOD & DRUG L.J. 71, 100-01 (1998)Google ScholarPubMed (arguing that physicians should not have any tort duty to disclose a product's regulatory status).

55 See Corrigan v. Methodist Hosp., 869 F. Supp. 1202, 1207 (E.D. Pa. 1994) (adding that a jury might find this experimental use sufficiently outrageous to justify an award of punitive damages); Retkwa v. Orentreich, 584 N.Y.S.2d 710, 712-13 (Sup. Ct. 1992) (silicone injections); Shadrick v. Coker, 963 S.W.2d 726, 729-30, 734-35, 736-37 (Tenn. 1998) (reversing summary judgment granted to a physician who allegedly had failed to inform the patient that the FDA had not approved the use of pedicle screws in spinal surgery); see also PA. STAT. ANN., tit. 40, § 1301.811-A(a)(5) (1999) (requiring informed consent when “[a]dministering an experimental medication, using an experimental device, or using an approved medication or device in an experimental manner”); cf. Reetz v. Jackson, 176 F.R.D. 412, 415 (D.D.C. 1997) (noting that even if the lack of FDA approval would not have altered the plaintiff's decision to proceed, knowledge about the “experimental” nature of the pedicle screws might have done so).

56 See Robak v. Abbott Labs., 797 F. Supp. 475, 476 (D. Md. 1992) (“Certainly, no manufacturer need explicitly spell out all of the conditions for which a drug is not indicated.”); see also Richardson v. Miller, 44 S.W.3d 1, 8 n.2, 16-17 (Tenn. Ct. App. 2000) (holding that the trial judge had erred in excluding label that had specifically warned against the off-label use selected by the physician); Noah, Lars, Constraints on the Off-Label Uses of Prescription Drug Products, 16 J. PRODS. & TOXICS LIAB. 139, 159-62 (1994)Google Scholar (explaining the limits of pharmaceutical and medical device manufacturers’ duty to warn of risks associated with uses not approved by the FDA for inclusion in labeling); Stoffelmayr, Kaspar J., Comment, Products Liability and “Off-Label” Uses of Prescription Drugs, 63 U. CHI. L. REV. 275, 300 (1996)CrossRefGoogle Scholar (recommending that manufacturers only owe a duty to warn of demonstrated risks with off-label uses). But see Upjohn Co. MacMurdo, 562 So. 2d 680, 682-83 (Fla. 1990) (holding that a disclaimer that an off-label use remained investigational did not by itself satisfy the duty to warn of risks associated with that use); Proctor v. Davis, 682 N.E.2d 1203, 1212-15 (Ill. App. Ct. 1997). Indeed, one of the rationales for exempting prescription drugs from strict liability emphasized the fact that many such “unavoidably unsafe” products remain experimental. See RESTATEMENT (SECOND) OF THE LAW OF TORTS § 402A cmt. k (1965) (“It is also true in particular of many new or experimental drugs as to which, because of lack of time and opportunity for sufficient medical experience, there can be no assurance of safety … .”); see also Gaston v. Hunter, 588 P.2d 326, 339-40 (Ariz. Ct. App. 1978) (extending comment k protection to an investigational drug, but requiring clear disclosure of its experimental status).

57 460 F. Supp. 713 (N.D. Ill. 1978).

58 See id. at 717 (“The plaintiffs did not consent to DES treatment; they were not even aware that the drug was being administered to them. They were the subjects of an experiment … .”); id. at 717 n.3 (“[T]he plaintiffs were completely unaware of the DES treatment. Indeed the double-blind nature of the study resulted in affirmative concealment of the fact of drug treatment from the patients.”).

59 See id. at 718. The court did, however, dismiss the plaintiffs’ other claims because they had not themselves suffered any compensable physical injuries. See id.; see also Anderson v. George H. Lanier Mem. Hosp., 982 F.2d 1513, 1519-20 (11th Cir. 1993) (holding that the statute of limitations did not bar informed consent claims brought by cataract patients treated with the implantation of investigational intraocular lenses who did not initially know of their experimental status).

60 He explained the point as follows:

Chalmers, Iain, Letter, Human Guinea Pigs, 302 BRIT. MED. J. 411, 411 (1991).CrossRefGoogle Scholar

61 452 N.Y.S.2d 875 (App. Div. 1982).

62 See id. at 876-77.

63 See id. at 877-78.

64 See id. at 878.

65 See id. at 880-82 (reversing, however, the judgment rendered against the plaintiff's attending physician).

66 See id. at 880 (“[T]he hospital and Dr. Engle cannot avail themselves of the shield of acceptable medical practice when a number of studies, including their own, had already indicated that increased oxygen was both unnecessary and dangerous, particularly for an otherwise healthy baby, and especially when the attending physician, who had primary responsibility for the patient's health, had recommended a decrease.”); id. (“Furthermore, the jury had before it evidence that symptoms of RLF had begun to appear during the 28 day period of increased oxygen. Yet, the hospital permitted a healthy infant to remain in a precarious position after symptoms of a disease of which it was aware and, indeed, was studying, had been detected.”).

67 Id. at 879.

68 See id. at 880-81; see also Schwartz v. Boston Hosp. for Women, 422 F. Supp. 53, 55-56 (S.D.N.Y. 1976) (denying a motion for summary judgment on plaintiff's claim that she had not consented to an experimental procedure, though she had agreed to the use of records concerning her obstetrical treatment at a hospital participating in a national study of pregnant diabetics, because the court found “a fact question of whether the curettage was performed for purposes of the MIH study rather than to aid in the diagnosis and treatment of Mrs. Schwartz”).

69 588 P.2d 326 (Ariz. Ct. App. 1978).

70 See id. at 350.

71 Id. at 351 (adding that “the rule on informed consent is flexible enough to encompass dangerous or novel procedures”); see also Karp v. Cooley, 349 F. Supp. 827, 835 (S.D. Tex. 1972) (“[T]he specially prepared consent form did relate some of the detailed information that plaintiffs complain of, i.e., ‘I realize that this [mechanical heart] device has been tested in the laboratory but has not been used to sustain a human being and that no assurance of success can be made.’ … Accordingly, as to any issue of informed consent, a verdict must be directed for Dr. Cooley.”), aff’d, 493 F.2d 408, 419-23, 424 n.23 (5th Cir. 1974) (noting, without taking a position on the question, that “[s]ome commentators have suggested that the duty to preinform is viewed more strictly when a novel or radical medical procedure is involved”).

72 321 S.E.2d 240 (N.C. Ct. App. 1984).

73 See id. at 253 (“This knowledge, on the present record, is traceable exclusively to a single medical article and to the ill-defined experience of one of the radiologists, apparently including only one prior operation … . There was some evidence that steel coil embolizations had been used in other parts of the body with low risk, but nothing to show why that knowledge should automatically apply to the peripheral arteries operated on in this case.”); id. (“In their initial Answer, all defendants admitted that the embolization procedure was experimental. Although their Amended Answers denied this, the original Answer remained admissible against them.”); id. at 254 (finding “substantial evidence that the procedure as used was in fact experimental”).

74 Id. at 254 (“Our decision that health care providers must inform their patients that proposed procedures are experimental accords with the majority of courts and commentators which have considered the problem… . [W]e also follow the great bulk of the commentators.”).

75 See id. at 255 (“The psychology of the doctor-patient relation, and the rewards, financial and professional, attendant upon recognition of experimental success, increase the potential for abuse and strengthen the rationale for uniform disclosure.”).

76 Id. at 254 (“If the health care provider has a duty to inform of known risks for established procedures, common sense and the purposes of the statute equally require that the health care provider inform the patient of any uncertainty regarding the risks associated with experimental procedures.”).

77 See Ahern v. Veterans Admin., 537 F.2d 1098, 1101-02 (10th Cir. 1976) (affirming judgment for a plaintiff who had received far higher doses of radiation to treat cancer than anyone accepted as the standard of care, and holding that a “patient must always be fully informed of the experimental nature of the treatment”); Clemens v. Regents of the Univ. of Cal., 87 Cal. Rptr. 108, 114 (Ct. App. 1970); Fiorentino v. Wenger, 272 N.Y.S.2d 557, 559 (App. Div. 1966), aff’d, 227 N.E.2d 296 (N.Y. 1967).

78 See Hales v. Pittman, 576 P.2d 493, 500 (Ariz. 1978); Johnson v. Kokemoor, 545 N.W.2d 495, 504-10 (Wis. 1996). But see Ditto v. McCurdy, 947 P.2d 952, 958-59 (Haw. 1997) (no duty to disclose lack of special credentials); Leger v. Louisiana Med. Mut. Ins. Co., 732 So. 2d 654, 658 (La. Ct. App. 1999); Aceto v. Dougherty, 615 N.E.2d 188, 191 (Mass. 1993) (“‘The court does not read the law of informed consent to require a physician to raise the possibility … that he might perform the operation unskillfully.’”); Duttry v. Patterson, 771 A.2d 1255, 1258-59 (Pa. 2001); Whiteside v. Lukson, 947 P.2d 1263, 1265 (Wash. Ct. App. 1997) (“In theory, … even medical school grades could be considered material facts … . [W]e conclude that a surgeon's lack of experience in performing a particular surgical procedure is not a material fact for purposes of finding liability predicated on failure to secure an informed consent.”).

79 See Twerski, Aaron D. & Cohen, Neil B., The Second Revolution in Informed Consent: Comparing Physicians to Each Other, 94 NW. U. L. REV. 1, 3-5, 15-17 (1999)Google ScholarPubMed.

80 Cf. Twerski, Aaron D. & Cohen, Neil B., Comparing Medical Providers: A First Look at the New Era of Medical Statistics, 58 BROOK. L. REV. 5, 28-33, 34 (1992)Google Scholar (conceding the possibility that “intern and resident programs will be hampered by statistics which show that beginners do not perform as well as seasoned veterans”). See generally Gaster, Barak, The Learning Curve, 270 JAMA 1280 (1993)CrossRefGoogle ScholarPubMed (relating a story of one experienced surgeon's difficulties with a new laparoscopic procedure); Hartz, Arthur J. et al., Are the Best Coronary Artery Bypass Surgeons Identified by Physician Surveys?, 87 AM. J. PUB. HEALTH 1645, 1647-48 (1997)CrossRefGoogle ScholarPubMed (finding that surgical volume better predicts proficiency); Hofmann, Paul B. et al., Physician Experience as a Measure of Competency: Implications for Informed Consent, 5 CAMBRIDGE Q. HEALTHCARE ETHICS 458 (1996)CrossRefGoogle ScholarPubMed (discussing the ethical issues). In resolving malpractice claims, courts generally hold interns and residents to the same standard of care as more experienced physicians. See McBride v. United States, 462 F.2d 72, 74 (9th Cir. 1972); St. Germain v. Pfeifer, 637 N.E.2d 848, 852-53 (Mass. 1994); Baccari v. Donat, 741 A.2d 262, 264 (R.I. 1999).

81 See Gaston v. Hunter, 588 P.2d 326, 351 (Ariz. Ct. App. 1978) (“[T]he fact that Dr. Hunter had limited experience with the procedure and was not an authorized investigator of chymopapain would be relevant to plaintiff's informed consent to the operation.”); id. at 351 n.26 (“In the case of a new or unusual procedure, the individual physician's experience and ‘track record’ would seem even more important than when an established, common procedure is contemplated.”); see also Wilson v. Scott, 412 S.W.2d 299, 301, 303 (Tex. 1967) (reversing summary judgment for defendant in a case where the plaintiff alleged that the physician had failed to disclose, among other things, “that he had not previously performed this operation” except on cadavers).

82 See, e.g., GA. CODE ANN. § 43-34-68 (Supp. 2001) (acupuncture); MINN. STAT. ANN. § 147B.06(1)(b) (1998) (acupuncture); N.J. STAT. ANN. § 24:6F-1 (2000) (laetrile); WASH. REV. CODE ANN. § 70.54.190 (1992) (dimethyl sulfoxide (DMSO)); W. VA. CODE § 16-5A-9a (2001) (laetrile).In addition, physicians may face sanctions if they provide experimental therapy without consent. See, e.g., Clark v. Department of Prof. Reg., Bd. of Med. Examiners, 463 So. 2d 328, 333 (Fla. Ct. App. 1985); see also State Bd. of Med. Examiners v. Burzynski, 917 S.W.2d 365, 367-70 (Tex. Ct. App. 1996) (upholding the imposition of sanctions against a physician who had treated cancer patients with drugs not approved by the FDA).

83 CAL. HEALTH & SAFETY CODE §§ 24170-24179 (1992); see also FLA. STAT. ANN. § 381.026(4)(e) (2001); N.Y. PUB. HEALTH LAW §§ 2440-2446 (2002); VA. CODE ANN. § 32.1-162.16 to .20 (2001); Hecht v. Kaplan, 645 N.Y.S.2d 51, 53 (App. Div. 1996) (rejecting the plaintiff's claim that the decision to perform an additional diagnostic test on a sample of her blood amounted to experimentation without consent in violation of the state statute); T.D. v. N.Y. State Office of Mental Health, 626 N.Y.S.2d 1015, 1021-23 (Sup. Ct. 1995) (holding that state regulations authorizing research on psychiatric patients conflicted with the New York statute); Woltjen, Maria, Note, Regulation of Informed Consent to Human Experimentation, 17 LOY. U. CHI. L.J. 507, 518-23 (1986)Google Scholar (surveying state statutes).

84 Compare Daum v. SpineCare Med. Group, Inc., 61 Cal. Rptr. 2d 260, 271-73 (Ct. App. 1997) (explaining that the state statute along with federal requirements exceeded the common law duty to secure informed consent for experimental therapies, and holding that the plaintiff could assert a negligence per se claim against the defendants for failing to inform him of the investigational status of a spinal fixation device), with Trantafello v. Med. Ctr. of Tarzana, 227 Cal. Rptr. 84, 87 & n.2 (Ct. App. 1986) (rejecting the plaintiff's argument that a surgeon who allegedly used an innovative procedure had violated the statute's “extremely detailed” consent requirements because it only “deals with experiments on human subjects in the course of pure research”).

85 See Jane L. v. Bangerter, 61 F.3d 1493, 1500-02 (10th Cir. 1995), rev’d on other grds., 518 U.S. 137 (1996); Margaret S. v. Edwards, 794 F.2d 994, 999 (5th Cir. 1986) (“The whole distinction between experimentation and testing, or between research and practice is … almost meaningless in the medical context.”); Lifechez v. Hartigan, 735 F. Supp. 1361, 1364-66 (N.D. Ill.), aff’d mem., 914 F.2d 260 (7th Cir. 1990).

86 See, e.g., Moore v. Baker, 989 F.2d 1129, 1133 (11th Cir. 1993); Schiff v. Prados, 112 Cal. Rptr. 2d 171, 182-84 (Ct. App. 2001); see also Cleary v. Group Health Ass’n, 691 A.2d 148 (D.C. 1997) (rejecting a claim that, in describing options available to a patient, his physicians negligently interpreted published studies about an experimental surgical procedure); Prillaman, Hunter L., A Physician's Duty to Inform of Newly Developed Therapy, 6 J. CONTEMP. HEALTH L. & POL’Y 43, 52-58 (1990)Google ScholarPubMed (discussing the difficulty that arises in deciding whether an alternative medical treatment is sufficiently accepted so that it must be disclosed); cf. Christopher K. Daugherty, Commentary, HASTINGS CTR. REP., Sept.-Oct. 1996, at 20, 21 (arguing that physicians should tell their patients about the availability of a clinical trial).

87 See, e.g., Miller v. Whitburn, 10 F.3d 1315, 1320 (7th Cir. 1993); Holder v. Prudential Ins. Co., 951 F.2d 89, 90-91 (5th Cir. 1992); Goodman v. Sullivan, 891 F.2d 449, 451 (2d Cir. 1989); Weaver v. Reagan, 886 F.2d 194, 198-99 (8th Cir. 1989); see also Hoffman, Sharona, A Proposal for Federal Legislation to Address Health Insurance Coverage for Experimental and Investigational Treatments, 78 OR. L. REV. 203, 220 (1999)Google Scholar; Holder, Angela R., Funding Innovative Medical Treatment, 57 ALB. L. REV. 795, 795-805 (1994)Google ScholarPubMed; James, Frank P., Comment, The Experimental Treatment Exclusion Clause: A Tool for Silent Rationing of Health Care?, 12 J. LEGAL MED. 359, 418 (1991)CrossRefGoogle ScholarPubMed; Lahr, J. Gregory, Comment, What Is the Method to Their “Madness”? Experimental Treatment Exclusions in Health Insurance Policies, 13 J. CONTEMP. HEALTH L. & POL’Y 613, 623-33 (1997)Google ScholarPubMed; cf. Schumake v. Travelers Ins. Co., 383 N.W.2d 259, 264 (Mich. Ct. App. 1985) (“[S]ince medicine is an evolving science in which treatments are at one time regarded as valid and later discredited, we hold that a decision as to necessity shall be reviewed in light of knowledge which existed at the time the [treatment] decision was rendered.”).

88 See Ferguson, John H. et al., Court-Ordered Reimbursement for Unproven Medical Technology: Circumventing Technology Assessment, 269 JAMA 2116, 2120 (1993)CrossRefGoogle ScholarPubMed; Hall, Mark A. & Anderson, Gerard F., Health Insurers’ Assessment of Medical Necessity, 140 U. PA. L. REV. 1637, 1637-41, 1649, 1655-56, 1678-80 (1992)CrossRefGoogle Scholar; Morreim, E. Haavi, From the Clinics to the Courts: The Role Evidence Should Play in Litigating Medical Care, 26 J. HEALTH POL. POL’Y & L. 409, 411-13 (2001)CrossRefGoogle ScholarPubMed (describing litigation over high-dose chemotherapy followed by autologous bone marrow transplant (HDC/ABMT) for breast cancer patients, which later proved to be ineffective); Saver, Richard S., Note, Reimbursing New Technologies: Why Are the Courts Judging Experimental Medicine?, 44 STAN. L. REV. 1095 (1992)CrossRefGoogle ScholarPubMed; see also Peters, William P. & Rogers, Mark C., Variation in Approval by Insurance Companies of Coverage for Autologous Bone Marrow Transplantation for Breast Cancer, 330 NEW ENG. J. MED. 473, 475-77 (1994)CrossRefGoogle ScholarPubMed.

89 See, e.g., Brook v. St. John's Hickey Mem. Hosp., 380 N.E.2d 72, 75-76 (Ind. 1978); see also Fiorentino v. Wenger, 227 N.E.2d 296, 300-01 (N.Y. 1967) (declining to hold a hospital liable for an independent physician's failure to secure informed consent for radical spinal surgery because the court feared that this might discourage the use of novel procedures).

90 See Doe v. Noe, 690 N.E.2d 1012, 1018 (Ill. App. Ct. 1997), vacated, 707 N.E.2d 588 (Ill. App. Ct. 1998); Faya v. Almaraz, 620 A.2d 327, 332 n.3, 333-34 (Md. 1993); see also Am. Bar Ass’n AIDS Coordinating Comm., Calming AIDS Phobia: Legal Implications of the Low Risk of Transmitting HIV in the Health Care Setting, 28 U. MICH. J.L. REFORM 733, 767-72 (1995)Google Scholar (recommending against a general duty to disclose); Zazzali, Mara E., Note, HIV-Infected Health Care Workers Who Perform Invasive, Exposure-Prone Procedures: Defining the Risk and Balancing the Interests of Health Care Workers and Patients, 28 SETON HALL L. REV. 1000, 1032-37 (1998)Google ScholarPubMed.

91 See Colton v. New York Hosp., 414 N.Y.S.2d 866, 876 (Sup. Ct. 1979); see also Sullivan v. O’Connor, 296 N.E.2d 183, 186 (Mass. 1973) (“Considering the uncertainties of medical science and the variations in the physical and psychological conditions of individual patients, doctors can seldom in good faith promise specific results.”); Sard v. Hardy, 379 A.2d 1014, 1026 (Md. 1977); cf. Schachar v. American Acad. Ophthalmology, Inc., 870 F.2d 397, 398-400 (7th Cir. 1989) (rejecting antitrust claim against medical society for characterizing radial keratotomy as “experimental”).

92 See Moore v. Regents of the Univ. of Cal., 793 P.2d 479, 483-86 (Cal. 1990); see also Kassirer, Jerome P., Financial Conflict of Interest: An Unresolved Ethical Frontier, 27 AM. J.L. & MED. 149 (2001)CrossRefGoogle ScholarPubMed; Miller, Frances H., Trusting Doctors: Tricky Business When It Comes to Clinical Research, 81 B.U. L. REV. 423, 431-43 (2001)Google Scholar. In Moore, however, the patient did not become an unwitting subject in a clinical trial, though he submitted to some follow-up testing that may have crossed the line; instead, after receiving treatment, his physicians preserved excised tissues for purposes of research and commercial gain. More generally, of course, physicians encounter all sorts of other potential conflicts of interest that do not have even an indirect connection to research activities. See Neade v. Portes, 739 N.E.2d 496, 501-05 (Ill. 2000); see also MARC A. RODWIN, MEDICINE, MONEY, AND MORALS: PHYSICIANS’ CONFLICTS OF INTEREST (1993); CONFLICTS OF INTEREST IN CLINICAL PRACTICE AND RESEARCH (Roy G. Spece, Jr. et al. eds., 1996); Bobinski, Mary Anne, Autonomy and Privacy: Protecting Patients from Their Physicians, 55 U. PITT. L. REV. 291, 301-09 (1994)Google ScholarPubMed; Shortell, Stephen M. et al., Physicians as Double Agents: Maintaining Trust in an Era of Multiple Accountabilities, 280 JAMA 1102 (1998)CrossRefGoogle Scholar.

93 See Whitlock v. Duke Univ., 637 F. Supp. 1463, 1468, 1470-72 (M.D.N.C. 1986) (reviewing claims based on brain damage allegedly caused by simulated deep dive experiments in a pressurized hyper-baric chamber, and concluding, based on guidance in the Nuremberg Code and federal regulations, that the degree of required risk disclosure is higher in the non-therapeutic context), aff’d, 829 F.2d 1340, 1343 (4th Cir. 1987); Vodopest v. MacGregor, 913 P.2d 779, 785, 789 (Wash. 1996) (declining to enforce an exculpatory clause in a case arising out of nontheraputic research); see also Smith v. United States, 412 F.2d 791, 793 (9th Cir. 1969) (Hufstedler, C.J., dissenting) (“[O]ne who subjects volunteers to nontherapeutic tests involving some risk of personal injury has, at a minimum, the duty fully to inform the volunteer about the tests and to secure his informed consent … .”); Bonner v. Moran, 126 F.2d 121, 123 (D.C. Cir. 1941); Halushka v. Univ. of Saskatchewan, 53 D.L.R.2d 436, 443-44 (Sask. Ct. App. 1965) (“[T]he duty imposed on those engaged in medical research … is at least as great as, if not greater than, the duty owed by the ordinary physician or surgeon to his patient.”).

94 See LARS NOAH & BARBARA A. NOAH, LAW, MEDICINE, AND MEDICAL TECHNOLOGY: CASES AND MATERIALS chs. 2 & 4 (2002).

95 See Noah, Lars, The Imperative to Warn: Disentangling the “Right to Know” from the “Need to Know” About Consumer Product Hazards, 11 YALE J. ON REG. 293, 331-32 (1994)Google Scholar. Although sometimes characterized as serving a patient disclosure function, the FDA's restrictions on prescription drug advertising directed to consumers primarily seek to prevent misleading promotional claims. See Noah, Lars, Advertising Prescription Drugs to Consumers: Assessing the Regulatory and Liability Issues, 32 GA. L. REV. 141, 176 (1997)Google Scholar (“[T]he FDA has not yet revised its advertising rules to require disclosures tailored to patients, and, even if it does, the FDA has not designed its disclosure requirements to fulfill a warning function (in contrast to PPIs for oral contraceptives) so much as to ensure that promotional claims do not lack fair balance.”).

96 See 49 Fed. Reg. 14,303, 14,327 (1984) (“The agency has not traditionally viewed making recommendations as to informed consent to be a proper function of prescription drug labeling. Unlike the case of investigational new drugs, the [statute] contains no express command that informed consent be obtained for approved uses of new drugs.”). Nonetheless, the FDA decided to do so in at least one case. See id. (“The ‘Warning’ section of oral hypoglycemic drug labeling will retain the statement that the patient should be informed of the potential risks and advantages of these drugs and of alternative modes of therapy.”); see also id. at 14,331 (codified at 21 C.F.R. § 310.517(b)).

97 See 21 C.F.R. § 130.45(d)(1) (1970); see also 21 C.F.R. § 310.501 (2001) (current version); Henley v. FDA, 77 F.3d 616, 618 (2d Cir. 1996) (describing the evolution of this PPI).

98 43 Fed. Reg. 4214, 4215 (1978) (“The physician, who by training and experience is best equipped to tailor discussion of drug therapy to the needs of individual patients, has the primary responsibility for advising patients about such information as directions for use, cautions against misuse, and warnings about possible adverse reactions.”).

99 See 42 Fed. Reg. 37,636, 37,637 (1977) (rejecting objections lodged by physicians); William J. Curran, Package Inserts for Patients: Informed Consent in the 1980s, 305 NEW ENG. J. MED. 1564, 1565 (1981) (“The protest against this proposal was immediate and strong in the medical profession … .”); see also Pharm. Mfrs. Ass’n v. FDA, 484 F. Supp. 1179, 1187-92 (D. Del.) (rejecting a challenge to the estrogen PPI premised in part on complaints that it inappropriately interfered with the doctor-patient relationship), aff’d, 634 F.2d 106 (3d Cir. 1980).

100 See 21 C.F.R. § 310.515 (2001) (estrogen); id. § 201.305(c) (isoproterenol inhalation preparations); Gardner, Marsha W., Increasing Patient Awareness in Drug Therapy: Ramifications of a Patient Package Insert Requirement, 66 GEO. L.J. 837 (1978)Google Scholar. In addition, manufacturers of childhood vaccines must distribute patient informed consent forms. See 42 U.S.C. § 300aa-26 (2000); 56 Fed. Reg. 51,798, 51,808 (1991); Mazur v. Merck & Co., 964 F.2d 1348, 1365-69 (3d Cir. 1992) (holding that a vaccine manufacturer satisfied its duty to warn by delegating to the Centers for Disease Control and Prevention the responsibility for disseminating patient labeling).

101 See 44 Fed. Reg. 40,016, 40,020 (1979) (concluding that “oral communication of information about prescription drug products … cannot be relied upon to provide patients with the information they need to use prescription drug products properly”); id. at 40,022-24 (rejecting objections from physicians and industry); see also Gilhooley, Margaret, Learned Intermediaries, Prescription Drugs, and Patient Information, 30 ST. LOUIS U. L.J. 633, 668-69 (1986)Google Scholar (noting that many physicians failed to communicate risk information about drugs to patients).

102 See 45 Fed. Reg. 60,754, 60,773 (1980).

103 See 47 Fed. Reg. 39,147, 39,148 (1982) (noting also “the strong disagreement about the design and value of the program on the part of the health professionals who would have to implement it”); 46 Fed. Reg. 23,739, 23,815 (1981); see also Public Citizen v. HHS, 671 F.2d 518 (D.C. Cir. 1981) (reviewing a procedural challenge to the stay); Kendellen, Rosalind M., The Food and Drug Administration Retreats from Patient Package Inserts for Prescription Drugs, 40 FOOD DRUG COSM. L.J. 172, 178-87 (1985)Google Scholar.

104 See Kessler, David A., Communicating with Patients About Their Medications, 325 NEW ENG. J. MED. 1650, 1650-51 (1991)CrossRefGoogle ScholarPubMed; Rowe, Howard M., Patient Package Inserts: The Proper Prescription?, 50 FOOD & DRUG L.J. 95 (1995)Google ScholarPubMed; see also Katz, Jeffrey N. et al., Informed Consent and the Prescription of Nonsteroidal Antiinflammatory Drugs, 35 ARTHRITIS & RHEUMATISM 1257, 1261-62 (1992)CrossRefGoogle ScholarPubMed (finding limited disclosure by physicians of NSAID side effects, and recommending efficient methods of communication such as pamphlets); cf. Brian Reid, Rx for the Future: Get an Ix, WASH. POST, June 25, 2002, at Z1 (discussing efforts to encourage physicians to guide patients toward informative web sites).

105 See 60 Fed. Reg. 44,182, 44,191-93 (1995) (discussing patients’ desire for more information concerning side effects than most physicians provide); see also Paytash, Catherine A., Note, The Learned Intermediary Doctrine and Patient Package Inserts: A Balanced Approach to Preventing Drug-Related Injuries, 51 STAN. L. REV. 1343, 1371 (1999)CrossRefGoogle Scholar (“An FDA-mandated system of PPIs for all prescription drugs is far preferable to a host of voluntary efforts on the part of various organizations.”).

106 See Pub. L. No. 104-180, § 601, 110 Stat. 1569, 1593 (1996); see also 63 Fed. Reg. 66,378, 66,396-98 (1998) (codified at 21 C.F.R. pt. 208 (2001)); Marwick, Charles, MedGuide: At Last a Long-Sought Opportunity for Patient Education About Prescription Drugs, 277 JAMA 949 (1997)CrossRefGoogle Scholar; Francesca Lunzer Kritz, Not-So-Fine Print: Patient Drug Leaflets Omit Key Warnings, Other Information, WASH. POST, Aug. 13, 2002, at Z1 (describing problems in the implementation of the voluntary PPI program); Sheryl Gay Stolberg, Faulty Warning Labels Add to Risk in Prescription Drugs, N.Y. TIMES, June 4, 1999, at A27 (describing inadequacies in the voluntary efforts and the FDA's resulting initiative to require PPIs for ten risky new drugs each year).

107 See Plant, Nancy K., The Learned Intermediary Doctrine: Some New Medicine for an Old Ailment, 81 IOWA L. REV. 1007, 1034 & n.131 (1996)Google Scholar (reporting that the FDA has done so for more than 30 products). For instance, the agency evidently required PPIs when it approved prescription nicotine patches. See Edwards v. Basel, 933 P.2d 298, 299-300, 301 (Okla. 1997). Pharmaceutical manufacturers sometimes voluntarily provide separate information for patients. See, e.g., Polley v. Ciba-Geigy Corp., 658 F. Supp. 420, 421-22 (D. Alaska 1987); Presto v. Sandoz Pharm. Corp., 487 S.E.2d 70, 73-74 (Ga. Ct. App. 1997).

108 See Stern, Robert S., When a Uniquely Effective Drug Is Teratogenic: The Case of Isotretinoin, 320 NEW ENG. J. MED. 1007, 1008 (1989)CrossRefGoogle ScholarPubMed (noting that, in order to curb prescribing in women who may become pregnant, the manufacturer added “a structuring of the consent process that is probably more elaborate than that used with any other oral drug”); Krause, Joan H., Accutane: Has Drug Regulation in the United States Reached Its Limits?, 6 J.L. & HEALTH 1, 19-20 (1991)Google Scholar; Diane Knich, Acne Drug Safeguards, WASH. POST, Apr. 9, 2002, at Z1 (noting that over the last two decades, in spite of label warnings, more than 2,000 women became pregnant while taking the drug, which prompted the FDA to impose stringent distribution restrictions and informed consent requirements).

109 See Noah, Lars, A Miscarriage in the Drug Approval Process? Mifepristone Embroils the FDA in Abortion Politics, 36 WAKE FOREST L. REV. 571, 585-86 (2001)Google Scholar; Gina Kolata, U.S. Approves Abortion Pill, N.Y. TIMES, Sept. 29, 2000, at A1 (“A woman will be given written instructions … , and her doctor must sign a statement saying they have read the instructions and will comply with them exactly. The woman must also agree to have a surgical abortion if the pills do not succeed.”).

110 See Gilhooley, Margaret, When Drugs Are Safe for Some but Not Others: The FDA Experience and Alternatives for Products Liability, 36 HOUS. L. REV. 927, 943-44 (1999)Google Scholar; Jamie Talan, Thalidomide's Legacy, WASH. POST, Jan. 4, 2000, at Z10 (reporting that physicians who prescribe the drug receive an “education kit, including a consent form to be signed by both doctor and patient”); see also 56 Fed. Reg. 49,098 (1991) (urging manufacturers of silicone-gel breast implants to provide physicians with risk disclosure forms for patients); Rebecca S. Dresser et al., Breast Implants Revisited: Beyond Science on Trial, 1997 WIS. L. REV. 705, 715-21 (evaluating this initiative).

111 See Annas, George J., Mengele's Birthmark: The Nuremberg Code in United States Courts, 7 J. CONTEMP. HEALTH L. & POL’Y 17, 18-22 (1991)Google ScholarPubMed; Katz, Jay, Human Sacrifice and Human Experimentation: Reflections at Nuremberg, 22 YALE J. INT’L L. 401, 405-07 (1997)Google Scholar.

112 See JONATHAN D. MORENO, UNDUE RISK: SECRET STATE EXPERIMENTS ON HUMANS (1999); Palmer, Larry I., Paying for Suffering: The Problem of Human Experimentation, 56 MD. L. REV. 604 (1997)Google Scholar; see also United States v. Stanley, 483 U.S. 669, 686-89 (1987) (Brennan, J., concurring in part and dissenting in part) (criticizing the Army's secret LSD experiments); Heinrich v. Sweet, 62 F. Supp. 2d 282 (D. Mass. 1999) (boron neutron capture therapy); In re Cincinnati Radiation Litig., 874 F. Supp. 796, 800-05 (S.D. Ohio 1995); Barrett v. United States, 660 F. Supp. 1291, 1299 (S.D.N.Y. 1987) (Army testing of mescaline-derivatives as potential chemical warfare agents on mental hospital patients without their consent); Beecher, Henry K., Ethics and Clinical Research, 274 NEW ENG. J. MED. 1354 (1966)CrossRefGoogle ScholarPubMed (discussing twenty-two examples of research studies conducted without consent of the subjects); Curran, William J., The Tuskegee Syphilis Study, 289 NEW ENG. J. MED. 730 (1973)CrossRefGoogle ScholarPubMed; Pappworth, M.H., “Human Guinea Pigs”—A History, 301 BRIT. MED. J. 1456 (1990)CrossRefGoogle ScholarPubMed.

113 Although it was only one of ten principles enunciated in the Nuremberg Code, consent received top billing:

The Nuremberg Code (1947), 276 JAMA 1691 (1996)CrossRefGoogle Scholar; see also THE NAZI DOCTORS AND THE NUREMBERG CODE: HUMAN RIGHTS IN HUMAN EXPERIMENTATION (George J. Annas & Michael A. Grodin eds., 1992); Shuster, Evelyne, Fifty Years Later: The Significance of the Nuremberg Code, 337 NEW ENG. J. MED. 1436, 1439 (1997)CrossRefGoogle ScholarPubMed. More so than the informed consent doctrine in tort law, these guidelines appear to emphasize a subjective inquiry into comprehension rather than an objective standard preoccupied with the adequacy of disclosure.

114 See Emanuel, Ezekiel J. et al., What Makes Clinical Research Ethical?, 283 JAMA 2701, 2701-02 (2000)CrossRefGoogle ScholarPubMed (noting “the near obsession with autonomy in US bioethics,” but cautioning that the Nuremberg Code and other ethical guidelines “were written in response to specific events” and therefore “tend to emphasize certain ethical requirements while eliding others”).

115 See 39 Fed. Reg. 18,914 (1974) (codified as amended at 45 C.F.R. pt. 46).

116 See 45 C.F.R. § 46.103 (2001) (requiring that all institutions receiving federal funds provide the government with an “assurance” that all research conducted at the institution, regardless of the source of funding, will protect human subjects according to the principles in the regulations).

117 See 46 Fed. Reg. 8942 (1981) (codified as amended at 21 C.F.R. pts. 50 & 56). Fifteen years earlier, the FDA had issued a policy statement calling for informed consent in clinical trials of regulated products. See 31 Fed. Reg. 11,415 (1966); see also 56 Fed. Reg. 28,003 (1991) (extending the HHS rules to the research activities supported by other federal agencies); Snyderman, Ralph & Holmes, Edward W., Oversight Mechanisms for Clinical Research, 287 SCIENCE 595, 597 (2000)CrossRefGoogle ScholarPubMed (criticizing redundancies and ambiguities in the federal rules).

118 See 21 C.F.R. §§ 50.20, 56.109(b)&(c), 56.111(a)(4)&(5); 45 C.F.R. §§ 46.109(b)&(c), 46.111(a)(4)&(5); see also Moore, Dale L., An IRB Member's Perspective on Access to Innovative Therapy, 57 ALB. L. REV. 559, 566-68 (1994)Google ScholarPubMed; Nightingale, Stuart L., Challenges in Human Subject Protection, 50 FOOD & DRUG L.J. 493 (1995)Google ScholarPubMed.

119 See 21 C.F.R. § 50.27; 45 C.F.R. § 46.117(a).

120 21 C.F.R. § 50.25(a)(1); 45 C.F.R. § 46.116(a)(1).

121 See Hammerschmidt, Dale E. & Keane, Moira A., Institutional Review Board (IRB) Review Lacks Impact on the Readability of Consent Forms for Research, 304 AM. J. MED. SCI. 348, 350 (1992)CrossRefGoogle ScholarPubMed; Katz, Jay, Human Experimentation and Human Rights, 38 ST. LOUIS U. L.J. 7, 36 (1993)Google ScholarPubMed (“[C]urrent informed consent forms often provide IRBs rather than the subjects with a better understanding of investigators’ intentions.”). It also may reflect the need for achieving uniformity so as to minimize inter-subject variation in response to treatment or placebo. See Brownell, Kelly D. & Stunkard, Albert J., The Double-Blind in Danger: Untoward Consequences of Informed Consent, 139 AM. J. PSYCHIATRY 1487, 1488-89 (1982)Google ScholarPubMed; Margaret Talbot, The Placebo Prescription, N.Y. TIMES MAG., Jan. 9, 2000, at 34. Some have recommended using innovative consent forms designed to test subject comprehension. See Miller, Robert & Willner, Henry S., The Two-Part Consent Form: A Suggestion for Promoting Free and Informed Consent, 290 NEW ENG. J. MED. 964, 965 (1974)CrossRefGoogle ScholarPubMed (proposing to append a questionnaire).

122 See BERG ET AL., supra note 7, at 259 (recognizing the risk of becoming “complacent”); Annas, George J., Death and the Magic Machine: Informed Consent to the Artificial Heart, 9 W. NEW ENG. L. REV. 89, 91 (1987)Google ScholarPubMed (warning that “informed consent can be used improperly as an excuse to justify massive assaults on the welfare of human subjects, even though the quality of the consent is highly questionable, and the quality of the experiment itself does not meet the welfare requirements of the Nuremberg Code”); id. at 99 (emphasizing that “informed consent alone is an insufficient justification for radical human experimentation,” and calling for “[p]roper attention to the other nine precepts of the Nuremberg Code” about the nature of the research that one must satisfy before seeking consent); Emanuel et al., supra note 114, at 2701 (“What makes research involving human subjects ethical? Informed consent is the answer most … [IRB] members would probably offer… . [O]btaining informed consent does not ensure ethical research … .”); Truog, Robert D. et al., Is Informed Consent Always Necessary for Randomized, Controlled Trials?, 340 NEW ENG. J. MED. 804, 806 (1999)CrossRefGoogle ScholarPubMed (“The most effective protection against exploitation comes not from the process of informed consent but, rather, from careful oversight and scrutiny of conscientious [IRBs]. Boards that approve questionable studies on the assumption that the informed-consent process will protect research subjects against abuse abrogate their responsibility … .”); see also Baram, Michael, Making Clinical Trials Safer for Human Subjects, 27 AM. J.L. & MED. 253, 282 (2001)CrossRefGoogle ScholarPubMed; Moreno, Jonathan et al., Updating Protections for Human Subjects Involved in Research, 280 JAMA 1951, 1955 (1998)CrossRefGoogle ScholarPubMed (“[A]n emphasis on paper compliance is only appropriate insofar as it tends to support the IRB system's true goal: the protection of human subjects.”). But cf. Ellis, Gary B., Editorial, Keeping Research Subjects out of Harm's Way, 282 JAMA 1963, 1964 (1999)CrossRefGoogle ScholarPubMed (defending against charges that federal regulations impose “inappropriately bureaucratic” requirements, and emphasizing the role of IRBs in “review[ing] the informed consent process and its signal feature, the informed consent document”).

123 See BERG ET AL., supra note 7, at 286 (“IRB approval permits the research to be undertaken on the condition that individual subjects agree to participate.”); Capron, supra note 7, at 374-75; Edgar, Harold & Rothman, David J., The Institutional Review Board and Beyond: Future Challenges to the Ethics of Human Experimentation, 73 MILBANK Q. 489, 493, 498 (1995)CrossRefGoogle ScholarPubMed; Meisel & Roth, supra note 13, at 332; see also PAUL M. MCNEILL, THE ETHICS AND POLITICS OF HUMAN EXPERIMENTATION 145 (1993).

124 See Calabresi, Guido, Reflections on Medical Experimentation in Humans, 98 DAEDALUS 387, 391, 404-05 (1969)Google Scholar (questioning the value of informed consent requirements in research, and arguing in favor of more direct supervision); Lawrence R. Tancredi, Informed Consent: The Dilemma, in BIOMEDICAL INNOVATION 301, 304 (Edward B. Roberts et al. eds., 1981) (“Some treatments may be at such a primitive stage of development that … the information is so insubstantial that, even though the patient may have been apprised of all information available and may have voluntarily and competently agreed to the experiment, an informed consent is precluded.”); see also Beecher, Henry K., Consent in Clinical Experimentation: Myth and Reality, 195 JAMA 34 (1966)CrossRefGoogle Scholar; F.J. Ingelfinger, Editorial, Informed (but Uneducated) Consent, 287 NEW ENG. J. MED. 465 (1972); Taylor, Kathryn M. & Kelner, Merrijoy, Informed Consent: The Physicians’ Perspective, 24 SOC. SCI. & MED. 135, 142 (1987)CrossRefGoogle ScholarPubMed.

125 See Goldstein, Adam O. et al., Consent Form Readability in University-Sponsored Research, 42 J. FAM. PRACTICE 606, 609-11 (1996)Google ScholarPubMed; Grossman, Stuart A. et al., Are Informed Consent Forms that Describe Clinical Oncology Research Protocols Readable by Most Patients and Their Families?, 12 J. CLINICAL ONCOLOGY 2211, 2212-14 (1994)CrossRefGoogle ScholarPubMed; Featherstone, Katie & Donovan, Jenny L., Random Allocation or Allocation at Random? Patients’ Perspectives of Participation in a Randomised Controlled Trial, 317 BRIT. MED. J. 1177, 1179 (1998)CrossRefGoogle ScholarPubMed; Joffe, Steven et al., Quality of Informed Consent in Cancer Clinical Trials: A Cross-Sectional Survey, 358 LANCET 1772, 1776 (2001)CrossRefGoogle ScholarPubMed; Laura C. McBride & Mark R. Yessian, IRBs and Continuing Review: Regulatory Interference or Vital Safeguard?, FOOD DRUG COSM. & MED. DEV. L. DIG., Mar. 1999, at 13 (describing a 1995 survey of 371 research subjects finding that nearly twenty percent of those questioned incorrectly believed that they were not and never had been research subjects); Meisel & Roth, supra note 13, at 304-06, 314; Schultz, Amelia L. et al., Are Research Subjects Really Informed?, 123 W. J. MED. 76 (1975)Google ScholarPubMed; Tarnowski, Kenneth J. et al., Readability of Pediatric Biomedical Research Informed Consent Forms, 85 PEDIATRICS 58, 61 (1990)Google ScholarPubMed; see also Barbour, Galen L. & Blumenkrantz, Michael J., Videotape Aids Informed Consent Decision, 240 JAMA 2741, 2742 (1978)CrossRefGoogle ScholarPubMed; Bjørn, Else et al., Can the Written Information to Research Subjects Be Improved?—An Empirical Study, 25 J. MED. ETHICS 263, 266 (1999)CrossRefGoogle ScholarPubMed; Edwards, Sarah J.L. et al., Informed Consent for Clinical Trials: In Search of the “Best” Method, 47 SOC. SCI. & MED. 1825, 1839 (1998)CrossRefGoogle ScholarPubMed; Epstein, Lynn Chaikin & Lasagna, Louis, Obtaining Informed Consent: Form or Substance, 123 ARCHIVES INTERNAL MED. 682, 684-86 (1969)CrossRefGoogle ScholarPubMed (finding an inverse correlation between detail and comprehension). See generally Council on Scientific Affairs, Health Literacy, 281 JAMA 552 (1999)CrossRefGoogle Scholar.

126 See Paul S. Appelbaum et al., False Hopes and Best Data: Consent to Research and the Therapeutic Misconception, HASTINGS CTR. REP., Apr. 1987, at 20, 21-22 ; Nancy E. Kass et al., Trust: The Fragile Foundation of Contemporary Biomedical Research, HASTINGS CTR. REP., Sept.- Oct. 1996, at 25, 28; Schaeffer, Monica H. et al., The Impact of Disease Severity on the Informed Consent Process in Clinical Research, 100 AM. J. MED. 261, 266-67 (1996)CrossRefGoogle ScholarPubMed; Advisory Committee on Human Radiation Experiments, Research Ethics and the Medical Profession, 276 JAMA 403, 408 (1996)CrossRefGoogle Scholar; see also Hewlett, Sarah, Consent to Clinical Research—Adequately Voluntary or Substantially Influenced?, 22 J. MED. ETHICS 232 (1996)CrossRefGoogle ScholarPubMed; Lawrence K. Altman, The Ordeal of a “Human Experiment”, N.Y. TIMES, May 14, 1985, at C3 (describing the desperation of patients who signed seventeen page long informed consent forms without reading them in order to receive artificial hearts).

127 See Daugherty, Christopher et al., Perceptions of Cancer Patients and Their Physicians Involved in Phase I Trials, 13 J. CLINICAL ONCOLOGY 1062, 1067 (1995)CrossRefGoogle ScholarPubMed; see also Edwards, Sarah J.L. et al., The Ethics of Randomised Controlled Trials from the Perspectives of Patients, the Public, and Healthcare Professionals, 317 BRIT. MED. J. 1209 (1998)CrossRefGoogle ScholarPubMed. Even so, subjects enrolled in clinical trials, whether they receive the experimental treatment or a placebo control, seem to enjoy better outcomes than patients with the same condition who receive treatment from physicians. See Lantos, John D., Editorial, The “Inclusion Benefit” in Clinical Trials, 134 J. PEDIATRICS 130, 130 (1999)CrossRefGoogle ScholarPubMed (“A number of explanations have been offered for the apparent benefit of RCT participation, including selection bias, placebo effects, and adherence to well-defined protocols [for other aspects of disease management].”); Shankar Vedantam, Against Depression, a Sugar Pill Is Hard to Beat, WASH. POST, May 7, 2002, at A1. Nonetheless, patients in the experimental arm of a clinical trial sometimes suffer serious side effects. See, e.g., Lawrence K. Altman, Fatal Drug Trial Raises Questions About “Informed Consent”, N.Y. TIMES, Oct. 5, 1993, at C3.

128 See Dickert, Neal & Grady, Christine, What's the Price of a Research Subject? Approaches to Payment for Research Participation, 341 NEW ENG. J. MED. 198 (1999)CrossRefGoogle Scholar (discussing the relative merits of the market model, the wage-payment model, and the reimbursement model for compensating research subjects, and concluding that the wage-payment model most effectively reduces concerns about inappropriate inducement).

129 See Dahl v. HEM Pharm. Corp., 7 F.3d 1399, 1404-05 (9th Cir. 1993) (affirming a preliminary injunction requiring the sponsor to continue supplying an investigational AIDS drug); Macklin, Ruth, The Ethical Problems with Sham Surgery in Clinical Research, 341 NEW ENG. J. MED. 992, 994 (1999)CrossRefGoogle ScholarPubMed.

130 See 21 C.F.R. §§ 56.115-.124; 45 C.F.R. §§ 46.115(b), 46.123; see also Gina Kolata, Johns Hopkins Death Brings Halt to U.S.-Financed Human Studies, N.Y. TIMES, July 20, 2001, at A1; Sheryl Gay Stolberg, Committee Considers Change in Reporting on Gene Therapies, N.Y. TIMES, Dec. 11, 1999, at A13; Rick Weiss & Deborah Nelson, Gene Therapy's Troubling Crossroads, WASH. POST, Dec. 31, 1999, at A3.

131 See GENERAL ACCOUNTING OFFICE, SCIENTIFIC RESEARCH: CONTINUED VIGILANCE CRITICAL TO PROTECTING HUMAN SUBJECTS, HEHS-96-72, at 11-16 (1996); OFFICE OF THE INSPECTOR GENERAL, HHS, INSTITUTIONAL REVIEW BOARDS: THEIR ROLE IN REVIEWING APPROVED RESEARCH, OEI-01-97-00190 (1998); George J. Annas, Regs Ignored in Research, NAT’L L.J., Nov. 15, 1999, at A20 (referencing a review of 1,000 spot-checks conducted by the FDA which found that 213 researchers had failed to obtain informed consent from subjects); Cohen, Jon, Clinical Trial Monitoring: Hit or Miss?, 264 SCIENCE 1534, 1536 (1994)CrossRefGoogle ScholarPubMed (explaining that, in over 3,000 IRB site inspections, the FDA found informed consent problems at over half of the inspected sites); Epstein, Keith & Sloat, Bill, Letter, Informed Consent Is Not Always Obtained in United States, 315 BRIT. MED. J. 249, 249 (1997)Google Scholar; Hoffman, Sharona, Continued Concern: Human Subject Protection, the Institutional Review Board, and Continuing Review, 68 TENN. L. REV. 725, 734-35 (2001)Google ScholarPubMed; Kelsey, Frances O., The FDA's Enforcement of IRBs and Patient Informed Consent, 44 FOOD DRUG COSM. L.J. 13, 18-19 (1989)Google ScholarPubMed; Morse, Michael A. et al., Monitoring and Ensuring Safety During Clinical Research, 285 JAMA 1201 (2001)CrossRefGoogle ScholarPubMed; Philip J. Hilts, Researchers Admit Study with Drugs Had No O.K., N.Y. TIMES, Oct. 28, 1993, at B5.

132 See 21 C.F.R. § 50.25(c); 45 C.F.R. § 46.116(e); see also 21 C.F.R. § 50.20 (prohibiting the use of “exculpatory language” purporting to release any parties “from liability for negligence”); 45 C.F.R. § 46.116 (same).

133 See Kus v. Sherman Hosp., 644 N.E.2d 1214, 1220-21 (Ill. App. Ct. 1995) (allowing medical battery claim to proceed against hospital where physician implanted a pair of investigational intraocular lenses using a consent form that deviated from the one approved by the IRB “so that [plaintiff] allegedly did not know that he was participating in an experiment”); Grimes v. Kennedy Krieger Inst., 782 A.2d 807, 813 (Md. 2001) (discussing negligent oversight of a study to compare different methods of lead paint abatement in housing occupied by children); Friter v. Iolab Corp., 607 A.2d 1111, 1113 (Pa. Super. Ct. 1992) (holding that, where a patient who received an investigational intraocular lens implant was never informed that the device was experimental or that his treatment was being delivered under the auspices of a research protocol, “the hospital, as a participant in a clinical investigation … specifically assumed a duty to ensure that informed consent was obtained by any patient participating in the study”); Barbara A. Noah, Bioethical Malpractice: Risk and Responsibility in Human Research (forthcoming 2003).

134 See ALBERT R. JONSEN ET AL., CLINICAL ETHICS 192 (4th ed. 1998) (“Clinical research is defined as any clinical intervention involving human subjects, patients or normal volunteers, performed in accord with a protocol designed to yield generalizable scientific knowledge.”); Annas, George J., Questing for Grails: Duplicity, Betrayal and Self-Deception in Postmodern Medical Research, 12 J. CONTEMP. HEALTH L. & POL’Y 297, 323 (1996)Google ScholarPubMed (“Research is research, designed to test a hypothesis and performed based on the rules of the protocol; treatment is something else, designed to benefit a patient, and subject to change whenever change is seen in the patient's best interest.”); Churchill, Larry R. et al., Genetic Research as Therapy: Implications of “Gene Therapy” for Informed Consent, 26 J.L. MED. & ETHICS 38 (1998)CrossRefGoogle ScholarPubMed.

135 See Hellman, Samuel & Hellman, Deborah S., Of Mice but Not Men: Problems of the Randomized Clinical Trial, 324 NEW ENG. J. MED. 1585, 1585 (1991)CrossRefGoogle Scholar (“Researchers using a randomized clinical trial can be described as physician-scientists, a term that expresses the tension between the two roles.”); Katz, supra note 121, at 11-12, 15-16 (“Individual patient-centered therapy gives way to a collective patient-centered endeavor in which the abstraction of the research question tends to objectify the person-patient.”); id. at 17 (“[A] major problem which compromises the protection afforded to subjects of research resides in the obfuscation of the boundaries between clinical research and clinical practice.”); id. at 18 (warning that, in clinical research settings, “physician-investigators have dual allegiances—to their patient-subjects and the research protocol”); id. at 28 (“In conflating clinical trials and therapy, as well as patients and subjects, as if both were one and the same, physician-investigators unwittingly become double agents with conflicting loyalties.”); id. at 33 (“The commitment to objectivity invites investigators’ thought processes to become objectified and, in turn, to transform the human beings who are the subjects of research into data points to be plotted on a chart that will prove or disprove a research hypothesis.”); Levine, Robert J., Clinical Trials and Physicians as Double Agents, 65 YALE J. BIOL. & MED. 65 (1992)Google ScholarPubMed; see also Annas, George J., The Changing Landscape of Human Experimentation: Nuremberg, Helsinki, and Beyond, 2 HEALTH MATRIX 119, 130-31, 135 (1992)Google ScholarPubMed (discussing the dual roles, and proposing enhanced rules governing research “that would not necessarily apply to treatment in a doctor-patient relationship untainted by conflicts of interest”).

136 National Research Act, Pub. L. No. 93-348, § 202(a)(1)(B)(i), 88 Stat. 342, 349 (1974).

137 44 Fed. Reg. 23,192, 23,193 (1979); see also id. (“Research and practice may be carried on together when research is designed to evaluate the safety and efficacy of a therapy. This need not cause any confusion regarding whether or not the activity requires review; the general rule is that if there is any element of research in an activity, that activity should undergo review for the protection of human subjects.”); id. at 23,195 (“[T]he extent and nature of information should be such that persons, knowing that the procedure is neither necessary for their care nor perhaps fully understood, can decide whether they wish to participate in the furthering of knowledge.”). The FDA borrowed from this guidance in the course of developing its informed consent rules. See 44 Fed. Reg. 47,713, 47,716 (1979).

138 A few years later, the Commission's successor conflated the two, concluding that informed consent requirements in research and treatment had become “basically the same.” See PRESIDENT's COMMISSION FOR THE STUDY OF ETHICAL PROBLEMS IN MEDICINE AND BIOMEDICAL AND BEHAVIORAL RESEARCH, MAKING HEALTH CARE DECISIONS: A REPORT ON THE ETHICAL AND LEGAL IMPLICATIONS OF INFORMED CONSENT IN THE PATIENT-PRACTITIONER RELATIONSHIP 1 n.1, 21 n.19 (1982); see also Katz, Jay, Limping Is No Sin: Reflections on Making Health Care Decisions, 6 CARDOZO L. REV. 243 (1984)Google ScholarPubMed (commenting on the work of the President's Commission). A report from the latest incarnation of this group again emphasized the importance of informed consent but criticized the preoccupation with getting subjects to sign forms. See Nat’l Bioethics Advisory Com’n, Ethical and Policy Issues in Research Involving Human Participants, Aug. 2001, available at http://bioethics.georgetown.edu/nbac/pubs.html (last visited Oct. 26, 2002).

139 See Goldner, Jesse A., An Overview of Legal Controls on Human Experimentation and the Regulatory Implications of Taking Professor Katz Seriously, 38 ST. LOUIS U. L.J. 63, 113-14 (1993)Google ScholarPubMed (uncritically accepting this test).

140 See Annas, supra note 134, at 313 (“It is the nature of the intervention and the data that support its use, not … the intent of the physician-researcher, that determine the nature of the intervention.”); id. at 314-16; Nancy M.P. King, Experimental Treatment: Oxymoron or Aspiration?, HASTINGS CTR. REP., July-Aug. 1995, at 6, 9, 11-14; see also Pellegrino, Edmund D., Autonomy, Beneficence, and the Experimental Subject's Consent: A Response to Jay Katz, 38 ST. LOUIS U. L.J. 55, 61 (1993)Google ScholarPubMed (“Informed consent … applies equally in the therapeutic and the experimental situation, and it is the responsibility of every physician.”).

141 See Annas, supra note 134, at 316.

Id. at 322; see also id. at 321 (“There is, of course, a continuum from (scientific) experiment to (therapeutic) treatment, but few interventions are in the gray zone and an objective distinction can almost always be made between an experimental intervention and a treatment.” (footnote omitted)).

142 See 21 U.S.C. § 355(i) (2000); 21 C.F.R. pt. 312 (2001); see also id. § 312.22(a) (“FDA's primary objectives in reviewing an IND are … to ensure the safety and rights of subjects … .”); United States v. Garfinkel, 29 F.3d 451 (8th Cir. 1994) (reversing the dismissal of an indictment charging an investigator with violations of IND recordkeeping requirements); Findlay, Richard J., Originator Drug Development, 54 FOOD & DRUG L.J. 227, 227-28 (1999)Google ScholarPubMed; Kessler, David A., The Regulation of Investigational Drugs, 320 NEW ENG. J. MED. 281 (1989)CrossRefGoogle ScholarPubMed.

143 See 21 U.S.C. § 360j(g); 21 C.F.R. pt. 812; see also Martin v. Telectronics Pacing Sys., Inc., 105 F.3d 1090, 1095-96 (6th Cir. 1997).

144 21 C.F.R. § 56.102(c). Elsewhere, the FDA distinguishes between experimental and nonexperimental (but nonetheless investigational) medical devices governed by IDE requirements. See 61 Fed. Reg. 7011, 7011-12 (1996).

145 45 C.F.R. § 46.102(d) (2001).

146 See 61 Fed. Reg. 51,498, 51,528-29 (1996) (codified at 21 C.F.R. § 50.24 (2001)); see also Adams, James G. & Wegener, Joel, Acting Without Asking: An Ethical Analysis of the Food and Drug Administration Waiver of Informed Consent for Emergency Research, 33 ANNALS EMERGENCY MED. 218 (1999)CrossRefGoogle ScholarPubMed; Saver, Richard S., Critical Care Research and Informed Consent, 75 N.C. L. REV. 205, 249-58 (1996)Google ScholarPubMed (criticizing the FDA's approach).

147 See 55 Fed. Reg. 52,814, 52,817 (1990) (codified at 21 C.F.R. § 50.23(d)). Although some have argued that the DOD sought only to provide treatment for soldiers rather than engage in research, the FDA's waiver clearly anticipated that IND study protocols would govern the use of the unapproved drugs, that other human subject protections would remain in place, and that the DOD would collect data in pursuit of filing applications for marketing approval. See id. at 52,815-16.

148 Department of Defense Authorization Act of 1985, Pub. L. No. 98-525, § 1401(c), 98 Stat. 2492, 2615 (1984) (codified at 10 U.S.C. § 980 (2000)); see also Schuchardt, Elliott J., Distinguishing Between Research and Medical Practice During Operation Desert Storm, 49 FOOD & DRUG L.J. 271, 277-89 (1994)Google Scholar (concluding that the DOD had not conducted research in violation of this statute).

149 See Doe v. Sullivan, 756 F. Supp. 12, 16 (D.D.C.) (“The fact that the DOD will collect information on the efficacy of the drugs does not transform the strategic decision to use the unapproved drugs in combat into research.”), aff’d, 938 F.2d 1370, 1379-83 (D.C. Cir. 1991); see also Annas, George J., Changing the Consent Rules for Desert Storm, 326 NEW ENG. J. MED. 770, 772 (1992)CrossRefGoogle ScholarPubMed (agreeing that the DOD was not engaging in research); Ryan, Robyn P., Should Combat Troops Be Given the Option of Refusing Investigational Drug Treatment?, 52 FOOD & DRUG L.J. 377, 393 (1997)Google ScholarPubMed (criticizing the waiver, noting that, although “DOD did not administer the treatment with the primary intent of generating new knowledge,” the drugs were experimental in the sense that uncertainty remained about their safety and efficacy); Milner, Claire Alida, Comment, Gulf War Guinea Pigs: Is Informed Consent Optional During War?, 13 J. CONTEMP. HEALTH L. & POL’Y 199, 223-31 (1996)Google ScholarPubMed; Guy Gugliotta, Pentagon's Missteps Stalled New Vaccines, WASH. POST, Apr. 12, 2002, at A13 (reporting that the DOD never intended to pursue FDA approval).

150 See 10 U.S.C. § 1107 (2000); see also Exec. Order No. 13,139, 64 Fed. Reg. 54,175 (1999) (announcing that the President would evaluate waiver requests using the criteria set forth in the FDA's regulation). Even so, the DOD apparently has continued trying to evade this requirement. See Neely Tucker, Anthrax Vaccine Challenged: Two Suing Defense Department over Inoculation Policy, WASH. POST, May 15, 2002, at A10. But see Miller, Ruth K., Note, Informed Consent in the Military: Fighting a Losing Battle Against the Anthrax Vaccine, 28 AM. J.L. & MED. 325, 339-43 (2002)CrossRefGoogle ScholarPubMed (defending the DOD's program).

151 See 50 Fed. Reg. 42,866 (1985).

152 See 52 Fed. Reg. 19,466 (1987) (codified as amended at 21 C.F.R. § 312.34(b)(1)) (providing the following criteria for treatment IND status: (1) the drug is intended to treat a serious or immediately life-threatening disease; (2) there is no comparable or satisfactory alternative drug or other therapy available to treat that disease in the particular patient population; (3) the drug is being studied in a controlled clinical trial under an IND or clinical trials have been completed for the drug; and (4) the drug's sponsor is actively pursuing marketing approval); see also AIDS Amendments of 1988, Pub. L. No. 100-607, § 201(4), 102 Stat. 3048, 3066-67 (codified as amended at 42 U.S.C. § 300cc-12 (2000)) (endorsing the use of treatment INDs for investigational AIDS drugs).

153 See 21 C.F.R. § 312.34(c); see also 21 U.S.C. § 360bbb (2000); Annas, George J., Faith (Healing), Hope and Charity at the FDA: The Politics of AIDS Drug Trials, 34 VILL. L. REV. 771, 772 (1989)Google ScholarPubMed (criticizing these initiatives for “erod[ing] the distinction between experimentation and therapy”); id. at 795 (“The distinction between experimentation and therapy is a powerfully useful and protective one that should not be undermined.”); Salbu, Steven R., The FDA and Public Access to New Drugs: Appropriate Levels of Scrutiny in the Wake of HIV, AIDS, and the Diet Drug Debacle, 79 B.U. L. REV. 93, 113-19 (1999)Google Scholar; Marlin, Myron L., Comment, Treatment INDs: A Faster Route to Drug Approval?, 39 AM. U. L. REV. 171, 185-95 (1989)Google Scholar.

154 See 57 Fed. Reg. 13,250, 13,256 (1992) (“Under this policy, expanded availability protocols might be approved for promising investigational drugs when the evidence for effectiveness is less than that generally required for a Treatment IND… . All drugs distributed under the parallel track mechanism will be under a study protocol. Data, particularly pertaining to side effects and safety will be collected under these studies.”).

155 See Garnham, J.C., Some Observations on Informed Consent in Non-Therapeutic Research, 1 J. MED. ETHICS 138 (1975)CrossRefGoogle ScholarPubMed; Gillon, Raanan, Editorial, Medical Treatment, Medical Research and Informed Consent, 15 J. MED. ETHICS 3, 3-5 (1989)CrossRefGoogle ScholarPubMed; Mulford, Robert D., Note, Experimentation on Human Beings, 20 STAN. L. REV. 99, 101-02, 104-05 (1967)CrossRefGoogle Scholar. Until recently, the Declaration of Helsinki included such a distinction, demanding informed consent for all forms of non-therapeutic research but allowing some flexibility in cases of therapeutic research. See Annas, supra note 134, at 303 (criticizing this distinction); Churchill et al., supra note 134, at 39; Robert J. Levine, Clarifying the Concepts of Research Ethics, HASTINGS CTR. REP., June 1979, at 21, 22-23; see also World Medical Ass’n, Declaration of Helsinki, 277 JAMA 925, 926 (1997)Google Scholar; Enserink, Martin, Helsinski's New Clinical Rules: Fewer Placebos, More Disclosure, 290 SCIENCE 418 (2000)CrossRefGoogle Scholar.

156 See RENÉE C. FOX & JUDITH P. SWAZEY, SPARE PARTS: ORGAN REPLACEMENT IN AMERICAN SOCIETY 9 (1992); see also King, Nancy M.P., The Line Between Clinical Innovation and Human Experimentation, 32 SETON HALL L. REV. (forthcoming Dec. 2002)Google Scholar; Levine, Robert J., The Impact on Fetal Research of the Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 22 VILL. L. REV. 367, 380-82 (1977)Google ScholarPubMed (preferring to call it “nonvalidated practice”); Stanley Joel Reiser, Criteria for Standard Versus Experimental Therapy, HEALTH AFF., Summer 1994, at 127 (describing the oscillation between these two categories, and proposing “crossover therapy” as an intermediate category).

157 Cowan, Dale H., Innovative Therapy Versus Experimentation, 21 TORT & INS. L.J. 619, 623 (1986)Google Scholar (“Additionally, they are not undertaken in order to gain new knowledge beyond the needs of the patient. Although the use of innovative therapies may lead to the development of new knowledge, this consequence is secondary to their primary purpose of benefiting patients.”). As Dr. Cowan elaborated:

Id. at 624.

158 See id. at 621 (“It is acknowledged that all risks may not be known or totally absent. However, the degree of ignorance of the risks has been sufficiently reduced in relation to the anticipated benefits as to justify the use of the practice in a setting where the sole intent is to promote the patient's well-being.”).

159 See id. at 633 (“Innovative practices are largely unregulated.”); see also Cowan, Dale H. & Bertsch, Eva, Innovative Therapy: The Responsibility of Hospitals, 5 J. LEGAL MED. 219, 220 (1984)CrossRefGoogle ScholarPubMed (“Knowledgeable observers of medical practice have commented that each time a physician treats a patient, the physician is in effect conducting a mini-experiment since the outcome of the intervention can never precisely be predicted.”); id. at 222-24, 234, 251 (“Innovative therapies or non-validated practices occupy a gray zone of medical activities between standard medical practices and activities that are properly defined as research.”).

160 See Clarke, Michael & Chalmers, Iain, Discussion Sections in Reports of Controlled Trials Published in General Medical Journals: Islands in Search of Continents?, 280 JAMA 280, 280 (1998)CrossRefGoogle ScholarPubMed (“No other category of biomedical report has received such sustained attention, and this reflects the practical importance of controlled trials in guiding decisions in health care.”). See generally STUART J. POCOCK, CLINICAL TRIALS: A PRACTICAL APPROACH (1983).

161 See 21 C.F.R. §§ 314.126(b)(2), 860.7(f)(1)(iv) (2001); Merrill, Richard A., The Architecture of Government Regulation of Medical Products, 82 VA. L. REV. 1753, 1767, 1771, 1779-82 (1996)CrossRefGoogle Scholar; Temple, Robert, Government Viewpoint of Clinical Trials, 16 DRUG INFO. J. 10, 11-13 (1982)CrossRefGoogle Scholar; see also Oates, John A. & Wood, Alastair J.J., Editorial, The Regulation of Discovery and Drug Development, 320 NEW ENG. J. MED. 311, 312 (1989)CrossRefGoogle ScholarPubMed (“The quality of evidence obtained in [RCTs] allows physicians and patients to make rational decisions about treatment. Real freedom of choice in therapy derives from evidence that permits an informed choice.”).

162 See Necheles, Thomas, Standards of Medical Care: How Does an Innovative Medical Procedure Become Accepted?, 10 LAW MED. & HEALTH CARE 15, 17 (1982)CrossRefGoogle ScholarPubMed (“The FDA has long been accepted as the arbiter of the safety and effectiveness of drugs. No such arbiter exists in the field of innovative medical procedures.”); Spodick, David H., Numerators Without Denominators: There Is No FDA for the Surgeon, 232 JAMA 35, 35-36 (1975)CrossRefGoogle ScholarPubMed; see also Banta, H. David & Thacker, Stephen B., The Case for Reassessment of Health Care Technology: Once Is Not Enough, 264 JAMA 235, 236-37, 239 (1990)CrossRefGoogle ScholarPubMed (explaining that most RCTs focus on new drugs, resulting in less information about older technologies and surgical techniques).

163 See Note, The Open-Ended Investigation: A Method for Regulation of New Medical Services, 91 YALE L.J. 550, 566-67 (1982)CrossRefGoogle Scholar; cf. Bunker, J.P. et al., Surgical Innovation and Its Evaluation, 200 SCIENCE 937, 941 (1978)CrossRefGoogle ScholarPubMed (calling on the biomedical research community to generate the missing information); Wennberg, John E., The Paradox of Appropriate Care, 258 JAMA 2568, 2569 (1987)CrossRefGoogle ScholarPubMed (same). Occasionally, and controversially, the FDA will assert jurisdiction over certain medical procedures by demanding the submission of INDs. See Rick Weiss, FDA to Regulate Certain Fertilization Procedures, WASH. POST, July 11, 2001, at A2; Rick Weiss, Legal Barriers to Human Cloning May Not Hold Up, WASH. POST, May 23, 2001, at A1.

164 See Philip J. Hilts, Study or Human Experiment? Face-Lift Project Stirs Ethical Concerns, N.Y. TIMES, June 21, 1998, at A25 (reporting that plastic surgeons performed different face lift procedures on opposite halves of their patients’ faces and then tracked them to see whether one technique provided better results over time, publishing their initial results in a professional journal but avoiding IRB requirements because the study did not involve an FDA-regulated product and received no federal funding); Rick Weiss, Fertility Innovation or Exploitation? Regulatory Void Allows for Trial—and Error—Without Patient Disclosure Rules, WASH. POST, Feb. 9, 1998, at A1; see also R. Alta Charo, Human Subjects Have It Worse Than Guinea Pigs, CHRON. HIGHER EDUC., June 25, 1999, at A64 (“[A]n unknown number of people have been used as subjects in privately financed research without their knowledge, and without the essential protections built into the federal regulations.”).

165 See Chalmers, Iain & Silverman, William A., Professional and Public Double Standards on Clinical Experimentation, 8 CONTROLLED CLINICAL TRIALS 388, 389 (1987)CrossRefGoogle ScholarPubMed (noting that “a mischievous view has been promoted that the interests of the vast number of patients involved in the poorly controlled experiments of informal medical ‘tinkering’ are less in need of protection”); Lantos, John, Informed Consent: The Whole Truth for Patients?, 72 CANCER 2811, 2814-15 (1993)3.0.CO;2-G>CrossRefGoogle ScholarPubMed; Truog et al., supra note 122, at 804 (“argu[ing] that the current approach to informed consent is at least partially off target, in that patients are often ‘protected’ from clinical trials under circumstances in which the risks associated with participation in the trial are virtually nil, but they receive no protection from physicians who want to experiment with new treatments in the name of therapeutic innovation”); id. at 806 (“Greater respect for the autonomy of patients means that many experiments that are currently undertaken in the context of clinical care under the guise of therapeutic innovation should be subject to much greater scrutiny.”).

166 See Miller, Frances H., Health Care Information Technology and Informed Consent: Computers and the Doctor-Patient Relationship, 31 IND. L. REV. 1019, 1039 (1998)Google ScholarPubMed (“[C]linical innovations not involving the experimental use of drugs or devices still remain in a basically unregulated limbo.”); Strauss, Michael J., The Political History of the Artificial Heart, 310 NEW ENG. J. MED. 332, 335-36 (1984)CrossRefGoogle ScholarPubMed; Tonelli, Mark R. et al., Clinical Experimentation: Lessons from Lung Volume Reduction Surgery, 110 CHEST 230, 232-37 (1996)CrossRefGoogle ScholarPubMed.

167 See Edenfield v. Vahid, 621 So. 2d 1192, 1196 (La. Ct. App. 1993) (noting the view of one member of a medical malpractice review panel “that the way [surgical] trends change is through some ‘mavericks’ trying different techniques”); Capron, supra note 7, at 357-60, 432; Cowan, supra note 157, at 622 (“[P]hysicians planning to undertake innovative therapies may have personal goals in addition to the interests of the patients. Such goals may include a desire for career advancement or a desire to gain recognition from pioneering a new procedure.”); see also George J. Annas, Baby Fae: The “Anything Goes” School of Human Experimentation, HASTINGS CTR. REP., Feb. 1985, at 15, 16 (criticizing baboon heart transplant); Dolan, Andrew K., The Law and the Maverick Health Practitioner, 26 ST. LOUIS U. L.J. 627, 627, 674 (1982)Google Scholar (criticizing licensing boards and other mechanisms used to promote conformity).

168 See Kaldjian, Lauris C. et al., Insertion of Femoral-Vein Catheters for Practice by Medical House Officers During Cardiopulmonary Resuscitation, 341 NEW ENG. J. MED. 2088, 2089-90 (1999)CrossRefGoogle ScholarPubMed; Denise Grady, Doctors’ Practice on the Dying Should Be Stopped, Study Says, N.Y. TIMES, Dec. 30, 1999, at A18 (noting that some hospitals encouraged interns and residents to practice, without having secured consent, unnecessary invasive procedures on patients for whom resuscitation efforts had failed). Because the practice is not intended to produce generalizable knowledge, it does not qualify as “research” under the federal regulations.

169 See Engel, Jerome, Editorial, Finally, A Randomized, Controlled Trial of Epilepsy Surgery, 345 NEW ENG. J. MED. 365, 365 (2001)CrossRefGoogle ScholarPubMed (“[A]n important obstacle to surgery's taking what many believe to be its rightful place in the therapeutic armamentarium for epilepsy has been our failure to apply the gold standard for the evaluation of therapeutic efficacy—the [RCT].”); Moseley, J. Bruce et al., A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee, 347 NEW ENG. J. MED. 81 (2002)CrossRefGoogle ScholarPubMed.

170 See Opinion 2.07, in AMA COUNCIL ON ETHICAL & JUDICIAL AFF., CODE OF MEDICAL ETHICS: CURRENT OPINIONS WITH ANNOTATIONS 21 (2000) (“In clinical investigation primarily for treatment … [v]oluntary written consent must be obtained … following: (a) disclosure that the physician intends to use an investigational drug or experimental procedure … .”); see also 46 Fed. Reg. 8942, 8943 (1981) (“‘In order to protect self-determination and promote rational decisionmaking, more, not less, information should probably be required to be disclosed in the experimental therapy situation than in the purely experimental setting with a normal volunteer.’” (citation omitted)).

171 See Cowan, supra note 157, at 626; see also BARRY R. FURROW ET AL., HEALTH LAW: CASES, MATERIALS AND PROBLEMS 230 (4th ed. 2001) (“It is generally not difficult to determine whether a new drug or device is being used experimentally. It is often very difficult to determine whether a particular surgical procedure is experimental.”). The IRS may labor under a similar misconception when reviewing claims by drug companies seeking tax deductions and tax credits for conducting “research” and “experimentation.” See Crimm, Nina J., A Tax Proposal to Promote Pharmacologic Research, to Encourage Conventional Prescription Drug Innovation and Improvement, and to Reduce Product Liability Claims, 29 WAKE FOREST L. REV. 1007, 1049-55, 1069-70 (1994)Google Scholar.

172 See Gelijns, Annetine C. et al., i>Capturing the Unexpected Benefits of Medical Research, 339 NEW ENG. J. MED. 693, 693 (1998)CrossRefGoogle ScholarPubMed (“The end of the research-and-development process does not entail the elimination of all, or even most, of the uncertainties surrounding medical innovation.”); Ray, Wayne A. et al., Evaluating Drugs After Their Approval for Clinical Use, 329 NEW ENG. J. MED. 2029, 2029-30 (1993)CrossRefGoogle ScholarPubMed; Woosley, Raymond, Opportunities in Phase IV to Improve Drug Development, 52 FOOD & DRUG L.J. 185, 185-86 (1997)Google ScholarPubMed; see also Annas, supra note 153, at 773 n.6 (“Rather than characterize any particular drug as a ‘research drug’ versus a ‘therapy drug,’ it is probably more accurate to think of a drug as falling on a continuum from ‘experimental’ to ‘investigational’ to ‘suspected effective’ to ‘nonvalidated’ to ‘proven effective.’”).

173 See GENERAL ACCOUNTING OFFICE, FDA DRUG REVIEW: POST APPROVAL RISKS, PEMD- 90-15, at 3 (1990) (concluding that more than half of all drugs approved between 1976 and 1985 had serious risks that were discovered only after approval); Lasser, Karen E. et al., Timing of New Black Box Warnings and Withdrawals for Prescription Medications, 287 JAMA 2215, 2218-19 (2002)CrossRefGoogle ScholarPubMed; Naomi Aoki, A Question of Speed and Safety, BOSTON GLOBE, Nov. 28, 2001, at G1 (noting “the growing number of drugs that have been recalled in the past three years—nearly a dozen implicated in more than 1,000 deaths”); Abigail Zuger, Caution: That Dose May Be Too High, N.Y. TIMES, Sept. 17, 2002, at F1; see also GENERAL ACCOUNTING OFFICE, MEDICAL DEVICES: EARLY WARNING OF PROBLEMS IS HAMPERED BY SEVERE UNDERREPORTING, PEMD-87-1, at 3 (1986) (finding that less than one percent of adverse events associated with the use of medical devices in hospitals were reported to the FDA).

174 See 21 U.S.C. § 355(k)(1) (2000); 21 C.F.R. §§ 310.305, 314.80 (2001). Similar requirements apply to medical devices. See 21 U.S.C. § 360l; 21 C.F.R. § 814.82.

175 Noah, Barbara A., Adverse Drug Reactions: Harnessing Experiential Data to Promote Patient Welfare, 49 CATH. U. L. REV. 449, 461 (2000)Google Scholar; see also id. at 458-83 (elaborating on these requirements); 50 Fed. Reg. 7452, 7471 (1985) (“The much larger patient population and longer period of use associated with the marketing of a drug provides, for the first time, the opportunity to collect information on rare, latent, and long-term effects, some of which may be serious.”); Gilhooley, Margaret, Innovative Drugs, Products Liability, Regulatory Compliance, and Patient Choice, 24 SETON HALL L. REV. 1481, 1492 (1994)Google Scholar; Gilhooley, supra note 110, at 936 (recognizing that “the initial use of a drug is, in effect, a continuation of the testing” phase); Merrill, Richard A., Compensation for Prescription Drug Injuries, 59 VA. L. REV. 1, 20, 87 (1973)CrossRefGoogle Scholar (“Most [adverse drug] reactions are the by-product of what amounts to government approved medical experimentation … .”); Teff, Harvey, Drug Approval in England and the United States, 33 AM. J. COMP. L. 567, 579 (1985)CrossRefGoogle Scholar (The United Kingdom “has more readily accommodated to the unpalatable truth that … serious, rare side effects will not necessarily manifest themselves until a drug has been used by a far greater proportion of the population than is feasible even with extensive premarket testing.”).

176 See Rochelle Sharpe, MedWatch System Comes Under Fire: FDA Defends Drug Monitoring as Physicians, Advocates Are Cautious, WALL ST. J., June 24, 1998, at B5; see also Temple, Robert J. & Himmel, Martin H., Editorial, Safety of Newly Approved Drugs: Implications for Prescribing, 287 JAMA 2273, 2275 (2002)CrossRefGoogle ScholarPubMed.

177 See 65 Fed. Reg. 81,082, 81,088 (2000) (proposing to require the placement of an inverted solid black triangle on the labels of drugs approved for fewer than three years and that contain a new molecular entity, a new active ingredient combination, are indicated for a new population, or utilize a different delivery system); Gilhooley, supra note 110, at 935. The spontaneous reporting rules require the quarterly submission of all adverse drug experience reports during the first three years of marketing and then annually thereafter. See 21 C.F.R. § 314.80(c)(2)(i); see also Noah, supra note 175, at 471 (“The initial close scrutiny during the first three years … reflects the reality that the drug's safety profile will continue to develop as more patients take the product. Some industry insiders refer to this early marketing period as ‘the red zone.’”); id. at 479 (adding that “spontaneous reporting of ADRs peaks at the end of the second year of a drug's marketing”).

178 See Mahinka, Stephen Paul & Bierman, M. Elizabeth, Direct-to-OTC Marketing of Drugs: Possible Approaches, 50 FOOD & DRUG L.J. 49 (1995)Google ScholarPubMed; Marc Kaufman, Nonprescription Prilosec Backed, WASH. POST, June 22, 2002, at A8 (“Company scientists argued … that a decade of use by up to 10 million people a day had determined that Prilosec was safe and effective.”).

179 See American Med. Ass’n, Reporting Adverse Drug and Medical Device Events: Report of the AMA's Council on Ethical and Judicial Affairs, 49 FOOD & DRUG L.J. 359, 362-65 (1994)Google Scholar.

180 See 21 U.S.C. § 360i; 21 C.F.R. pt. 803; Basile, Edward M., The Safe Medical Devices Act of 1990: Postmarket Surveillance, MDR, and Other Postmarket Issues, 46 FOOD DRUG COSM. L.J. 165, 166-69 (1991)Google Scholar; see also 67 Fed. Reg. 38,878, 38,887 (2002) (to be codified at 21 C.F.R. pt. 822) (adopting special postmarket surveillance requirements applicable to certain high-risk medical devices). A similar requirement applies to childhood vaccines. See 42 U.S.C. § 300aa-25(b) (2000).

181 See 21 U.S.C. § 356b (2000); 21 C.F.R. § 310.303; see also Fleshner, Robert L., Post-Marketing Surveillance of Prescription Drugs: Do We Need to Amend the FDCA?, 18 HARV. J. ON LEGIS. 327, 328-29, 338 (1981)Google Scholar; Mattison, Nancy & Richard, Barbara W., Postapproval Research Requested by the FDA at the Time of NCE Approval: 1970-1984, 21 DRUG INFO. J. 309, 323 (1987)CrossRefGoogle Scholar (finding that the agency had imposed such a condition on almost half of all new drug approvals); Rossi, Allen C. et al., Discovery of Adverse Drug Reactions: A Comparison of Selected Phase IV Studies with Spontaneous Reporting Methods, 249 JAMA 2226 (1983)CrossRefGoogle ScholarPubMed.

182 See 21 C.F.R. §§ 314.510, 601.41 (2001); see also Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, § 112(b)(2)(A), 111 Stat. 2296, 2309-10 (codified at 21 U.S.C. § 356(b)(2)(A) (2000)) (codifying these “fast track” procedures); Parver, Deborah G., Comment, Expediting the Drug Approval Process: An Analysis of the FDA Modernization Act of 1997, 51 ADMIN. L. REV. 1249, 1262 (1999)Google Scholar; Marc Kaufman, FDA Acts to Speed Bioterror Medicines, WASH. POST, May 31, 2002, at A1 (describing new rule allowing approval of biowarfare treatments based largely on animal studies).

183 See 57 Fed. Reg. 58,942, 58,957 (1992) (“Drugs approved under these provisions are not considered experimental drugs for their approved uses.”); see also Dale E. Hammerschmidt, Understanding the FDA's IND Process, in INSTITUTIONAL REVIEW BOARD: MANAGEMENT AND FUNCTION 323, 324 (Robert Amdur & Elizabeth Bankert eds., 2002) (“A simple example of an allowable study [not subject to IND requirements] would be a postmarketing evaluation of a licensed drug to test whether its efficacy in ordinary clinical use is similar to that which had been found in carefully selected subject groups in Phase III trials.”). The FDA's human subject protection regulations clearly recognize that some drug research of interest to the agency may occur without IRB supervision. See 21 C.F.R. § 56.103(b) (“The determination that a clinical investigation may not be considered in support of an application for a research or marketing permit does not, however, relieve the applicant for such a permit of any obligation under any other applicable regulations to submit the result of the investigation to the [FDA].”). If conducted at an institution that receives federal research funding, HHS rules for the protection of human subjects normally would apply to such clinical trials.

184 See Chris Adams, FDA Weighs Requests to Return Lotronex to Consumer Market, WALL ST. J., Apr. 19, 2001, at B10; Denise Grady, FDA Pulls a Drug, and Patients Despair, N.Y. TIMES, Jan. 30, 2001, at F1. The manufacturers withdrew the drug from the market less than ten months after approval. Of the 300,000 patients who had taken it during that brief period, seventy developed severe constipation or ischemic colitis (a lack of blood flow to the colon); some cases required surgical intervention, and five people died. The majority of patients on the drug who suffered no serious side effects protested the withdrawal because it helped them to cope with a condition that significantly interfered with their daily life activities. In negotiations over returning the drug to the market, the manufacturer rejected FDA proposals to limit prescribing to gastroenterologists who had been “certified” to prescribe the drug, and to prevent off-label prescribing. An advisory committee recently encouraged the agency to resurrect Lotronex with restrictions on access. See Marc Kaufman, Panel Suggests Irritable-Bowel Drug Be Sold Again, WASH. POST, Apr. 24, 2002, at A7.

185 See Am. Pharm. Ass’n v. Weinberger, 377 F. Supp. 824, 830 (D.D.C. 1974) (“When an IND exemption is approved, the Commissioner may, of course, severely restrict the distribution of the exempted drug to bona fide researchers and clinicians.”), aff’d, 530 F.2d 1054 (D.C. Cir. 1976); Note, The Open-Ended Investigation, supra note 163, at 560-62, 565.

186 See Marc Kaufman, FDA Reapproves Bowel Drug After Pulling It for Safety, WASH. POST, June 8, 2002, at A4.

187 See Buckman Co. v. Plaintiffs’ Legal Comm., 531 U.S. 341, 350-51 & n.5 (2001).

188 See H.R. REP. NO. 102-1064, at 22-23 (1992) (noting that physicians “are accustomed to prescribing drugs for off-label uses”).

189 See Fran Kritz, FDA Seeks to Add Drugs’ New Uses to Labels, WASH. POST, Mar. 29, 1994, at Z11 (citing an AMA official's estimate of 40-60%); see also Milt Freudenheim, FDA Gets Tough on Drugs Offered for Unapproved Uses, N.Y. TIMES, June 29, 1991, § 1, at 1 (placing the figure at 25% of the 1.6 billion prescriptions written annually).

190 See Laetz, Thomas & Silberman, George, Reimbursement Policies Constrain the Practice of Oncology, 266 JAMA 2996 (1991)CrossRefGoogle ScholarPubMed; Moertel, Charles G., Off-Label Drug Use for Cancer Therapy and National Health Care Priorities, 266 JAMA 3031 (1991)CrossRefGoogle ScholarPubMed.

191 See Archer, John D., Editorial, The FDA Does Not Approve Uses of Drugs, 252 JAMA 1054, 1055 (1984)CrossRefGoogle Scholar; Mundy, Gregory R. et al., Current Medical Practice and the Food and Drug Administration: Some Evidence for the Existing Gap, 229 JAMA 1744, 1747 (1974)CrossRefGoogle ScholarPubMed (describing widespread off-label use of propranolol for angina and hypertension); see also Barrett-Connor, Elizabeth et al., Raloxifene and Cardiovascular Events in Osteoporotic Postmenopausal Women, 287 JAMA 847 (2002)CrossRefGoogle ScholarPubMed (reporting that a drug approved for use against osteoporosis may reduce the risk of heart attack).

192 See Turner, Sean et al., Unlicensed and Off Label Drug Use in Paediatric Wards: Prospective Study, 316 BRIT. MED. J. 343, 344 (1998)CrossRefGoogle ScholarPubMed; Wilson, John T., An Update on the Therapeutic Orphan, 104 PEDIATRICS 585, 585-86 (1999)Google ScholarPubMed (part of a symposium issue on the subject); Karst, Kurt R., Comment, Pediatric Testing of Prescription Drugs: The Food and Drug Administration's Carrot and Stick for the Pharmaceutical Industry, 49 AM. U. L. REV. 739, 741 n.5 (2000)Google ScholarPubMed (noting estimates that roughly 80% of drugs on the market in 1997 had not undergone testing for pediatric uses); Robert Pear, President to Order Drug Makers to Conduct Pediatric Studies, N.Y. TIMES, Aug. 13, 1997, at A17 (reporting that less than half of the drugs regularly used in children have been studied in pediatric populations); see also Rachel Zimmerman, Child Play: Pharmaceutical Firms Win Big on Plan to Test Adult Drugs on Kids, WALL ST. J., Feb. 5, 2001, at A1.

193 48 Fed. Reg. 26,720, 26,733 (1983); see also 21 C.F.R. § 312.2(d) (2001) (explaining that the FDA's investigational new drug requirements “do[] not apply to the use in the practice of medicine for an unlabeled indication of [an approved] new drug”); United States v. Evers, 453 F. Supp. 1141, 1148-49 (M.D. Ala. 1978), aff’d, 643 F.2d 1043, 1048 (5th Cir. 1981); FTC v. Simeon Mgmt. Corp., 391 F. Supp. 697, 706-07 (N.D. Cal. 1975), aff’d, 532 F.2d 708, 717 (9th Cir. 1976) (“FDA has specifically recognized the legality of using drugs for purposes other than those for which they have been found safe and effective.”). Physicians cannot, however, commercialize off-label uses of approved products or administer products not yet approved for any use without complying with FDA requirements governing investigational new drugs and devices. See United States v. Burzynski Cancer Research Inst., 819 F.2d 1301, 1304-05 (5th Cir. 1987); Cowan v. United States, 5 F. Supp. 2d 1235, 1240 (N.D. Okla. 1998); Retkwa v. Orentreich, 579 N.Y.S.2d 577 (Sup. Ct. 1991).

194 See Use of Approved Drugs for Unlabeled Indications, FDA DRUG BULLETIN, Apr. 1982, at 5 (“Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations, subsequently confirmed by well-planned and executed clinical investigations.”); see also Weaver v. Reagan, 886 F.2d 194, 198 (8th Cir. 1989) (“Thus, the fact that FDA has not approved labeling of a drug for a particular use does not necessarily bear on those uses of the drug that are established within the medical and scientific community as medically appropriate.”); 59 Fed. Reg. 59,820, 59,821 (1994); Gina Kolata, Drugs that Deliver More Than Originally Promised, N.Y. TIMES, Apr. 5, 1998, § 4, at 3.

195 See 21 U.S.C. § 396 (2000) (medical device regulation); 42 U.S.C. § 1395 (2000) (“Nothing in [Medicare] shall be construed to authorize any Federal officer or employee to exercise any supervision or control over the practice of medicine or the manner in which medical services are provided.”); 37 Fed. Reg. 16,503, 16,504 (1972) (“[I]t is clear that Congress did not intend the [FDA] to regulate or interfere with the practice of medicine … .”).

196 See 42 U.S.C. § 1396r-8(k)(6) (2000); see also id. § 1395x(t)(2)(B) (authorizing Medicare reimbursement for off-label uses of oncology drugs if consistent with medical compendia or the peerreviewed literature); Noah, Lars, Sanctifying Scientific Peer Review: Publication as a Proxy for Regulatory Decisionmaking, 59 U. PITT. L. REV. 677, 683 (1998)Google Scholar; Raiford, Drusilla S. et al., Determining Appropriate Reimbursement for Prescription Drugs: Off Label Uses and Investigational Therapies, 49 FOOD & DRUG L.J. 37, 38 (1994)Google Scholar (“Historically, coverage for experimental drugs has been, with some exceptions, an express contractual exclusion … . Off-label uses of approved drugs, on the other hand, generally have been covered by third-party payors.”); id. at 41, 60 (explaining that private insurers have struggled in maintaining this distinction in the face of changing FDA policies).

197 Promotion of Drugs and Medical Devices for Unapproved Uses: Hearing Before the Human Resources and Intergovernmental Relations Subcomm. of the House Comm. on Government Operations, 102d Cong., at 103 (1991) (statement of George D. Lundberg, editor of the Journal of the American Medical Association) (“There are too many variations in clinical circumstances and too much time delay in regulations to allow the government to impede the physician's ability to practice in these regards when it is medically appropriate.”).

198 See Bell v. Maricopa Med. Ctr., 755 P.2d 1180, 1182 (Ariz. 1988) (alleging malpractice for the failure to use an approved drug for an off-label use); Bridges v. Shelby Women's Clinic, 323 S.E.2d 372, 374-76 (N.C. Ct. App. 1984) (same); American Academy of Pediatrics, Committee on Drugs, Unapproved Uses of Approved Drugs: The Physician, the Package Insert, and the FDA, 62 PEDIATRICS 262, 263 (1978)Google Scholar. In one case, a physician defending against a malpractice claim for exceeding the manufacturer's recommended dose sought to introduce an editorial from a medical journal explaining that best medical practice often requires disregarding prescription drug labeling. See O’Brien v. Angley, 407 N.E.2d 490, 492-94 (Ohio 1980) (holding that the trial judge erred in admitting this editorial into evidence).

199 See, e.g., 62 Fed. Reg. 64,074, 64,081 (1997); Randall, Teri, FDA Scrutinizes “Off-Label” Promotions, 266 JAMA 11 (1991)CrossRefGoogle ScholarPubMed (describing problems with off-label uses of approved products such as Retin A); Shapiro, Sidney A., Limiting Physician Freedom to Prescribe a Drug for Any Purpose: The Need for FDA Regulation, 73 NW. U. L. REV. 801, 819-22 (1978)Google Scholar (describing problems encountered with the off-label uses of methotrexate, chloromycetin, and DES).

200 See Femrite v. Abbott Nw. Hosp., 568 N.W.2d 535, 541 (Minn. Ct. App. 1997) (explaining, in the course of affirming partial summary judgment granted to a malpractice defendant, that “a hospital could acquire the same device from a manufacturer either through routine commercial means for ‘off-label’ use or as an investigational device under an IDE”); Staudt v. Froedtert Mem’l Lutheran Hosp., 580 N.W.2d 361, 363-64 (Wis. Ct. App. 1998); see also 21 C.F.R. § 312.3(b) (“Clinical investigation means any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.”). An investigator may not, however, engage in an off-label use of an approved product as part of a clinical trial concerning some other procedure but in violation of the study protocol approved by the IRB and without securing the subject's informed consent. See Tivoli v. United States, 1996 WL 1056005, at *5-14 (S.D.N.Y. 1996) (awarding damages for malpractice by government physicians conducting a clinical trial under the supervision of an NIH IRB); see also Blanton v. United States, 428 F. Supp. 360, 361-63 (D.D.C. 1977) (imposing liability on a government hospital for administering an FDA-approved drug to a patient as part of a clinical trial to determine its effectiveness beyond the labeled shelf life after the patient had specifically declined to participate as a subject).

201 Smithells, Richard, Iatrogenic Hazards and Their Effects, 51 (Supp. 2) POSTGRAD. MED. J. 39, 41 (1975)Google ScholarPubMed; see also 60 Fed. Reg. 49,086, 49,090 (1995) (noting that an IRB rejected a proposed study of high dose epinephrine for cardiac arrest because some of the clinicians at that institution already used it as standard therapy).

202 This has led some commentators to suggest exempting more types of clinical trials from federal requirements. See Truog et al., supra note 122, at 805-06. The government already authorizes IRBs to exempt certain types of “minimal risk” studies from the informed consent requirements. See 45 C.F.R. § 46.116(d) (2001); see also id. § 46.110 (allowing expedited IRB review); Paulette W. Campbell, U.S. Agencies Seek to Expand Expedited Reviews of Research: Officials See Little Risk to Humans in Certain Studies, CHRON. HIGHER EDUC., Apr. 3, 1998, at A33 (describing proposals to expand the exempt categories).

203 See Saver, supra note 146, at 225 (“[N]ovel therapies administered with the primary intent of benefitting the immediate patient will not yield much more than anecdotal evidence.”).

204 See Jadad, Alejandro R. & Rennie, Drummond, Editorial, The Randomized Controlled Trial Gets a Middle-Aged Checkup, 279 JAMA 319 (1998)CrossRefGoogle ScholarPubMed; Editorial, Fifty Years of Randomised Controlled Trials, 317 BRIT. MED. J. 1165 (1998)Google Scholar.

205 Greer, Ann Lennarson, The State of the Art Versus the State of the Science: The Diffusion of New Medical Technologies into Practice, 4 INT’L J. TECH. ASSESSMENT IN HEALTH CARE 5, 9 (1988)CrossRefGoogle Scholar; see also Belkin, Gary S., The New Science of Medicine, 19 J. HEALTH POL. POL’Y & L. 801, 802, 808 (1994)CrossRefGoogle ScholarPubMed (conceding that “potentially dangerous and risky procedures were advocated on little more than anecdote and fashion,” but ultimately “emphasizing an important role for the generation of knowledge in specific patient encounters”); Hunter, Kathryn Montgomery, “There Was This One Guy …”: The Uses of Anecdotes in Medicine, 29 PERSP. IN BIO. & MED. 619, 629-30 (1986)CrossRefGoogle Scholar; Schwartz, Rebecca K. et al., Physician Motivations for Nonscientific Drug Prescribing, 28 SOC. SCI. & MED. 577, 579, 581 (1989)CrossRefGoogle ScholarPubMed (“[H]ow can we understand the fact that over a quarter of the reasons given for nonscientific prescribing stemmed from a deep skepticism about clinical trials, from a belief that clinical experience, rather than scientific evidence, should govern clinical practice?”); Tanenbaum, Sandra J., Knowing and Acting in Medical Practice: The Epistemological Politics of Outcomes Research, 19 J. HEALTH POL. POL’Y & L. 27, 34-40 (1994)CrossRefGoogle ScholarPubMed; Wax, Amy L., Technology Assessment and the Doctor- Patient Relationship, 82 VA. L. REV. 1641, 1648 (1996)CrossRefGoogle ScholarPubMed (“[I]n actual medical practice, [choices] are often based not on accurate information but on intuition, prejudice, anecdote, or unsubstantiated lore.”).

206 See Burnum, John F., Medical Practice A La Mode: How Medical Fashions Determine Medical Care, 317 NEW ENG. J. MED. 1220 (1987)CrossRefGoogle Scholar; Grimes, David A., Technology Follies: The Uncritical Acceptance of Medical Innovation, 269 JAMA 3030, 3031-32 (1993)CrossRefGoogle ScholarPubMed; McKinlay, John B., From “Promising Report” to “Standard Procedure”: Seven Stages in the Career of a Medical Innovation, 59 MILBANK Q. 374, 380-85, 400 (1981)CrossRefGoogle Scholar; Moses, Lincoln E. & Brown, Byron Wm. Jr., Experiences with Evaluating the Safety and Efficacy of Medical Technologies, 5 ANN. REV. PUB. HEALTH 267, 288 (1984)CrossRefGoogle ScholarPubMed (“Surgery provides many examples of procedures that have found broad acceptance before reliable evaluation and then been rejected later for inefficacy or other problems.”).

207 See Mehlman, Maxwell J., Health Care Cost Containment and Medical Technology: A Critique of Waste Theory, 36 CASE W. RES. L. REV. 778, 786 (1986)Google Scholar (“Medical history reveals a number of technologies that flourished for a time but that were eventually determined to be ineffective.”); Perry, Seymour, The Brief Life of the National Center for Health Care Technology, 307 NEW ENG. J. MED. 1095, 1097-98 (1982)CrossRefGoogle ScholarPubMed; Temple, Robert, Commentary on “The Architecture of Government Regulation of Medical Products”, 82 VA. L. REV. 1877, 898-90 (1996)CrossRefGoogle Scholar (describing published RCTs finding that off-label uses of drugs in cardiac patients not only failed to work but actually increased mortality); id. at 1902 (“Without evidence we are back in the past, where bleeding, purging and heaven knows what else, all supported by expert opinion and elaborate rationales, were the standard treatments … .”); Susan Okie, Trial of Antibiotics for Chronic Lyme Disease Halted, WASH. POST, June 13, 2001, at A2 (reporting that a study forthcoming in the New England Journal of Medicine “casts doubt on some doctors’ practice of treating people with chronic Lyme disease with antibiotics for months or years on the theory that microbes hiding in the body are responsible for the symptoms”).

208 See Noah, Lars, Medicine's Epistemology: Mapping the Haphazard Diffusion of Knowledge in the Biomedical Community, 44 ARIZ. L. REV. 373 (2002)Google Scholar.

209 See Nelson, Eugene C. et al., Building Measurement and Data Collection into Medical Practice, 128 ANNALS INTERNAL MED. 460, 465 (1998)CrossRefGoogle ScholarPubMed.

210 See Chalmers, Thomas C., The Clinical Trial, 59 MILBANK Q. 324, 325 (1981)CrossRefGoogle ScholarPubMed. In fact, some commentators have distinguished research from treatment by noting the prohibition on deviating from a study protocol in precisely these sorts of ways. See ROBERT J. LEVINE, ETHICS AND REGULATION OF CLINICAL RESEARCH 10 (2d ed. 1986) (“[T]he individualized dosage adjustments and changes in therapeutic modalities are less likely to occur in the context of a clinical trial than they are in the practice of medicine … [and this represents] one of the burdens imposed on the patient-subject i[n] a clinical trial.”).

211 See Guyatt, Gordon et al., Determining Optimal Therapy: Randomized Trials in Individual Patients, 314 NEW ENG. J. MED. 889 (1986)CrossRefGoogle ScholarPubMed; Guyatt, Gordon H. et al., The N-of-1 Randomized Controlled Trial: Clinical Usefulness, 112 ANNALS INTERNAL MED. 293, 297-98 (1990)CrossRefGoogle ScholarPubMed; Larson, Eric B. et al., Randomized Clinical Trials in Single Patients During a 2-Year Period, 270 JAMA 2708, 2712 (1993)CrossRefGoogle ScholarPubMed. This differs from the occasional example of a researcher serving as his own healthy volunteer. See Neuhauser, Duncan, More Tales from Institutional Review Boards, 4 HEALTH MATRIX 153, 153 (1994)Google ScholarPubMed (describing one researcher who ingested H. pylori to test his theory that peptic ulcers had a bacterial origin); see also DAVID J. ROTHMAN, STRANGERS AT THE BEDSIDE: A HISTORY OF HOW LAW AND BIOETHICS TRANSFORMED MEDICAL DECISION MAKING 26 (1991) (describing a tradition among physicians of first trying a new treatment on themselves).

212 See Dans, Antonio L. et al., Users’ Guides to the Medical Literature: XIV. How to Decide on the Applicability of Clinical Trial Results to Your Patient, 279 JAMA 545 (1998)CrossRefGoogle ScholarPubMed; Kassirer, Jerome P., Clinical Problem-Solving, 326 NEW ENG. J. MED. 60, 60 (1992)CrossRefGoogle ScholarPubMed (“Controlled studies guide us in the right direction, but only occasionally do patients match the study population precisely. The art of medicine involves interpolating between data points … .”); see also Noah, Barbara A., Racial Disparities in the Delivery of Health Care, 35 SAN DIEGO L. REV. 135, 153 & n.68 (1998)Google ScholarPubMed (noting significant racial and ethnic variations in drug metabolism that clinical trials often fail to take into account); Noah, Lars, The Coming Pharmacogenomics Revolution: Tailoring Drugs to Fit Patients’ Genetic Profiles, 43 JURIMETRICS J. (forthcoming Mar. 2003)Google Scholar.

213 See Mahon, Jeffrey et al., Randomised Study of N of 1 Trials Versus Standard Practice, 312 BRIT. MED. J. 1069, 1072 (1996)CrossRefGoogle Scholar (“[D]espite endorsements of the technique, n of 1 trials are rarely used. This is probably because of the extra effort they demand … .”). When a patient experiences an adverse reaction to treatment, a physician may use a “dechallenge/rechallenge” procedure to determine whether the treatment really caused the side effect, see Glastetter v. Novartis Pharm. Corp., 252 F.3d 986, 990-91 (8th Cir. 2001), but this approach differs from an N-of-1 RCT designed to gauge efficacy.

214 See Moses, Lincoln E., The Series of Consecutive Cases as a Device for Assessing Outcomes of Intervention, 311 NEW ENG. J. MED. 705, 709-10 (1984)CrossRefGoogle Scholar; id. at 705 (“An air of serving the common good clings to the process of reporting as general information the results of one's own extensive experience. Medicine enjoys a long tradition of such literature … .”).

215 See Brewer, Timothy & Colditz, Graham A., Postmarketing Surveillance and Adverse Drug Reactions: Current Perspectives and Future Needs, 281 JAMA 824, 825-28 (1999)CrossRefGoogle ScholarPubMed; Friedman, Michael A. et al., The Safety of Newly Approved Medicines: Do Recent Market Withdrawals Mean There Is a Problem?, 281 JAMA 1728, 1728-29 (1999)CrossRefGoogle Scholar (describing a report from Mayo Clinic researchers of twenty-four cases of valvular disease and aortic and mitral valve regurgitation in patients taking fenfluramine in combination with phentermine); see also supra notes 173-77 and accompanying text (discussing the FDA's adverse drug experience reporting mechanisms).

216 See Nelson v. American Home Prods. Corp., 92 F. Supp. 2d 954, 969-70 (W.D. Mo. 2000).

217 See Anderson, Christopher, Measuring What Works in Health Care, 263 SCIENCE 1080 (1994)CrossRefGoogle ScholarPubMed; Epstein, Arnold M., The Outcomes Movement—Will It Get Us Where We Want to Go?, 323 NEW ENG. J. MED. 266, 267 (1990)CrossRefGoogle ScholarPubMed; Horwitz, Ralph I. et al., Developing Improved Observational Methods for Evaluating Therapeutic Effectiveness, 89 AM. J. MED. 630, 636-37 (1990)CrossRefGoogle ScholarPubMed; Relman, Arnold S., Assessment and Accountability: The Third Revolution in Medical Care, 319 NEW ENG. J. MED. 1220 (1988)CrossRefGoogle ScholarPubMed.

218 See Polanczyk, Carisi A. et al., Right Heart Catheterization and Cardiac Complications in Patients Undergoing Noncardiac Surgery: An Observational Study, 286 JAMA 309 (2001)CrossRefGoogle ScholarPubMed; see also Ceci Connolly, Mammography Review Shatters the Status Quo; Doubts About Its Value Alarm Many, WASH. POST, Feb. 17, 2002, at A1 (describing the debate prompted by findings that routine screening for breast cancer does not reduce mortality); Laurie Tarkan, In Many Delivery Rooms, a Routine Becomes Less Routine, N.Y. TIMES, Feb. 26, 2002, at F6 (reporting that episiotomies have started to decline in response to research finding no benefits and serious risks associated with this once common procedure during delivery).

219 See Concato, John et al., Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs, 342 NEW ENG. J. MED. 1887, 1890-92 (2000)CrossRefGoogle ScholarPubMed; Feinstein, Alvan R. & Horowitz, Ralph I., Problems in the “Evidence” of “Evidence-Based Medicine”, 103 AM. J. MED. 529 (1997)CrossRefGoogle ScholarPubMed; Knottnerus, Andre & Dinant, Geert Jan, Editorial, Medicine-Based Evidence, a Prerequisite for Evidence-Based Medicine, 315 BRIT. MED. J. 1109 (1997)Google ScholarPubMed; see also Black, Nick, Why We Need Observational Studies to Evaluate the Effectiveness of Health Care, 312 BRIT. MED. J. 1215 (1996)CrossRefGoogle ScholarPubMed (arguing that these research methods can complement one another).

220 See Casarett, David et al., Determining When Quality Improvement Initiatives Should Be Considered Research: Proposed Criteria and Potential Implications, 283 JAMA 2275, 2279-80 (2000)CrossRefGoogle ScholarPubMed; Choo, Vivien, Thin Line Between Research and Audit, 352 LANCET 337, 338 (1998)CrossRefGoogle ScholarPubMed; see also Brett, Allan & Grodin, Michael, Ethical Aspects of Human Experimentation in Health Services Research, 265 JAMA 1854, 1856-57 (1991)CrossRefGoogle ScholarPubMed (discussing the role of informed consent in prospective outcomes research); Rothstein, Mark & Hoffman, Sharona, Genetic Testing, Genetic Medicine, and Managed Care, 34 WAKE FOREST L. REV. 849, 888 n.271 (1999)Google ScholarPubMed (“Such studies would not constitute medical research … but rather, retrospective, records-based outcomes assessment.”).

221 See Taubes, Gary, Epidemiology Faces Its Limits, 269 SCIENCE 164, 165 (1995)CrossRefGoogle ScholarPubMed; see also Allison v. McGhan Med. Corp., 184 F.3d 1300, 1316 (11th Cir. 1999) (“While we acknowledge the importance of anecdotal studies for raising questions and comparing clinicians’ findings, in the face of controlled, population-based epidemiological studies which find otherwise, these case studies pale in comparison.”); Haggerty v. Upjohn Co., 950 F. Supp. 1160, 1165 (S.D. Fla. 1996) (explaining that case reports are “no substitute for a scientifically designed and conducted inquiry”), aff’d mem., 158 F.3d 588 (11th Cir. 1998). See generally KENNETH J. ROTHMAN & SANDER GREENLAND, MODERN EPIDEMIOLOGY (2d ed. 1998).

222 See Levine, Mitchell et al., Users’ Guides to the Medical Literature: IV. How to Use an Article About Harm, 271 JAMA 1615, 1616-17 (1994)CrossRefGoogle ScholarPubMed; Lawrence K. Altman, Risk of Death Found in Use of Heart Drug, N.Y. TIMES, Nov. 1, 1995, at A16. They also may do so in an effort to diagnose patients who contract a mysterious illness, which concurrently produces generalizable knowledge. See Noah, Lars, Pigeonholing Illness: Medical Diagnosis as a Legal Construct, 50 HASTINGS L.J. 241, 249-50, 291-92 (1999)Google Scholar.

223 See Gellin, Bruce G. & Schaffner, William, Editorial, The Risk of Vaccination—The Importance of “Negative” Studies, 344 NEW ENG. J. MED. 372, 372 (2001)CrossRefGoogle ScholarPubMed.

224 See Strom, Brian L. & Tugwell, Peter, Editorial, Pharmacoepidemiology: Current Status, Prospects, and Problems, 113 ANNALS INTERNAL MED. 179 (1990)CrossRefGoogle ScholarPubMed; Temple, Robert, Meta-Analysis and Epidemiologic Studies in Drug Development and Postmarketing Surveillance, 281 JAMA 841, 842-43 (1999)CrossRefGoogle ScholarPubMed.

225 See Capron, A.M., Protection of Research Subjects: Do Special Rules Apply in Epidemiology?, 44 J. CLINICAL EPIDEMIOLOGY 81S, 83S (1991)CrossRefGoogle ScholarPubMed (conceding that, “in most cases, investigators do not intervene physically with the subject and may not even have direct contact of any sort,” but still arguing for consent as a response to concerns about privacy); Dickens, Bernard M., Issues in Preparing Ethical Guidelines for Epidemiological Studies, 19 LAW MED. & HEALTH CARE 175, 176-77 (1991)CrossRefGoogle ScholarPubMed; Greely, Henry T., Breaking the Stalemate: A Prospective Regulatory Framework for Unforeseen Research Uses of Human Tissue Samples and Health Information, 34 WAKE FOREST L. REV. 737, 740 (1999)Google Scholar (“[O]btaining fresh informed consent for new research with previously collected materials has substantial costs.”); Marjorie M. Shultz, Legal and Ethical Considerations in Securing Consent to Epidemiological Research in the United States, in ETHICS AND EPIDEMIOLOGY (Steven S. Coughlin & Tom L. Beauchamp eds., 1996); Snider, Dixie E., Patient Consent for Publication and the Health of the Public, 278 JAMA 624 (1997)CrossRefGoogle ScholarPubMed (criticizing the undue insistence on securing patient consent before publishing research that contains any potentially identifying information); Veatch, Robert M., Editorial, Consent, Confidentiality, and Research, 336 NEW ENG. J. MED. 869, 869 (1997)CrossRefGoogle ScholarPubMed (conceding that the “practice of using patients’ records for research without their explicit consent is widespread”); see also Farnsworth v. Procter & Gamble Co., 758 F.2d 1545, 1546-48 (11th Cir. 1985) (affirming protective order preventing the discovery of the records of individual patients used in an epidemiological study); Wolpin v. Philip Morris Co., 189 F.R.D. 418, 425-30 (C.D. Cal. 1999) (allowing discovery of raw data with individual identifying information redacted); WILLIAM H. ROACH, JR., MEDICAL RECORDS AND THE LAW 123-27 (3d ed. 1998).

226 Even so, federal regulations exempt much of this work. See 45 C.F.R. § 46.101(b)(4) (2001) (exempting “[r]esearch, involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified”); id. § 46.102(f)(2) (defining “human subject” as including someone whose medical records are used by a researcher).

227 See Zeller v. Greater Baltimore Med. Ctr., 506 A.2d 646, 653 (Md. Ct. Spec. App. 1986) (“A record or log of treatment and results is not necessarily an experiment or test.”); cf. N.Y. PUB. HEALTH LAW § 2441(a) (2002) (excluding epidemiological investigations from the definition of “human research”).

228 Woodward, Beverly, Challenges to Human Subject Protections in US Medical Research, 282 JAMA 1947, 1952 (1999)CrossRefGoogle ScholarPubMed (“The expansion of research using a variety of imaging and monitoring devices, human biological materials, and information processing technologies may, before long, turn every patient into a research subject (or rather, research object) simply by virtue of a decision to seek medical care.”).

229 See Mariner, Wendy K., Outcomes Assessment in Health Care Reform: Promise and Limitations, 20 AM. J.L. & MED. 37, 40 (1994)CrossRefGoogle ScholarPubMed (“When properly studied, some commonly accepted medical procedures are found to be of no significant benefit.”) (citing Epstein, Richard et al., Effects of Parenterally Administered Gold Therapy on the Course of Adult Rheumatoid Arthritis, 114 ANNALS INTERNAL MED. 437 (1991)CrossRefGoogle Scholar); see also Schafer, Arthur, The Ethics of the Randomized Clinical Trial, 307 NEW ENG. J. MED. 719, 723 (1982)CrossRefGoogle ScholarPubMed (“If a study of the history of medicine reveals anything, it reveals that clinical judgment without the check of scientific controls is a highly fallible compass.”); Swerdlow, Paul S., Editorial, A Tradition of Testing Ironclad Practices, 267 JAMA 560, 561 (1992)CrossRefGoogle ScholarPubMed (noting “the considerable burden of incorrect information with the status of lore”); Gina Kolata, Questions Raised on Lung Operation, N.Y. TIMES, Aug. 15, 2001, at A1 (describing the initial results of a government-sponsored RCT finding that a popular new surgical intervention for emphysema was ineffective and perhaps dangerous at least for the most critically ill patients).

230 See Guyatt, Gordon H. et al., Users’ Guides to the Medical Literature: II. How to Use an Article About Therapy or Prevention: A. Are the Results of the Study Valid?, 270 JAMA 2598, 2599 (1993)CrossRefGoogle ScholarPubMed; Kunz, Regina & Oxman, Andrew D., The Unpredictability Paradox: Review of Empirical Comparisons of Randomised and Non-Randomised Clinical Trials, 317 BRIT. MED. J. 1185, 1188 (1998)CrossRefGoogle ScholarPubMed; Pocock, Stuart J. & Elbourne, Diana R., Editorial, Randomized Trials or Observational Tribulations?, 342 NEW ENG. J. MED. 1907 (2000)CrossRefGoogle ScholarPubMed. But cf. Benson, Kjell & Hartz, Arthur J., A Comparison of Observational Studies and Randomized, Controlled Trials, 342 NEW ENG. J. MED. 1878, 1884 (2000)CrossRefGoogle ScholarPubMed (finding that they “usually produce similar results”); Ioannidis, John P.A. et al., Comparison of Evidence of Treatment Effects in Randomized and Nonrandomized Studies, 286 JAMA 821, 827 (2001)CrossRefGoogle ScholarPubMed (same).

231 See Gradishar, William J., Editorial, High-Dose Chemotherapy and Breast Cancer, 282 JAMA 1378, 1379 (1999)CrossRefGoogle ScholarPubMed. Similarly, the results of large-scale clinical trials have discredited the widespread and dangerous use of anti-arrhythmia drugs for the prophylactic treatment of acute myocardial infarction. See THOMAS J. MOORE, DEADLY MEDICINE: WHY TEN's OF THOUSANDS OF HEART PATIENTS DIED IN AMERICA's WORST DRUG DISASTER (1995); David Brown, First, Do the Trials. Then, Do No Harm, WASH. POST, Aug. 4, 2002, at B1.

232 See Susan Okie, Hormone Treatment Is Called Harmful, WASH. POST, July 10, 2002, at A1; Susan Okie, Knee Surgery for Arthritis Is Ineffective, Study Finds, WASH. POST, July 11, 2002, at A1.

233 See INSTITUTE OF MEDICINE, SMALL CLINICAL TRIALS: ISSUES AND CHALLENGES 3-4 (Charles H. Evans, Jr. & Suzanne T. Ildstad eds., 2001).

234 See Egger, Matthias & Davey-Smith, George, Meta-Analysis: Potentials and Promise, 315 BRIT. MED. J. 1371 (1997)CrossRefGoogle ScholarPubMed; Khan, Khalid S. et al., The Importance of Quality of Primary Studies in Producing Unbiased Systematic Reviews, 156 ARCHIVES INTERNAL MED. 661 (1996)CrossRefGoogle ScholarPubMed; Moher, David & Olkin, Ingram, Meta-Analysis of Randomized Controlled Trials: A Concern for Standards, 274 JAMA 1962 (1995)CrossRefGoogle ScholarPubMed; Naylor, C. David, Editorial, Meta-Analysis and the Meta-Epidemiology of Clinical Research, 315 BRIT. MED. J. 617 (1997)CrossRefGoogle ScholarPubMed; Sacks, Henry S. et al., Meta-Analyses of Randomized Controlled Trials, 316 NEW ENG. J. MED. 450 (1987)CrossRefGoogle ScholarPubMed; Thacker, Stephen B., Meta-Analysis: A Quantitative Approach to Research Integration, 259 JAMA 1685 (1988)CrossRefGoogle ScholarPubMed.

235 Cf. Ryan, Thomas J., Editorial, Early Revascularization in Cardiogenic Shock—A Positive View of a Negative Trial, 341 NEW ENG. J. MED. 687, 687-88 (1999)CrossRefGoogle ScholarPubMed (noting that one RCT was “underpowered,” in part due to “slow recruitment,” but emphasizing that “different levels of scientific proof are required for regulatory bodies and for clinicians in search of direction”).

236 See U.S. OFFICE OF TECH. ASSESSMENT, ASSESSING THE EFFICACY AND SAFETY OF MEDICAL TECHNOLOGIES 7 (1978); Dubinsky, Michael & Ferguson, John H., Analysis of the National Institutes of Health Medicare Coverage Assessment, 6 INT’L J. TECH. ASSESSMENT IN HEALTH CARE 480, 487 (1990)Google ScholarPubMed (“[I]n almost 80% of the assessments conducted at NIH, the reviewers had to rely on expert opinion because no controlled research evidence was available for their assessment.”); Sage, William M., Regulating Through Information: Disclosure Laws and American Health Care, 99 COLUM. L. REV. 1701, 1774 (1999)CrossRefGoogle ScholarPubMed; see also Capron, Alexander Morgan, Does Assessment of Medical Practices Have a Future?, 82 VA. L. REV. 1623, 1623 (1996)CrossRefGoogle ScholarPubMed (“It is striking that medicine—for all its vaunted love of the scientific method and the biomedical technologies that are the fruits of scientific investigation—has long been remarkably uninterested in systematically studying the effectiveness of much of what the health care system provides to patients.”).

237 See Ellis, Jonathan et al., Inpatient General Medicine Is Evidence Based, 346 LANCET 407, 407, 409 (1995)Google ScholarPubMed (pointing out that if, instead, one asks what portion of patients receive treatments supported by RCTs, the picture is far less gloomy); Gill, P. et al., Evidence Based General Practice: A Retrospective Study of Interventions in One Training Practice, 312 BRIT. MED. J. 819, 819-21 (1996)CrossRefGoogle ScholarPubMed; Michaud, Gaëtane et al., Are Therapeutic Decisions Supported by Evidence from Health Care Research?, 158 ARCHIVES INTERNAL MED. 1665, 1665-67 (1998)CrossRefGoogle ScholarPubMed.

238 See Blustein, Jan & Marmor, Theodore R., Cutting Waste by Making Rules: Promises, Pitfalls, and Realistic Prospects, 140 U. PA. L. REV. 1543, 1549 (1992)CrossRefGoogle ScholarPubMed (“[RCTs] are events of epic proportion, lasting for years, costing millions of dollars, involving thousands of patients, facing monumental bureaucratic barriers, and raising serious ethical issues. Often, by the time clinical trials are completed, the technology they studied is outmoded.” (footnotes omitted)); see also David M. Eddy & John Billings, The Quality of Medical Evidence: Implications for Quality of Care, HEALTH AFF., Spring 1988, at 19, 28; Rabeneck, Linda et al., Problems in the Conduct and Analysis of Randomized Clinical Trials, 152 ARCHIVES INTERNAL MED. 507, 511 (1992)CrossRefGoogle ScholarPubMed (discussing problems that arise during the course of RCTs that make the results more difficult to interpret).

239 See H. DAVID BANTA & BRYAN R. LUCE, HEALTH CARE TECHNOLOGY AND ITS ASSESSMENT: AN INTERNATIONAL PERSPECTIVE 91-92, 283 (1993); Foote, Susan Bartlett, Assessing Medical Technology Assessment: Past, Present, and Future, 65 MILBANK Q. 59, 75-76 (1987)CrossRefGoogle ScholarPubMed.

240 See 60 Fed. Reg. 49,086, 40,095 (1995) (“Clinical equipoise has been described as existing when at least a reasonable minority of medical professionals believe the test article is as good or better than the standard treatment or that the standard treatment to be tested is no better than placebo.”); Freedman, Benjamin, Equipoise and the Ethics of Clinical Research, 317 NEW ENG. J. MED. 141, 143-44 (1987)CrossRefGoogle ScholarPubMed (distinguishing theoretical equipoise, which would require total ambivalence by the individual physician-investigator); Levine, Robert J., Uncertainty in Clinical Research, 16 LAW MED. & HEALTH CARE 174, 174-76 (1988)CrossRefGoogle ScholarPubMed; see also Marquis, Don, How to Resolve an Ethical Dilemma Concerning Randomized Clinical Trials, 341 NEW ENG. J. MED. 691, 692 (1999)CrossRefGoogle ScholarPubMed (concluding that, “because respect for informed consent entails offering a patient the reasonable alternatives to the recommended treatment, and because enrollment in an appropriate randomized clinical trial is often a reasonable therapeutic option,” a physician ambivalent about the standard treatment should leave the choice about opting for participation in an experiment to the patient).

241 See Byar, David P. et al., Design Considerations for AIDS Trials, 323 NEW ENG. J. MED. 1343, 1345 (1990)CrossRefGoogle ScholarPubMed; Clark, Pamela I. & Leaverton, Paul E., Scientific and Ethical Issues in the Use of Placebo Controls in Clinical Trials, 15 ANN. REV. PUB. HEALTH 19, 26-30 (1994)CrossRefGoogle ScholarPubMed; Collier, Joe, Editorial, Confusion over Use of Placebos in Clinical Trials, 311 BRIT. MED. J. 821, 821-22 (1995)CrossRefGoogle ScholarPubMed; Freedman, Benjamin et al., Placebo Orthodoxy in Clinical Research II: Ethical, Legal, and Regulatory Myths, 24 J.L. MED. & ETHICS 252 (1996)CrossRefGoogle ScholarPubMed; Rothman, Kenneth J. & Michels, Karin B., The Continuing Unethical Use of Placebo Controls, 331 NEW ENG. J. MED. 394, 397 (1994)CrossRefGoogle ScholarPubMed; Stein, C. Michael & Pincus, Theodore, Placebo-Controlled Studies in Rheumatoid Arthritis: Ethical Issues, 353 LANCET 400 (1999).CrossRefGoogle ScholarPubMed See generally Hoffman, Sharona, The Use of Placebos in Clinical Trials: Responsible Research or Unethical Practice?, 33 CONN. L. REV. 449 (2001)Google ScholarPubMed. The occasional use of sham surgical procedures has raised some peculiar difficulties. See Freeman, Thomas B. et al., Use of Placebo Surgery in Controlled Trials of a Cellular-Based Therapy for Parkinson's Disease, 341 NEW ENG. J. MED. 988 (1999)CrossRefGoogle ScholarPubMed; Laura Johannes, First Cut: Sham Surgery Is Used to Test Effectiveness of Novel Operations, WALL ST. J., Dec. 11, 1998, at A1.

242 In his substantial body of scholarly work, Jay Katz has provided the most prominent expression of this position. In large measure, Dr. Katz sought to refute the conventional wisdom of his and earlier generations of physicians that “view[ed] human experimentation merely as an extension of medical practice.” Katz, supra note 111, at 411. Fair enough, but perhaps we would also do well to recognize the extent to which medical practice is merely an extension of human experimentation. Not only might this influence approaches to informed consent, but a greater appreciation of the inevitable contingency of medicine appropriately pierces the dogmatism that still prevails in clinical practice.

243 A pair of British researchers recently took a similar approach in order to make the same essential point:

Iain Chalmers & Richard I. Lindley, Double Standards on Informed Consent to Treatment, in INFORMED CONSENT IN MEDICAL RESEARCH 266, 271 (Len Doyal & Jeffrey S. Tobias eds., 2001); see also Geller, Gail et al., Genetic Testing for Susceptibility to Adult-Onset Cancer: The Process and Content of Informed Consent, 277 JAMA 1467, 1468 (1997)CrossRefGoogle ScholarPubMed (“Since informed consent is as important in the clinical setting as it is in research, particular care must be taken by clinicians who do not have the benefit of [IRB] evaluation of their [genetic] testing protocols.”).