Against permititis: Why voluntary organizations should regulate the use of cancer drugs

Minnesota Law Review

Volumn 94, Issue 1, 2010, Pages 1-41

  Epsteint, Richard A ^a  

^a UNIVERSITY OF CHICAGO   (United States)

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[No Author keywords available]

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EID: 79551671224     PISSN: 00265535     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (195)

1. MANCUR OLSON, JR., THE LOGIC OF COLLECTIVE ACTION 14 (1965).
2. Garrett Hardin, The Tragedy of the Commons, 162 SCI. 1243, 1244, 1248 (1968);
3. see also H. Scott Gordon, The Economic Theory of a Common Property Resource: The Fishery, 62 J. POL. ECON. 124, 125-26 (1954).
4. Schloendorff v. Soc'y of N.Y. Hosp., 105 N.E. 92, 93 (N.Y. 1914), abro-gated on other grounds by Bing v. Thunig, 143 N.E.2d 3, 9 (N.Y. 1957), superseded by statute, N.Y. PUB. HEALTH LAW § 2805-d (McKinney 2007), as recognized in Eetkwa v. Orentreich, 584 N.Y.S.2d 710 (N.Y. Sup. Ct. 1992).
5. See Richard A. Epstein, The Erosion of Individual Autonomy in Medical Decisionmaking: Of the FDA and IRBs, 96 GEO. L.J. 559, 566-80 (2008).
6. George J. Annas, Cancer and the Constitution-Choice at Life's End, 357 NEW ENG. J. MED. 408, 410 (2007)
7. See NAT'L COMM'N FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH, ETHICAL PRINCIPLES AND GUIDE-LINES FOR THE PROTECTION OF HUMAN SUBJECTS OF RESEARCH 4-5 (1978);
8. see also Larry R. Churchill, Toward a More Robust Autonomy: Revising the Belmont Report, in BELMONT REVISITED 111, 111 (James F. Childress et al. eds., 2005) (criticizing the Belmont Report's "weak and distorted understanding of self-determination");
9. Richard A. Epstein, Defanging IRBs: Replacing Coercion with Information, 101 Nw. U. L. REV. 735, 741-45 (2007) (discussing the Belmont Report's conceptual errors). For a more critical view on the licensing of research performed on human subjects
10. see Philip Hamburger, Getting Permission, 101 NW. U. L. REV. 405, 406-10 (2007).
11. See DANIEL DEFOE, ROBINSON CRUSOE 234, 302 (Thomas Keymer ed., Oxford 2007) (1719). The original Robinson Crusoe was said to have spent twenty-seven years in isolation on a tropical island located somewhere in the Caribbean
12. Indeed, the Supreme Court has recognized the government's sweeping power to protect the population's health: Nothing in the history of the 1938 Food, Drug, and Cosmetic Act, which first established procedures for review of drug safety, or of the 1962 Amendments, which added the current safety and effectiveness standards in § 201(p)(l), suggests that Congress intended protection only for persons suffering from curable diseases⋯. Both Reports note with approval the PDA's policy of considering effectiveness when passing on the safety of drugs prescribed for "life-threatening disease." United States v. Rutherford, 442 U.S. 544, 552-53 (1979) (footnotes omitted).
13. See, e.g., Michael W. McConnell, Active Liberty: A Progressive Alterna tive to Textualism and Originalism?, 119 HAEV. L. REV. 2387, 2391 (2006) (re viewing STEPHEN BREYER, ACTIVE LIBERTY (2005)) ("The classical liberal tra dition emphasizes limited government, checks and balances, and strong protection of individual rights.").
14. Adam Smith explains the "invisible hand" presumption as follows: [E]very individual necessarily labours to render the annual revenue of the society as great as he can. He generally, indeed, neither intends to promote the public interest, nor knows how much he is promoting it. By preferring the support of domestic to that of foreign industry, he intends only his own security; and by directing that industry in such a manner as its produce may be of the greatest value, he intends only his own gain, and he is in this, as in many other cases, led by an invisible hand to promote an end which was no part of his intention. Nor is it always the worse for the society that it was no part of it. By pursuing his own interest he frequently promotes that of the society more effectually than when he really intends to promote it. I have never known much good done by those who affected to trade for the public good. ADAM SMITH, AN INQUIRY INTO THE NATURE AND CAUSES OF THE WEALTH OF NATIONS 423 (Edwin Cannan ed., Random House, Inc. 1937) (1776).
15. See LAWRENCE O. GOSTIN, PUBLIC HEALTH LAW: POWER, DUTY, RE-STRAINT 16-17 (2008) (discussing broadly the regulation of harmful activities);
16. Mark Hall, The Scope and Limits of Public Health Law, 46 PERSP. BIOL. & MED. S199, S204-05 (Supp. 2003) (discussing the critical role of regulating pollution and contagion specifically). For a rejoinder to Gostin, see Richard A. Epstein, In Defense of the "Old" Public Health: The Legal Framework for the Regulation of Public Health, 69 BROOK. L. REV. 1421, 1425-28 (2004).
17. Cf. Epstein, supra note 4, at 564 (arguing that an autonomous individual is properly defined as one who has an awareness of how his or her actions affect others).
18. See ROBERT D. REID & DAVID C. BOJANIC, HOSPITALITY MARKETING MANAGEMENT 214 (4th ed. 2006) ("[T]rade associations collect information from their members and then provide industry averages that can be used to measure a firm's relative importance.").
19. Cf. Arnold J. Rosoff, Consumer-Driven Health Care: Questions, Cautions, and an Inconvenient Truth, 28 J. LEGAL MED. 11, 24-25 (2007) (suggesting that as consumers become more involved in the healthcare marketplace "there will be increasing pressure on providers to make information available" and "mechanisms of various sorts, governmental and private, will evolve to assure that information is reliable and up to date").
20. See, e.g., AMERICAN CANCER SOCIETY, TREATMENT DECISION TOOLS (2009), http://www.cancer.org/docroot/ETO/eto-lJa.asp7fronrfast/ (providing extensive information about various cancers and available treatments).
21. See, e.g., ALS Worldwide, http://www.alsworldwide.org/ (last visited Oct. 21, 2009) (noting that ALS Worldwide, which deals with amyotrophic lateral sclerosis, or Lou Gehrig's disease, was created by Stephen and Barbara Byer after losing their son to ALS).
22. See Amy P. Abernethy et al., Systematic Review: Reliability of Compendia Methods for Off-Label Oncology Indications, 150 ANNALS INTERNAL MED. 336, 336-37 (2009) (listing the following compendia of cancer treatment information: American Hospital Formulary Service Drug Information, United States Pharmacopeia Drug Information for the Health Professional (now known as " DrugPoints"), DRUGDEX Information System, Drug Facts and Comparisons, NCCN, and Clinical Pharmacology). The databases Abernethy lists are available only for commercial subscribers.
23. One example, the Consortium for Citizens With Disabilities, serves as a clearinghouse of information on a range of health care topics, and is comprised of nearly one hundred member organizations who operate together to advocate for national public policy measures. See Consortium for Citizens With Disabilities, http://www.c-c-d.org (last visited Oct. 21, 2009)
24. Another, the International Lyme and Associated Diseases Society, provides a forum for medical professionals dedicated to the proper diagnosis and treatment of Lyme and its associated diseases through reviewing clinical research programs and providing material, advice, and education for physicians and healthcare providers. See International Lyme and Associated Diseases Society, http://www ilads.org (last visited Oct. 21, 2009).
25. SEE RICHARD A. EPSTEIN, OVERDOSE: HOW EXCESSIVE GOVERNMENT REGULATION STIFLES PHARMACEUTICAL INNOVATION 116-18 (2006).
26. See id.
27. See Richard A. Epstein, Medical Malpractice: The Case for Contract, 1 AM. B. FOUND. RES. J. 87, 94-110, 122, 130 (1976);
28. Richard A. Epstein, The Path to The T.J. Hooper: Of Custom and Due Care, 21 J, LEGAL STUD. 1, 4-5, 19-20 (1992). The distinction is found in many, but by no means all, cases.
29. See, e.g., Holland v. Pitocchelli, 13 N.E.2d 390, 390-91 (Mass. 1938) (noting the distinction);
30. Farwell v. Boston & Worcester R.R., 45 Mass. (4 Met.) 49, 60-61 (1842) (illustrating the distinction's historical use);
31. Pfaffenbach v. White Plains Express Corp., 216 N.E.2d 324, 325-26 (N.Y. 1966) (Burke, J., concurring) (applying the distinction).
32. See generally Richard A. Epstein, A Theory of Strict Liability, 2 J. LEGAL STUD. 151, 166-89 (1973) (discussing the various causal paradigms in stranger cases).
33. See id. at 166-68,177-79.
34. SEE RICHARD A. EPSTEIN, OVERDOSE: HOW EXCESSIVE GOVERNMENT REGULATION STIFLES PHARMACEUTICAL INNOVATION 116-18 (2006).
35. See id.
36. See Richard A. Epstein, Medical Malpractice: The Case for Contract, 1 AM. B. FOUND. RES. J. 87, 94-110, 122, 130 (1976);
37. Richard A. Epstein, The Path to The T.J. Hooper: Of Custom and Due Care, 21 J, LEGAL STUD. 1, 4-5, 19-20 (1992). The distinction is found in many, but by no means all, cases.
38. See, e.g., Holland v. Pitocchelli, 13 N.E.2d 390, 390-91 (Mass. 1938) (noting the distinction);
39. Farwell v. Boston & Worcester R.R., 45 Mass. (4 Met.) 49, 60-61 (1842) (illustrating the distinction's historical use); Pfaffenbach v. White Plains Express Corp., 216 N.E.2d 324, 325-26 (N.Y. 1966) (Burke, J., concurring) (applying the distinction).
40. See generally Richard A. Epstein, A Theory of Strict Liability, 2 J. LEGAL STUD. 151, 166-89 (1973) (discussing the various causal paradigms in stranger cases).
41. See id. at 166-68, 177-79.
42. See Canterbury v. Spence, 464 F.2d 772, 790 (D.C. Cir. 1972) ("[T]he very purpose of the disclosure rule is to protect the patient against consequences which, if known, he would have avoided by foregoing the treatment."). For a discussion of the cross-currents between objective and subjective choices
43. see Peter H. Schuck, Rethinking Informed Consent, 103 YALE L.J. 899, 956-59 (1994).
44. See, e.g., Alex Berenson, 33 States to Get$62 Million in Zyprexa Case Settlement, N.Y. TIMES, Oct. 7, 2008, at B7 (reporting that state-initiated lawsuits against drug company Eli Lilly for improperly marketing the antipsychotic medication Zyprexa netted the largest consumer protection settlement in history)
45. See, e.g., United States v. Rutherford, 442 U.S. 544, 552-53 (1979) (holding that Congress passed the Food, Drug and Cosmetic Act and the 1962 Amendments to the Act in part to shield and protect terminally ill patients).
46. See EPSTEIN, supra note 19, at 116-18.
47. See Brief for John E. Calfee et al. as Amici Curiae Supporting Petitioner at 5, Wyeth v. Levine, 129 S. Ct. 1187 (2009) (No. 06-1249) (explaining that the FDA knows it faces more heat when it commits the visible Type I error of letting bad drugs on the market than the invisible Type II error of keeping good drugs off the market). As a matter of social utility, the two errors are of equal magnitude.
48. See EPSTEIN, supra note 19, at 116-18.
49. See HARVEY TEFF & COLIN MUNRO, THALIDOMIDE: THE LEGAL AF-TERMATH 4-6 (1976).
50. See id. at 122 (documenting President John F. Kennedy's call for increased regulation of drugs in his 1962 State of the Union address in response to thalidomide's dangerous side effects).
51. See, e.g., The International Myeloma Foundation, the MDS Foundation and a Coalition of Patient Advocacy Organizations Call for Updated Rules for Reimbursement, Access and Approvals for New and Existing Cancer Treatments, http://myeloma.org/main.jsp?type=article&id=2651 (outlining a "Statement of Principles" issued on behalf of patients and caregivers demanding that policies for early approval of new cancer treatments be "reformed and streamlined" and that "an efficient and effective mechanism" be created to allow patients to access experimental treatments).
52. See, e.g., Amy Harmon, Fighting for a Last Chance at Life, N.Y. TIMES, May 16, 2009, § 1, at 1 (documenting the struggles of one family's appeal to the FDA for the experimental use of an unapproved drug).
53. See id. ("The F.D.A. itself does not want patients to bypass clinical trials, which require that some patients receive a placebo to determine reliably whether a drug works.").
54. See Alexander Kamb et al., Why Is Cancer Drug Discovery So Difficult?, 6 NATURE REVS. DRUG DISCOVERY 115, 115 (2007) ("Oncology has one of the poorest records for investigational drugs in clinical development, with success rates that are more than three times lower than for cardiovascular diseases.").
55. Sue Kovach, The Abigail Alliance Motivated by Tragic Circumstances, Families Battle an Uncaring Bureaucracy, LIFE EXTENSION (SPECIAL EDI-TION), 2007, at 25, 26.
56. The Abigail Story, http://abigail-alliance.org/story.htm (last visited Oct. 21, 2009).
57. News Release, U.S. Food & Drug Admin., FDA Approves Erbitux for Colorectal Cancer (Feb. 12, 2004), available at http://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/2004/ucml08244.htm.
58. See Jerome Groopman, The Right to a Trial, NEW YORKER, Dec. 18, 2006, at 40, 40 (explaining the formation and goals of the Abigail Alliance).
59. Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 445 F.3d 470, 486 (D.C. Cir. 2006), rev'd en banc, 495 F.3d 695, 713 (D.C. Cir. 2007);
60. see also Epstein, supra note 4, at 574-76.
61. Abigail Alliance, 495 F.3d at 713.
62. 381 U.S. 479 (1965).
63. 521 U.S. 702, 735 (1997).
64. 521 U.S. 793, 797 (1997).
65. See Kovach, supra note 40, at 26-28.
66. See Expanded Availability of Investigational New Drugs Through a Parallel Track Mechanism for People With AIDS and Other HIV-Eelated Disease, 57 Fed. Keg. 13,250, 13,252 (Apr. 15, 1992) (explaining that "parallel track" programs that make investigational drugs accessible only to patients who do not meet the eligibility requirements for a clinical trial will not impair the clinical trial process).
67. See, e.g., United States v. Rutherford, 442 U.S. 544, 558 (1978) (describing how "resourceful entrepreneurs" have historically marketed fraudulent concoctions and treatments to vulnerable patients);
68. see also Corrected En Banc Brief for the Appellees at 35-36, Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 495 F.3d 695 (D.C. Cir. 2007) (No. 04-5350) ("The history of drug use in the nineteenth century is a history of quackery and fraud, of desperate patients throwing away their money and their health on elixirs that did everything except cure diseases and save lives.").
69. For a discussion of ordinary claims against physicians with respect to prescribing drugs, see Lauren Krohn, Cause of Action Against Physician for Negligence in Prescribing Drugs Or Medicines, in 9 CAUSES OF ACTION 1, 6-66 (Wesley H. Winborne ed., 1986).
70. See Abigail Alliance, 495 F.3d at 713.
71. See Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 301 (2006). For an exhaustive discussion of this issue, see Sandra H. Johnson, Polluting Medical Judgment? False Assumptions in the Pursuit of False Claims Regarding Off-Label Prescribing, 9 MINN. J, L. SCI. & TECH. 61, 69-70 (2008).
72. See Daniel B. Klein & Alexander Tabarrok, Do Off-Label Drug Practices Argue Against FDA Efficacy Requirements? A Critical Analysis of Physicians' Argumentation for Initial Efficacy Requirements, 67 AM. J. ECON. & SOC. 743, 750 (2008) ("Of 492 physicians answering the question [of whether the FDA should restrict off-label uses], 460 opposed ending the freedom to prescribe off-label.").
73. See 21 U.S.C. §§ 355(a), 331(d) (2006) (prohibiting marketing unapproved drugs);
74. id. § 352(f) (defining a drug or device as "misbranded" if not properly labeled with directions for its use);
75. See also U.S. FOOD & DRUG ADMIN., GOOD REPRINT PRACTICES FOR THE DISTRIBUTION OF MEDICAL JOURNAL ARTICLES AND MEDICAL OR SCIENTIFIC REFERENCE PUBLICATIONS ON UNAPPROVED NEW USES OF APPROVED DRUGS AND APPROVED OR CLEARED MEDICAL DEVICES (2009), http://www.fda.gov/oc/op/goodreprint.html ("An approved new drug that is marketed for an unapproved use is an unapproved new drug with respect to that use. An approved drug that is marketed for an unapproved use ⋯ is misbranded because the labeling of such drug does not include 'adequate directions for use.'") (citations omitted).
76. Janet Woodcock, A Shift in the Regulatory Approach (June 23, 1997) (on file with the Minnesota Law Review) (PowerPoint presentation outlining the reasons for FDA policies on off-label uses);
77. see also Final Guidance on Industry-Supported Scientific and Educational Activities, 62 Fed. Reg. 64,074, 64,081 (Dec. 3, 1997) (describing how banning promotion of unapproved uses "protect [s] the public health by preserving the integrity of the premarket approval process" and maintains an incentive for manufacturers to conduct clinical investigations, thus "encouraging scientific research and eliminating unnecessary harms to patients");
78. On Biostatistics and Clinical Trial, http://onbiostatistics.blogspot.com/ 2009/02/evidence-based-medicine-evidence-gap.html (Feb. 14, 2009, 15:27 EST) (explaining the FDA's rationale for pro-hibiting promotion of off-label uses). See generally David L. Sackett et al., Evidence Based Medicine: What It Is and What It Isn't, 312 BRIT. MED. J. 71 (1996) (discussing the usefulness of and fears associated with the practice of evidence-based medicine).
79. See Johnson, supra note 54, at 114 (describing how the pharmaceutical company Parke-Davis paid over$455 million as a result of litigation concerning the drug Neurontin). Parke-Davis was a division of Warner-Lambert, which later merged with Pfizer.
80. Id. at 103 n.169.
81. Press Release, U.S. Dep't of Justice, Serono to Pay$704 Million for the Illegal Marketing of AIDS Drug (Oct. 17, 2005), available at http://justice.gov/opa/pr/2005/October/05-civ-545.html. For a discussion of some of the First Amendment issues arising from FDA restriction of pharmaceutical promotion to physicians,
82. see Aaron S. Kesselheim & Jerry Avorn, Pharmaceutical Promotion to Physicians and First Amendment Rights, 358 NEW ENG. J. MED. 1727, 1727-28 (2008).
83. Amaris Elliott-Engel, Drug Companies on the Hook for Off-Label Use of Generic, LEGAL INTELLIGENCER, Mar. 24, 2008, http://www.law.com/jsp/pa/ PubArticlePA.jsp?id=900005506685.
84. See Kovach, supra note 40, at 26-27.
85. See AMERICAN CANCER SOCIETY, COMPASSIONATE DRUG USE (2009), http://www.cancer.org/docroot/ETO/content/ETO-l-2x-Compassionate-Drug-Use.asp
86. See id.(describing requirements for drugs outside of a clinical trial).
87. See Harmon, supra note 37.
88. Id.
89. Id.
90. Id.
91. Id.
92. Id.
93. Id.
94. Id.
95. See MARCIA ANGELL, THE TRUTH ABOUT THE DRUG COMPANIES: HOW THEY DECEIVE US AND WHAT TO DO ABOUT IT 135-55 (2004) (discussing the conflict of interest inherent in drug companies' advertising and educating others about their own products);
96. JEROME KASSIRER, ON THE TAKE: HOW MEDICINE'S COMPLICITY WITH BIG BUSINESS CAN ENDANGER YOUR HEALTH 50-63, 79-103 (2004) (discussing conflicts of interest);
97. Troyen A. Brennan et al., Health Industry Practices that Create Conflicts of Interest: A Policy Proposal for Academic Medical Centers, 295 J. AM. MED. ASS'N 429, 431-32 (2006) (proposing heightened conflict of interest standards). For a critique of strong conflict of interest proposals
98. see Richard A. Epstein, Conflicts of Interest in Health Care: Who Guards the Guardians, 50 PERSP. BIOL. & MED. 72, 83-86 (2007) (asserting that regulators also face conflicts of interest and arguing against overregulating conflicts of interest);
99. Thomas Stossel, Regulation of Financial Conflicts of Interest in Medical Practice and Medical Research: A Damaging Solution in Search of a Problem, 50 PERSP. BlOL. & MED. 54, 67-69 (2007) (attacking overreactions to conflicts of interest).
100. Richard A. Epstein, Op-Ed., Cancer Patients Deserve Faster Access to Life-Saving Drugs, WALL ST. J., May 2, 2009, at Al.
101. Typical of the reaction was Dr. Mark Fesen, who wrote: As an oncologist in private practice, I encounter situations similar to this daily. In our group, we try to aggressively advocate for our patients. The bureaucratic roadblocks that we frequently run into can be deadly serious for patients and disheartening for the staff. One recent case involved a patient who is currently in pain suffering from a metastatic small bowel cancer. The several drugs approved and tested for colon cancer (Avastin, Erbitux, Camptosar, and Oxalip-latinum) have and will not and will not [sic] be tested for this rare type of cancer. Yet it makes intuitive sense to consider using them. Due to the lack of clinical trials studying these drugs in this situation, Medicare will not approve their use. NCCN guidelines, which follow evidence-based medicine and clinical trials, are of little help in this situation. Unfortunately, this patient, along with many others will pass away while suffering from a cancer for which useful treatment is likely very near. My patients' only option is to risk self paying for these expensive drugs. E-mail from Dr. Mark Fesen, M.D., to author (May 3, 2009, 21:26 CDT) (on file with author).
102. Here is one such email: As someone whose first husband died of cancer at age 40 (stomach cancer caught after it had metastasized to the liver), I appreciated your identifying much of what we went through, but I question the implied premise that the FDA should have any role in medicine. For instance, I would like to address your statement: "no one thinks that unapproved cancer drugs should be freely available to patients." We knew that my husband's cancer was in all likelihood terminal, but it would have been far better to have had access to some drugs in the experimental stage than be told, as we were, to join the long waiting list for a clinical trial, which we did. By the time my husband's name moved to the top of the list months later, he was too weak to travel to Texas where the study was being done. He died a few weeks later. From your article, I believe you understand how devastating this situation was to my husband and his family. But if government increases its role in the health care decisions of all Americans, this kind of story will not be a rarity. Advocating "tweaks" in the present system will not suffice; it is the basic idea of government regulating medicine that must be addressed. The answer to our health care situation is to get the government out of the health care business and institute a completely free-market approach, getting rid of mandates and regulations that make the present system less than optimal in some cases, and disastrous in others. I hope you will consider arguments made by people like Paul Hsieh (www.WeStandFirm.org) in your thinking on this subject. E-mail from anonymous reader to author (May 4, 2009, 15:25 CDT) (on file with author).
103. See ABELOFF'S CLINICAL ONCOLOGY, supra note 26, at 1667-80 (describing various prostate cancer treatments).
104. Id. at 361.
105. See id. at 459-81 (discussing chemotherapeutic drugs and their known toxicities, or side effects).
106. See id. at 451.
107. See AMERICAN CANCER SOCIETY, WHAT IS HOSPICE CARE? (2009), http://www.cancer.org/docroot/ETO/content/Eto-2-5x-WhatJs-Hospice-Care.asp ("Hospice care is meant for the time when cancer treatment can no longer help you.").
108. One general conceit states that a human being should be treated as a "six million dollar man." See Kevin Murphy & Robert Topel, Diminishing Returns?: The Costs and Benefits of Improving Health, 46 PERSP. BIOL. & MED. S108, S110-15 (2003) (calculating the value of increasing longevity). There are many complications here, including questions of the sensitivity of the value of life to age and health conditions, but the revealed behavior suggests a high number. The precise number does not matter so long as it is large. But the size of the information gap sets in motion a set of private and public strategies toward data collection that shape the social organization for the provision of cancer treatment. Improve odds by five percent and, as a first approximation, there is substantial social gain, which if not$300,000, is still substantial. See id. at Sill. With error costs high and mistakes common, it makes sense for everyone to invest heavily in knowledge.
109. See, e.g., Robert Cockburn et al., The Global Threat of Counterfeit Drugs: Why Industry and Governments Must Communicate the Dangers, 4 PUB. LlBR. SCI. MED. 302, 302-08 (2005) (discussing why the government has to counteract the risk of counterfeit drugs);
110. Paul M. Rudolf & Ilisa B.G. Bernstein, Counterfeit Drugs, 350 NEW ENG. J. MED. 1384, 1384-86 (2004) (noting the rising incidence of counterfeit drugs). The process has world-wide implications. See Roger Bate, New Tools to Fight Fake Medicines, AM. ENTERPRISE INST, FOR PUB. POL'Y RES., May 13, 2009, http://www.aei.org/article/100492.
111. Mallenbaker.net, Companies in Crisis-What to Do When It All Goes Wrong, http://www.mallenbaker.net/csr/crisis02.html (last visited Oct. 21, 2009) (recounting the response to incidents in 1982 and 1986 when seven people died in Chicago after consuming cyanide-laced Tylenol, causing a loss of one billion dollars in market value after the 1982 incident and spurring wide recalls and the creation of tamper proof packages after the 1986 incident).
112. See U.S. Food & Drug Admin., Is It Really FDA Approved?, http:// www.fda.gov/ForConsumers/ConsumerUpdates/ucm047470.htm#biologics (last visited Oct. 21, 2009) (noting some manufacturers may say their products are "FDA-approved").
113. Cf. Posting of Peter Pitts to DrugWonks.com, http://www.drugwonks .eom/blogjost/show/4755 (Feb. 28, 2008, 10:58 EST) (describing the FDA Commissioner's remarks about how clear FDA communication combats the erosion of consumer trust).
114. See, e.g., American Cancer Society, FDA Approves Advanced Prostate Cancer Drug, Dec. 2, 2003, http://www.cancer.org/docroot/NWS/content/NWS-2-lx-FDA- Approves-Advanced-Prostate-Cancer-Drug.asp (describing a cancer drug that can only be prescribed by a limited number of doctors due to its serious side effects).
115. Recently, the FDA has demanded a "Risk Evaluation and Mitigation Strategy," or "REMS," in some circumstances. That requirement could undermine the present legal framework that allows doctors to make off-label uses of drugs. See U.S. Food & Drug Admin., Questions and Answers on the Federal Register Notice on Drugs and Biological Products Deemed to Have Risk Evaluation and Mitigation Strategies, http://www.fda.gov/ RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/ SignificantAmendments totheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/ ucm095439 .htm (last visited Oct. 21, 2009) (explaining the Identification of Drug and Biological Products Deemed to Have Risk Evaluation and Mitigation Strategies for Purposes of the Food and Drug Administration Amendments Act of 2007, 73 Fed. Eeg. 16,313, at 16,313 (Mar. 27, 2008)).
116. See The Law of Biologic Medicine: Hearing Before the S. Comm. on the Judiciary, 108th Cong. 122-35 (2004) (submission of Lester M. Crawford, Acting Comm'r of Food & Drugs, Dep't of Health & Human Servs.) (noting that faster FDA approval of drugs reduces their cost and increases their availability).
117. See, e.g., PHYSICIANS' DESK REFERENCE 1852 (63d ed. 2009) (describing Prozac as an antidepressant that functions as a selective serotonin reuptake inhibitor (SSRI), which blocks the absorption of serotonin into the blood).
118. See abstract of one study states the following conclusion: SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979. Robert D. Gibbons et al., Early Evidence on the Effects of Regulators' Suicidally Warnings on SSRI Prescriptions and Suicide in Children and Adolescents, 164 AM. J. PSYCHIATRY 1356, 1356 (2007).
119. See Arnold S. Relman, To Lose Trust, Every Day, NEW REPUBLIC, July 23, 2007, at 36, 40 (2007) (reviewing EPSTEIN, supra note 19).
120. Reed Abelson & Andrew Pollack, Medicare Widens Drugs It Accepts for Cancer Care, N.Y. TIMES, Jan. 27, 2009, at Al (discussing new policies regarding the FDA's use of recommendations from voluntary organizations).
121. See id.
122. See NATIONAL TRADE AND PROFESSIONAL ASSOCIATIONS OF THE UNITED STATES, at i-viii (Valerie S. Sheridan ed., Columbia Books, 43d ed. 2008), for a list of over 7600 trade associations in the United States, many of which serve multiple functions.
123. See id. at ii (noting international cooperation).
124. See id. at iii ("Both membership and donor-based organizations are heavily reliant on public trust⋯.").
125. See Abelson & Pollack, supra note 92 (noting the use of alternative references).
126. see id. (giving examples of various sources of information).
127. See id. (describing the funding systems of some groups).
128. See id. (noting the steps taken to control conflicts of interest within committees).
129. See, e.g., American Chronic Pain Association, http://www.theacpa.org/ (last visited Oct. 21, 2009).
130. For an example of one voluntary organization's mission statement, see id.
131. See Abelson & Pollack, supra note 92 (stating that Medicare's new policy of using recommendations from more voluntary organizations is partly in response to concerns that "the agency has been too slow to recognize promising new off-label treatments").
132. See, e.g., Society of Thoracic Surgeons, Welcome to the STS National Database, http://www.sts.org/sections/stsnationaldatabase/ (last visited Oct. 21, 2009).
133. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 352 (2006) (regulating drug labeling);
134. see also United States v. Caronia, 576 F. Supp. 2d 385, 392 (E.D.N.Y. 2008) ("It is well established that under the FDA's 'intended use' regulations, the promotion of a drug for an off-label use by the manufacturer or its representative is prohibited regardless of what directions the manufacturer or representative may give for that use.").
135. See generally Johnson, supra note 54, at 81-83 (discussing some of the difficulties surrounding the regulation of off-label drug use).
136. U.S. Food & Drug Admin., Questions and Answers: Problem Eeporting, http://www.fda.gov/Safety/EeportaProblem/QuestionsandAnswersProblem Reporting/default.htm#problems (last visited Oct. 21, 2009) (noting "medical practice" is not handled by the FDA).
137. See American Cancer Society, Off-Label Drug Use, http://www.cancer.org/ docroot/ETO/content/ETO-l-2x-Off-Label-Drug-Use.asp (last visited Oct. 21, 2009) ("Off-label drug use is very common in cancer treatment.").
138. See Steve Usdin, Regulation: System Reset in 2008, BIOCENTURY, Jan. 21,2008, at A1.A3-A4.
139. See id. (discussing how costs of the clinical trial scheme dissuade drug development).
140. See Sharona Hoffman, The Use of Placebos in Clinical Trials: Responsible Research or Unethical Practice?, 33 CONN. L. REV. 449, 453 (2000).
141. Johnson, supra note 54, at 61 (citations omitted).
142. See Margaret Gilhooley, Drug Preemption and the Need to Reform the FDA Consultation Process, 34 AM. J.L. & MED. 539, 552 (2008) ("Manufacturers are concerned about the limited patent life of their drugs and the need to recoup the considerable cost of drug testing within a limited time frame.").
143. See Miranda Hitti, Thalidomide OK'd for Multiple Myeloma, WEBMD HEALTH NEWS, May 26, 2006, http://www.webmd.com/mental-health/bulimia -nervosa/news/20060526/thalidomide-okd-for-multiple-myeloma.
144. See Abernethy et al, supra note 17, at 336.
145. Id. at 341-42.
146. Interestingly enough, despite her reservations, Dr. Abernethy noted more recently that she did not oppose the new Medicare rules and cited new entry into the market as her reason.
147. See Abelson & Pollack, supra note 92 ("I think the addition of the new compendia this year is an important increase in the bandwidth." (quoting Dr. Abernethy)).
148. National Comprehensive Cancer Network, http://www.nccn.org (last visited Oct. 21, 2009).
149. Press Release, Natl Comprehensive Cancer Network, NCCN Updates Breast Cancer Guidelines (Jan. 22, 2008), available at http://www.nccn.org/about/news/ arehivedjiews.asp (follow "2008" hyperlink; then follow "NCCN Updates Breast Cancer Guidelines" hyperlink).
150. See Richard A. Epstein, The Case for Field Preemption of State Laws in Drug Cases, 103 Nw. U. L. REV. 463, 471 (2009) ("[T]he physician is in the best position to determine if a treatment that is undesirable in some patients is desirable in others & mellip;.").
151. See INST. OF MED. OF THE NAT'L ACADS., THE FUTURE OF DRUG SAFE-TY 31-64 (Alina Bacin et al. eds., 2007) (describing the drug regulatory process).
152. Thus I have been chastised as follows: Does Epstein really not understand that properly designed and conducted clinical trials are now universally accepted as the most reliable means of determining the effectiveness of a drug? & mellip; Clinical trials ⋯changed the basis for the use of drugs from something akin to hearsay and witchcraft to something much closer to science⋯. Relman, supra note 91, at 40.
153. See supra notes 40-42 and accompanying text.
154. EUGENE L. RASOR, WINSTON S. CHURCHILL, 1874-1965, at 261 (2000).
155. F. A. Hayek, Socialist Calculation: The Competitive 'Solution,' 7 ECO-NOMICA 125, 125-27 (1940);
156. F. A. Hayek, The Use of Knowledge in Society, 35 AM. ECON. REV. 519, 524 (1945). For my approach to limited knowledge, see generally Richard A. Epstein, Intuition, Custom, and Protocol: How to Make Sound Decisions with Limited Knowledge, 2 N.Y.U. J.L. & LIBERTY 1 (2006) (discussing how intuition, custom, and protocol create knowledge) and Richard A. Epstein, The Uses and Limits of Local Knowledge: A Cautionary Note on Hayek, 1 N.Y.U. J.L. & LIBERTY 205 (2005) (contrasting local and formal knowledge).
157. See Prescription Drug User Fee Amendments of 2007, Pub. L. No. 110-85, 121 Stat. 823, 825-42 (codified as amended at 21 U.S.C.A. §§ 379g-379j (West Supp. 2009)).
158. David A. Kessler & David C. Vladeck, A Critical Examination of the FDA's Efforts to Preempt Failure-to-Warn Claims, 96 GEO. L.J. 461, 472 (2008);
159. see also INST. OF MED. OF THE NATL ACADS., supra note 120, at 193 ("There is little dispute that the FDA in general is ⋯severely underfunded.").
160. See SUBCOMM. ON SCI. & TECH., FDA SCI. BD., FDA SCIENCE AND MISSION AT RISK 22 (2007).
161. Id. at 6.
162. Matthew Borghese, Obama's Budget Expands FDA's Food, Medicine Safety Funding, May 12, 2009, ALL HEADLINE NEWS, http://www.all headlinenews.com/ articles/7015110502 ("Obama's budget will give an additional 19 percent in funding to the FDA's two major projects; protecting America's food supply and ensuring safer medical products.").
163. Cf. U.S. Food & Drug Admin., How Drugs are Developed and Approved,
164. News Release, U.S. Food & Drug Admin., FDA Proposes Guidance for Dissemination of Information on Unapproved Uses of Medical Products (Feb. 15, 2008), available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ 2008/ucmll6859.htm (recommending that distribution be limited to peer-reviewed journals with editorial boards that have conflict of interest policies);
165. see Anna Wilde Mathews & Avery Johnson, Boost for Off-Label Drug Use: FDA Would Let Firms Keep Doctors Informed on Unapproved Methods, WALL. ST. J., Feb. 16, 2008, at A3 (reporting on the FDA proposal).
166. See Mathews & Johnson, supra note 131.
167. See ABELOFF'S CLINICAL ONCOLOGY, supra note 26, at 327-35 (describing several opportunities for physicians and patients to participate in clinical trials and the review process for clinical trials).
168. See Jeanne Lenzer, Drug Secrets: What the FDA Isn't Telling, SLATE, Sept. 25, 2005, http://www.slate.com/id/2126918/ (noting that even if a drug is already on the market for different uses, trade secret concerns may lead drug companies to not divulge results from failed clinical trials that have adverse events).
169. In general, I support the publication of trade secret information needed to evaluate serious health risks. That also seems to be the general principle in Corn Products Refining Co. v. Eddy, which stated: [I]t is too plain for argument that a manufacturer or vendor has no constitutional right to sell goods without giving to the purchaser fair information of what it is that is being sold. The right of a manufacturer to maintain secrecy as to his compounds and processes must be held subject to the right of the State, in the exercise of its police pow-er and in promotion of fair dealing, to require that the nature of the product be fairly set forth. 249 U.S. 427, 431-32 (1919).
170. This rationale clearly applies to drugs that might have harmful effects; however, similar disclosures of trade secrets should not be applied when these risks of adulteration, misbranding, or danger to health are not present. See Bichard A. Epstein, The Constitutional Protection of Trade Secrets Under the Takings Clause, 71 U. CHI. L. REV. 57, 61-73 (2004) (discussing which risks should be disclosed and why that raises hard questions of implementation).
171. See Andrew Pollack, Wider Use of Avastin Is Approved, N.Y. TIMES, Feb. 23, 2008, at CI (discussing the increase in share values after Avastin's approval);
172. see also Marilyn Chase & Anna Wilde Mathews, Genentech Clears Hurdle on Cancer Drug Avastin, WALL ST. J., Feb. 23-24, 2008, at A3 (report ing on Avastin's approval)
173. See Tomas J. Philipson & Anupam B. Jena, Who Benefits from New Medical Technologies? Estimates of Consumer and Producer Surpluses for HIV/AIDS Drugs, 9 P. FOR HEALTH ECON. & POL% issue 2, art. 3, at 16 (2006), http://www.bepress.eom/fliep/biomedicaLresearch/3/ (noting that even with unregulated prices, drug innovators could only capture about five percent of the social surplus through innovation).
174. See id. at 1 (noting that, in the aggregate, there is a$1.33 trillion dollar consumer surplus in the total lifetime value of H1V/A1DS drugs).
175. Cf. Eichard A. Epstein, The Permit Power Meets the Constitution, 81 IOWA L. EEV. 407, 414-19 (1995) (discussing how permit systems currently operate).
176. See id. at 414.
177. SEE SUBCOMM. ON SCI. & TECH., FDA SCI. BD., FDA SCIENCE AND MISSION AT RISK: ESTIMATED RESOURCES REQUIRED FOR IMPLEMENTATION 8-9 (2008), available at http://energycommerce.house.gov/Press-110/022508 .ScienceBoardReport. EstimatedResources.pdf (noting that the "FDA lacks information technology (IT) capability and capacity to support monitoring of drug and food safety and is particularly challenged in the regulation of products based upon new science").
178. See, e.g., Project Inform: Mission Statement, http://www.projectinform .org/about/mission.shtml (last visited Oct. 21, 2009) ("Project Inform ⋯supports individuals to make informed choices about their HIV health ⋯.").
179. See Steve Usdin, FDA Reviewing Intellectual Bias, BIOCENTURY, Apr. 20,2009, at All.
180. See EPSTEIN, supra note 19, at 137 ("The PDA deals only in averages, and the averages don't predict the response of any one individual to either drug." (quoting Steven Walker, Letter to the Editor, Iressa: The Reality vs. the FDA's Version, WALL ST. J., July 26, 2005, at A25)).
181. See id. at 135-38.
182. See Victoria Colliver, New Option for Breast Cancer Treatment, S.F. CHRON., Feb. 23, 2008, at Al (noting that approval was granted in the absence of any other treatment for metastatic breast cancer).
183. See FDA Panel Nixes Avastin for Breast Cancer, http://www .pharmalot.com/2007/12/fda-panel-nixes-avastin-for-breast-cancer(Dec.5, 2007, 16:36 EST) (noting that PDA medical reviewers found that the slower rate of tumor progression did not offset the increase in side effects).
184. See Heather Tomlinson, The FDA Feared Throughout the Pharmaceutical Industry, INDEPENDENT, Aug. 12, 2001, http://www.independent.co .uk/news/business/news/the-fda-feared-throughout-the-pharmaceutical-industry- 665420.html (discussing the negative impact of an FDA rejection on a drug company's share prices).
185. See Pollack, supra note 136 (reporting that women went a median of 11.3 months before their cancer worsened or they died when they used Avastin in combination with Taxol, compared with 5.8 months if they just took Taxol).
186. See id.
187. See Schuck, supra note 29, at 924-25
188. See, e.g., Alicia Mundy, Dingell, Grassley Call for Overhaul of Agency 'Culture,' WALL ST. J., July 30, 2008, at A4 (reporting that reforms proposed by Senator Grassley and Eepresentative Dingell, aimed at increasing the PDA's effectiveness, would give the FDA the power to levy fines, expanded power to order drug recalls, and the authority to impose additional limitations on drug advertisements);
189. see also Press Release, Charles E. Grassley, Ranking Member, U.S. Senate Comm. on Fin., Grassley Asks for an Accounting of Contacts Between FDA and Device Maker (Mar. 6, 2009), available at http:// finance.senate.gov/press/ Gpress/2009/prg030609d.pdf (noting what Grassley deems "a 'too cozy relationship' between the FDA and industry").
190. See Usdin, supra note 108, at A2.
191. Luis M. B. CABRAL, INTRODUCTION TO INDUSTRIAL ORGANIZATION 112 (2000) (noting that duopoly prices are lower than monopoly prices).
192. See Editorial, The Regulator Disapproves, NATURE BIOTECH., Jan. 2008, at 1, 1 (discussing the FDA's decision to delay approval of the cancer vaccine Provenge, calling it a "knee-jerk defensive response to accusations of process impropriety").
193. See id.
194. See id. Advisory committees are composed of experts in a given field to advise the FDA on whether and how to approve certain types of drugs. See U.S. Food & Drug Admin., Advisory Committees, http://www.fda.gov/ AdvisoryCommittees/default.htm (last visited Oct. 21, 2009) (discussing the composition of FDA advisory committees)
195. See The Regulator Disapproves, supra note 155, at 1.