The money blind: How to stop industry bias in biomedical science, without violating the first amendment

American Journal of Law and Medicine

Volumn 37, Issue 2-3, 2011, Pages 358-387

  Robertson, Christopher T ^a  

^a UNIVERSITY OF ARIZONA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; ECONOMICS; HUMAN; INDUSTRY; INTERPERSONAL COMMUNICATION; LEGAL ASPECT; MEDICAL RESEARCH; PEER REVIEW; PUBLISHING; UNITED STATES;

BIOMEDICAL RESEARCH; DISCLOSURE; HUMANS; INDUSTRY; PEER REVIEW, RESEARCH; PUBLICATION BIAS; PUBLISHING; UNITED STATES;

EID: 80051854902     PISSN: 00988588     EISSN: None     Source Type: Journal    
DOI: 10.1177/009885881103700207     Document Type: Review

References (189)

1. E. Ray Dorsey et al., Funding of US Biomedical Research, 2003-2008, 303 JAMA 137, 142 (2010).
2. (citing Gail R. Wilensky, Developing a Center for Comparative Effectiveness Information, 25 Health Aff. w572 (2006)).
3. See Marc-Andre Gagnon & Joel Lexchin, The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States, 5 PLoS Med. 29, 32 n.4 (2008).
4. See, e.g., Thompson v. W. States Med. Ctr., 535 U.S. 357 (2002) (overturning certain regulations that pertained to prescription drug compounding as unconstitutional restrictions on commercial speech).
5. See, e.g., IMS Health Inc. v. Sorrell, 630 F.3d 263, 267 (2d Cir. 2010) (holding that a Vermont statute violated the First Amendment by restricting prescribing information available to manufacturers who used such information to send "detailers" to influence physicians), cert, granted, 131 S. Ct. 857 (2011).
6. Adriane Fugh-Berman & Douglas Melnick, Off-Label Promotion, On-Target Sales, 5 PLoS Med. 1432, 1433 (2008).
7. Richard Smith, Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies, 2 PLoS Med. 364 (2005).
8. Dan Wikler, A Crisis in Medical Professionalism: Time for Flexner II, in Ethics and the Business of Biomedicine 249, 251 (Denis G. Arnold ed., Cambridge Univ. Press, 2009) (compiling this and other sources cited below).
9. Barton Moffatt & Carl Elliott, Ghost Marketing: Pharmaceutical Companies and Ghostwritten Journal Articles, 50 Persp. Biology & Med. 18, 19 (2007)
10. (quoting a document that was produced in Motus v. Pfizer, 358 F.3d 659 (9th Cir. 2004)).
11. See generally Thomas O. McGarity & Wendy E. Wagner, Bending Science: How Special Interests Corrupt Public Health Research (2008) (describing ways in which scientific processes are corrupted by special interests).
12. Richard S. Irwin, The Role of Conflict of Interest in Reporting of Scientific Information, 136 Chest 253, 254 (2009) (writing as the former editor-in-chief of the journal).
13. Richard Horton, The Dawn of McScience, 51 N.Y. Rev. Books, Mar. 11, 2004, at 9.
14. In re Zyprexa Prods. Liab. Litig. 253 F.R.D. 69, 106 (E.D.N.Y. 2008)
15. rev'd, UFCW Local 1776 v. Eli Lilly & Co., 620 F.3d 121 (2d Cir. 2010) (reversing on the question of causation).
16. H. Moses III et al., Financial Anatomy of Biomedical Research, 294 JAMA, 1333, 1333 (2005).
17. Justin E. Bekelman et al, Scope and Impact of Financial Conflicts of Interest in Biomedical Research: A Systematic Review, 289 JAMA 454, 454 (2003).
18. D. E. Zinner, Participation of Academic Scientists in Relationships with Industry,. Health Aff. 6, at 1814-25 (2009) (explaining further the financial conflicts of interest present in biomedical research).
19. Thomas Bodenheimer, Uneasy Alliance-Clinical Investigators and the Pharmaceutical Industry, 342 New Eng. J. Med. 1539, 1539 (2000).
20. Susannah L. Rose et al., Relationships Between Authorship Contributions and Authors' Industry Financial Ties Among Oncology Clinical Trials, 28 J. Clinical Oncology 1316, 1316 (2010).
21. Alex Wayne, GOP Budget Cuts Likely to Hurt Research, NIH Says, Wash. Post, Nov. 9, 2010, available at http://www.washingtonpost.com/wp-dyn/content/ article/2010/ll/09/AR2010110906764.html.
22. Institute of Medicine, Board on Health Sciences Policy, Conflict of Interest in Medical Research, Education, and Practice 104 (2009) [hereinafter IOM Report].
23. Su Golder & Yoon K. Loke, Is There Evidence for Biased Reporting of Published Adverse Effects Data in Pharmaceutical Industry-Funded Studies?, 66 Brit. J. Clinical Pharmacology 767, 767 (2008).
24. Laurence Hirsch, Conflicts of Interest, Authorship, and Disclosures in Industry-Related Scientific Publications: The Tort Bar and Editorial Oversight of Medical Journals, 84 Mayo Clinic Proc. 811, 812 (2009) (discussing evidence that these discrepancies may be due to publication bias, i.e., the industry's self-censoring of unfavorable results).
25. Mark Friedberg et al., Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology, 282 JAMA 1453, 1455 (1999).
26. Joanna K. Sax, Protecting Scientific Integrity: The Commercial Speech Doctrine Applied to Industry Publications, 37 Am. J.L. & Med. 203 (2011).
27. J. E. Bekelman, Y. Li & C.P. Gross, Scope and Impact of Financial Conflicts of Interest in Biomedical Research: A Systematic Review, 289 JAMA 454, 454-65 (2003). (Pubitemid 36119966)
28. Joel Lexchin et al., Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review, 326 Brit. Med. J. 1167 (2003) (showing that, over the course of multiple studies, research funded by drug companies was more likely to have outcomes favoring the sponsor than studies with non-drug company sponsors).
29. Shahryar Noordin et al., Relationship Between Declared Funding Support and Level of Evidence, 92 J. Bone & Joint Surgery Am. 1647, 1647 (2010).
30. For this distinction in another context, see Caperton v. A.T. Massey Coal Co., 129 S. Ct. 2252, 2266 (2009), observing "[o]ne must also take into account the judicial reforms the States have implemented to eliminate even the appearance of partiality.
31. Christopher T. Robertson, Blind Expertise, 85 N.Y.U. L. Rev. 174, 178 n.ll (2010).
32. (quoting John H. Langbein, The German Advantage in Civil Procedure, 52 U. Chi. L. Rev. 823, 836 (1985)).
33. Marcia Angell, Industry-Sponsored Clinical Research: A Broken System, 300 JAMA 1069, 1070-71 (2008). Angell goes on to say: "It is self-evidently absurd to look to investor- owned companies for unbiased evaluations of their own products. Yet many academic investigators and their institutions pretend otherwise, and it is convenient and profitable for them to do so.".
34. Section 801 of the Food and Drug Administration Act of 2007 does require researchers to register interventional clinical trials and, for marketed products, to disclose the results of such trials within twelve months after study completion, on www.clinicaltrials.gov.
35. See Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85, 121 Stat. 823 (to be codified in scattered sections of 21 U.S.C.). Following several state laws, as of 2013, federal law will also require the industry to disclose its financial relationships with physicians, though there are questions about the completeness and accuracy of such disclosures.
36. Charles Ornstein & Tracy Weber, Drug Companies' Reports Aren't Always Accurate, Star-Trib., Dec 12, 2010, available at http://www.startribune.com/ business/lll704609.html(discussing an analysis of Minnesota's required disclosures).
37. UFCW Local 1776 v. Eli Lilly & Co., 620 F.3d 121 (2d Cir. 2010) (holding that even if plaintiff could prove misrepresentations, it would be unable to prove a causal effect on the prices paid for drugs).
38. Aaron Kesselheim, Off-Label Drug Use and Promotion: Balancing Public Health Goals and Commercial Speech, 37 Am. J.L. & Med. 225, 241 tbl.l (2011) (reviewing DOJ enforcement actions). 28130 S. Ct. 1784 (2010). 29.
39. Claire Bombardier et al., Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis, 343 New Eng. J. Med. 1520, 1526 (2000).
40. Gregory D. Curfman et al., Editorial, Expression of Concern: Bombardier et al., Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis, 353 New Eng. J. Med. 2813, 2813-14 (2005). (Pubitemid 43016825)
41. Merck, 130 S. Ct. 1784. There are also a variety of less prominent interventions. JAMA, for example, requires independent statistical analysis of industry-sponsored studies.
42. Arturo Casadevall & Ferric C. Fang, Editorial, 77 Infection & Immunity 1273 (2009) (editor-in-chief of the journal, weighing the argument that peer review is censorship).
43. Catherine D. DeAngelis, Editorial, The Influence of Money on Medical Science, 8 JAMA 996, at 996-98 (2006) (arguing that certain studies were valid because they survived peer review, even though there were improprieties in the process of disclosing financial relationships with industry). Peer reviewers are often not provided with the authors' financial disclosures. (Pubitemid 44285379)
44. Catherine D. DeAngelis et al., Editorial, Reporting Financial Conflicts of Interest and Relationships Between Investigators and Research Sponsors, 286 JAMA 89, 90 (2001). This policy is apparently intended to preserve the anonymity of the authors, so that the reviewers do not succumb to personal biases, pro or con. Some journals are moving towards a single- blind review, in part to allow reviewers to assess conflicts of interests.
45. Richard Smith, Peer Review: A Flawed Process at the Heart of Science and Journals, 99 J. Royal Soc'y Med. 178, 179 (2006).
46. sources cited supra Part I.B.I.
47. The Supreme Court tells a similar story in the context of mandatory disclosures for political campaign finance. Citizens United v. FEC, 130 S. Ct. 876, 916 (2010) (asserting that a disclosure mandate "enables the electorate to make informed decisions and give proper weight to different speakers and messages").
48. Lloyd Hitoshi Mayer, Disclosures about Disclosure, 44 Ind. L. Rev. 255 (2010) (drawing on psychological literature to criticize this assumption as being too simplistic).
49. Such "off-label" prescribing is quite common and is perfectly legal; physicians can prescribe a drug for any indication as long as the drug has been approved for one indication.
50. Joshua B. Tennenbaum et al., Theory-Based. Bayesian Models of Inductive Learning and Reasoning, 10 Trends Cognitive Sci. 309 (2006) (describing Bayesian reasoning).
51. We are simply assuming, for the sake of argument, that a 0.5 estimate of the likelihood of efficacy is the threshold for a doctor prescribing the drug off-label. In reality, the threshold could be higher or lower, given the risks, costs, and benefits of the drug compared to alternative courses of treatment.
52. Christopher T. Robertson, Biased Advice, Emory L.J. (forthcoming 2011) (an experimental study showing that disclosures of conflicting interests only helped laypersons when laypersons also had access to unconflicted advice).
53. Samena Chaudhry et al., Does Declaration of Competing Interests Affect Readers' Perceptions? A Randomised Trial, 325 Brit. Med. J. 1391, 1392 (2002).
54. Sara Schroter et al., Does the Type of Competing Interest Statement Affect Readers' Perceptions of the Credibility of Research? Randomised Trial, 328 Brit. Med. J. 742 (2004) (finding similar results with multiple papers and testing both stock ownership and research grants disclosures).
55. Dennis F. Thompson, Understanding Conflicts of Interest, 329 New Eng. J. Med. 573, 575 (1993) (arguing that "[a] deficiency of disclosure is that those who receive the information may not know how to interpret it and may not in any case have reasonable alternative courses of action in the circumstances").
56. Kevin A. Kerber & A. Mark Fendrick, The Evidence Base for the Evaluation and Management of Dizziness, 16 J. Evaluation Clinical Pract. 186, 189 (2010) (concluding that "[p]hysicians rely on the medical literature to inform decisions, but our study suggests that the evidence base for dizziness evaluation and management is weak").
57. David M. Eddy, Variations in Physician Practice: The Role of Uncertainty, 3 Health Aff. 74 (1984) (arguing that the practice of medicine is permeated by profound uncertainty about the comparative effectiveness of treatment options).
58. Gabriel K. Silverman et al., Failure to Discount for Conflict of Interest When Evaluating Medical Literature: A Randomised Trial of Physicians, 36 J. Med. Ethics 265, 265-70 (2010).
59. Adam Licurse et al., The Impact of Disclosing Financial Ties in Research and Clinical Care: A Systematic Review, 170 Archives Internal Med. 675, 681 (2010) (providing a literature review and concluding that "these disclosures appear to have a limited effect on behavioral outcomes").
60. Bonnie E. Glaser & Lisa A. Bero, Attitudes of Academic and Clinical Researchers Toward Financial Ties in Research: A Systematic Review, 11 Sci. & Engineering Ethics 553 (2005) (also reviewing this literature).
61. Jared A. Blum et al., Requirements and Definitions in Conflict of Interest Policies of Medical Journals, 302 JAMA 2230 (2009).
62. Jeffrey M. Drazen et al., Uniform Format for Disclosure of Competing Interests in ICMJE Journals, 361 New Eng. J. Med. 1896, 1896 (2009).
63. Kevin P. Weinfurt et al., Consistency of Financial Interest Disclosures in the Biomedical Literature: The Case of Coronary Stents, PloS ONE, May 7, 2008, available at http://www.plosone.Org/article/info:doi/l0.137l/journal.pone. 0002128.
64. Roy M. Pitkin et al., Accuracy of Data in Abstracts of Published Research Articles, 281 JAMA 1110, 1110-11 (1999) (finding that 18-68% of abstracts (varying by journal) include findings "that are inconsistent with or absent from the article's body . . . even in large- circulation general medical journals"). There is a debate about what information should be included in biomedical abstracts, and how they can be made more accurate. (Pubitemid 29155888)
65. Ad Hoc Working Group for Critical Appraisal of the Medical Literature, A Proposal for More Informative Abstracts of Clinical Articles, 106 Annals Internal Med. 598, 598-604 (1987).
66. Scott T. Weiss & Jonathan M. Samet, An Assessment of Physician Knowledge of Epidemiology and Biostatistics, 55 J. Med. Educ. 692, 697 (1980) ("[P]hysicians may not be prepared adequately to evaluate medical literature").
67. Bailey Kuklin, Probability Misestimates in Medical Care, 59 Ark. L. Rev. 527, 537 (2006) (discussing physicians' difficulties with statistical reasoning).
68. Sally Hopewell, Better Reporting of Randomized Trials in Biomedical Journal and Conference Abstracts, 34 J. Info. Sci. 173 (2008) (suggesting that physicians form their first impressions of articles based on the abstracts).
69. Amos Tversky & Daniel Kahneman, Judgment Under Uncertainty: Heuristics and Biases, 185 Science 1124, 1128 (1974) (describing research on the anchoring effect).
70. For other research suggesting disclosure policies, Mark A. Rodwin, Physicians' Conflicts of Interest: the Limitations of Disclosure, 321 New Eng. J. Med. 1405, 1405-08 (1989). (Pubitemid 19284199)
71. Baruch A. Brody et al., Expanding Disclosure of Conflicts of Interest: The Views of Stakeholders, 25 IRB: Ethics & Hum. Res. 1, 1-8 (2003).
72. Roger S. Foster, Conflicts of Interest: Recognition, Disclosure, and Management, 196 J. Am. Coll. Surgeons 505, 505-15 (2003).
73. Michael S. Jellinek, IRBs and Pharmaceutical Company Funding of Research, 4 IRB: Ethics & Hum. Res. 9 (1982).
74. Ron Roizen, Why I Oppose Drug Company Payment of Physician/Investigators on a Per Patient/Subject Basis, 10 IRB: Ethics & Hum. Res. 9, 9-10 (1988).
75. Howard M. Spiro, Mammon and Medicine: The Rewards of Clinical Trials, 255 JAMA 1174, 1174 (1986).
76. Heidi P. Forster et al., The 2000 Revision of the Declaration of Helsinki: A Step Forward or More Confusion?, 358 Lancet 1449, 1449-53 (2001). (Pubitemid 33055755)
77. Kenneth J. Rothman, Conflict of Interest: The New McCarthyism in Science, 269 JAMA 2782, 2782-84 (1993). (Pubitemid 23154255)
78. Daylian M. Cain, George Loewenstein & Don A. Moore, The Dirt on Coming Clean: Perverse Effects of Disclosing Conflicts of Interest, 34 J. Legal Stud. 1, 18 (2005)
79. Ming Li & Kristof Madarasz, When Mandatory Disclosure Hurts: Expert Advice and Conflicting Interests, 139 J. Econ. Theory 47, 48-50, 60, 62-63 (2008).
80. This dynamic is similar to that documented by behavioral researchers in which imposition of a fine for a given behavior actually caused the frequency of that behavior to increase.
81. Uri Gneezy & Aldo Rustichini, A Fine is a Price, 29 J. Legal Stud. 1 (2000).
82. Sergio Sismondo, Ghost Management: How Much of the Medical Literature Is Shaped Behind the Scenes by the Pharmaceutical Industry?, 4 PLoS Med. 1429, 1429 (2007) (quoting Alex Berenson, Evidence in Vioxx Suits Shows Intervention by Merck Officials, N.Y. Times Apr. 24, 2005, available at http://www.nytimes.com/ 2005/04/24/business/24drug.html. 61.
83. David H. Freeman, Lies, Damned Lies, and Medical Science, Atlantic Monthly, Nov. 2010, at 80, available at http://www.theatlantic.com/magazine/ archive/2010/ll/lies-damned-lies-and-medical-science/8269/(quoting John Ioannidis). 6a.
84. Arthur Schafer, Biomedical Conflicts Of Interest: A Defence of the Sequestration Thesis - Learning From the Cases of Nancy Olivieri and David Healey, 30 J. Med. Ethics 8, 23 (2004). 63.
85. John P. A. Ioannidis, Why Most Published Research Findings Are False, 2 PLoS Med. 0696, 0696 (2005).
86. David L. Sackett, Bias in Analytic Research, 32 J. Chronic Diseases 51, 51-63 (1979) (describing some of these sources of bias).
87. Lisa A. Bero & Drummond Rennie, Influences on the Quality of Published Drug Studies, 12 Int'l J. Tech. Assess. Health Care 209, 209-37 (1996) (also describing some sources of bias). (Pubitemid 26195521)
88. D. Michael Risinger et al., The Daubert/Kumho Implications of Observer Effects in Forensic Science: Hidden Problems of Expectation and Suggestion, 90 Cal. L. Rev. 1, 18 (2002) (reviewing the behavioral research literature).
89. William M. Sage, Some Principles Require Principals: Why Banning "Conflicts of Interest" Won't Solve Incentive Problems in Biomedical Research, 85 Tex. L. Rev. 1413, 1448-49 (2007) (arguing for more direct regulation of privately funded biomedical research).
90. Robert Rosenthal, How Often Are Our Numbers Wrong?, 33 Am. Psychologist 1005, 1007 (1978).
91. D. Michael Risinger, The NAS/NRC Report on Forensic Science: A Glass Nine-Tenths Full (This Is About the Other Tenth), 50 Jurimetrics J. 21 (forthcoming 2011), available at http://ssrn.com/abstract=1437276 (discussing similar problems and potential solutions in the forensic science field).
92. TMJ Implants, Inc. v. Aetna, Inc., 498 F.3d 1175, 1195 (10th Cir. 2007) (recognizing that the double-blind study is the gold standard in medicine).
93. Grade Working Group, Grading Quality of Evidence and Strength of Recommendations, 328 Brit. Med. J. 1, 2 (2004) (explaining that reviewers assessing the quality of a study "may state that failure to blind patients and physicians reduced the quality of evidence for an intervention's impact on pain severity and that they considered this a serious limitation"). 68.
94. David P. Byar et al., Design Considerations for AIDS Trials, 323 New Eng. J. Med. 1343, 1345 (1990) ("Blinding is especially desirable when subjective end points, such as pain, functional status, or quality of life, are studied, because such evaluations are open to substantial bias.").
95. In some contexts, it is simply not feasible to require single or double blinding. For example, in the testing of surgical techniques or medical devices, both the surgeon and the patient may need to know what is being done.
96. Lars Noah, Medicine's Epistemology: Mapping the Haphazard Diffusion of Knowledge in the Biomedical Community, 44 Ariz. L. Rev. 373, 391 (2002) (describing these limits).
97. Alternatively, following on the "double blind" model, this method could be called a "triple blind." Alas, the term has already been deployed for other purposes. Triple Blind, Dorland's Medical Dictionary for Health Consumers (2007), available at http://medical-dictionary. thefreedictionary.com/triple+blind (defining "triple blind" as "pertaining to clinical trial other experiment in which neither the subject nor the person administering the treatment nor the person evaluating the response to treatment knows which subjects are receiving a particular treatment or lack of treatment").
98. Sheldon Krimsky, Science in the Private Interest: Has the Lure of Profits Corrupted Biomedical Research? 229 (2003).
99. Marcia Angell, The Truth About the Pharmaceutical Industry: How They Deceive Us and What to Do About It 245 (2004) (calling for an independent drug evaluation agency within the NIH).
100. Troyen A. Brennan et al., Health Industry Practices That Create Conflicts of Interest: A Policy Proposal for Academic Medical Centers, 295 JAMA 429, 432 (2006) ("To promote scientific progress, [Academic Medical Centers] should be able to accept grants for general support of research (no specific deliverable products) from pharmaceutical and device companies, provided that the grants are not designated for use by specific individuals. As long as the institution stands between the individual investigator and the company making the grant, the likelihood of undue influence is minimized but certainly not eliminated").
101. Nat'l Inst, of Health, Research Project Grants & Other Mechanisms: Competing Applications, Awards, Success Rates, and Total Funding Made with Direct Authority and Superfund Funds, by NIH Institutes/Center, Grant Mechanisms, and Activity Codes, NIH Res. Portfolio Online Reporting Tools (Dec. 17, 2010), http://report.nih.gov/FileLink.aspx?rid=601.
102. Nat'l Inst, of Health, Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC), NIH Res. Portfolio Online Reporting Tools, http://report.nih.gov/rcdc/categories/(table data as of Mar. 15, 2011).
103. HHS Evaluation and Disposition of Applications, 42 C.F.R. § 52.5(b) (2010).
104. Grassetti v. Weinberger, 408 F. Supp. 142, 151 (N.D. Cal. 1976).
105. U.S. Gov't Accountability Office, Food and Drug Administration: FDA Faces Challenges Meeting its Growing Medical Product Responsibilities and Should Develop Complete Estimates of Its Resource Needs 16 (2009), available at http://www.gao.gov/new.items/d0958l.pdf.
106. Early Consultation, 21 C.F.R. § 312.82 (2010) (encouraging drug makers to work with regulators "to review and reach agreement on the design" of studies before they are carried out).
107. Sanket S. Dhruva et al., Strength of Study Evidence Examined by the FDA in Premarket Approval of Cardiovascular Devices, 302 JAMA 2679, 2682 tbl.l (2009).
108. Discussion supra Part I.B.3.
109. Dean Keith Simonton, Scientific Genius: A Psychology of Science 5, 42 (1990) (discussing Thomas Kuhn's recognition of an "essential tension" between the "traditionalist" and the "iconoclast" roles of a scientist and F. C. Bartlett's differentiation between "original and routine information processing").
110. Indeed, the industry already outsources much of these routine testing functions to contract research organizations, the key is simply to break the yoke of influence over them.
111. generally Phillip Mirowski & Robert Van Horn, The Contract Research Organization and the Commercialization of Scientific Research, 35 Soc. Stud. Sci. 503 (2005) (describing this trend). 87.
112. thank Larry Lessig for this insight.
113. David Willman, Ex-NIH Director Now Favors Limiting Drug Company Ties, L.A. Times, Mar. 13, 2004, http://articles.latimes.com/2004/mar/13/nation/na- nihl3.
114. Curt D. Furberg et al., The FDA and Drug Safety: A Proposal for Sweeping Changes, 166 Archives Internal Med. 1938, 1940 (2006) ("Another problem may relate to the source of FDA funding. Critics of the FDA have claimed that the agency has gotten too close to the industry it is supposed to regulate, in part because of its dependence on user fees. Indeed, each of the past 3 iterations of the Prescription Drug User Fee Act has required that the FDA produce or perform something of value to the pharmaceutical industry in exchange for which the industry would agree to pay the fees. Until the last iteration, the FDA was prohibited from using any funds from user fees to support postmarketing studies of safety.").
115. Gwendolyn B. Emerson & James D. Heckman, Testing for the Presence of Positive- Outcome Bias in Peer Review, 170 Archives Internal Med. 1934, 1936 (2010) (showing positive-outcome bias in a randomized trial with peer reviewers for two journals).
116. Winand Emons, Credence Goods and Fraudulent Experts, 28 RAND J. Econ. 107, 107 (1997) (providing a skeptical analysis of a similar market for advice); Gillian
117. Hadfield et al., Information-Based. Principles for Rethinking Consumer Protection Policy, 21 J. Consumer Pol'y 131, 144 (1998) ("The complex nature of information also requires careful analysis of the potential for market mechanisms to provide the information consumers might want and need. Information is a notoriously difficult commodity over which to contract. Potential buyers of information have difficulty determining, in their uninformed state, the value of the information and thus the price they are willing to pay for it."). 82.
118. Debbie Sieber et al., Extent and Nature of Advertising in Leading Hematology- Oncology Journals, 32 Am. J. Clinical Oncology 92, 92-93 (2009) (citing sources that the industry spent $850 million on journal advertising in 2005).
119. David Orentlicher & Michael K. Hehir, Advertising Policies of Medical Journals: Conflicts of Interest for Journal Editors and Professional Societies, 27 J.L. Med. & Ethics 113, 114 (1999) (discussing the conflicts of interest inherent in the practice of accepting industry money, and discussing journal editors' feelings and expressions of gratitude).
120. Journals that Have Requested Inclusion on the List of Publications that Follow the ICMJE's Uniform Requirements for Manuscripts Submitted to Biomedical Journals, Int'l Comm. of Med. Journal Editors, http://www.icmje.org/journals. html (last visited Apr. 4, 2011) (listing journals).
121. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication, Int'l Comm. of Med. Journal Editors (Apr. 2011) http://www.icmje.org/urm-full.pdf (providing the policy).
122. Natasha Singer, Stanford Medical School to Expand Ethics Rules, N.Y. Times, Mar. 21, 2010, at B3, available at http://www.nytimes.com/2010/03/22/ health/policy/22docs.html (describing a new prohibition on adjunct faculty "giving paid speeches drafted by the makers of drugs or medical devices").
123. School of Medicine Policy Overview, Stanford School of Medicine, http://med.stanford.edu/coi/overview.html (last visited Apr. 14, 2011).
124. John Dorschner, Investigators Question Drug-Makers Payments to University of Miami Doctors, Miami Herald, Dec. 20, 2010, http://www.miamiherald.com/2010/ l2/20/l982509/investigators-question-drug-makers.html#ixzzl8lCuiADQ ("Stanford was the lead example [of non-compliance with its own policy], with two doctors earning more than $100, 000 in the past year for making speeches paid for by drug companies, even though Stanford forbids its faculty from taking such fees.").
125. Jef Akst, Contract Research on the Rise, The Scientist (Aug. 5, 2009), available at http://www.the-scientist.com/blog/display/55878/(describing the history of this industry and its recent changes).
126. Nat'l Inst, of Health, NIH Grants Policy Statement, NIH Office of Extramural Research, § 4.1.3 exhibit 4, http://grants.nih.gOv/grants/ policy/nihgps-2010/nihgps-ch4.htm#public-policy-requirements-other-mandates (last visited Apr. 4, 2011).
127. Basic HHS Policy for Protection of Human Research Subjects: To What Does this Policy Apply?, 45 C.F.R. § 46.101 (2008) (known as "the Common Rule").
128. Intangible Property, 45 C.F.R. § 74.36 (2008) (giving the government the right to publish data and requiring recipient to publish data after Freedom of Information Act requests).
129. 500 U.S. 173, 191 (1991).
130. In this situation, journals would likely become specialized, some accepting industry- funded papers without the money blind and others accepting NIH-funded, foundation-funded, and money-blinded papers (if any). This outcome may be better than the status quo, if it helps consumers of science more appropriately weigh their reliance on the studies they read, using the journal's name as a proxy for scientific objectivity. Nonetheless, the following analysis presumes that regulators want to go further to cause a more complete shift to money-blinding.
131. Health Resources and Services Admin., The Health Center Program: Summary of Key Health Center Program Requirements, http://bphc.hrsa.gov/about/ requirements.htm (last visited Apr. 7, 2011) ("Health centers are non-profit private or public entities . . .").
132. The Office of Minority Health, Non-Profit Organizations, http://minorityhealth.hhs.gov/templates/browse.aspx?lvl=2&lvlID=2(last visited Apr. 7, 2011) ("Only public or nonprofit private institutions of higher learning may apply for training grants ....").
133. 40 C.F.R. § 50.605 (2010).
134. Rumsfeld v. Forum for Academic & Inst. Rights, Inc. (FAIR), 547 U.S. 47, 58 (2006) ("Either allow military recruiters the same access to students afforded any other recruiter or forgo certain federal funds.").
135. 10 U.S.C.A. § 983(b) (West 2011). The Solomon Amendment was repealed in early 2011.
136. Rumsfeld v. Forum for Academic and Institutional Rights, Inc. (FAIR), 547 U.S. at 60.
137. Grove City College v. Bell, 465 U.S. 555, 575 (1984). In Grove City, the Supreme Court rejected a private college's claim that conditioning federal funds on its compliance with Title IX of the Education Amendments of 1972 violated the First Amendment, without even reaching the First Amendment claims, because the school was free to decline federal money.
138. Citizens United v. FEC, 130 S. Ct. 876 (2010) (holding that corporations have free speech rights).
139. Buckley v. Valeo, 424 U.S. 1, 19 ("A restriction on the amount of money a person or group can spend on political communication during a campaign necessarily reduces the quantity of expression by restricting the number of issues discussed, the depth of their exploration, and the size of the audience reached. This is because virtually every means of communicating ideas in today's mass society requires the expenditure of money.").
140. In Boy Scouts of America v. Dale, 530 U. S. 640 (2000), the Supreme Court held that the Boy Scouts' freedom of expressive association was violated by a state law that required the organization to accept a homosexual scoutmaster. The pattern in Boy Scouts was thus the opposite of the present proposal, which prohibits certain associations. Regardless of that distinction, the Boy Scouts holding is likely inapposite to the proposed policy for the same reason that the Court distinguished the case.
141. Kathleen Sullivan, Unconstitutional Conditions, 102 Harv. L. Rev. 1413, 1421 (1989).
142. United States v. Am. Library Ass'n, Inc., 539 U.S. 194, 210 (2003) (quoting Bd. of Cnty. Comm'rs, Wabaun.
143. Cnty. v. Umbehr, 518 U.S. 668, 674 (1996) (internal quotation marks omitted).
144. Perry v. Sindermann, 408 U.S. 593, 597 (1972) ("[I]f the government could deny a benefit to a person because of his constitutionally protected speech or associations, his exercise of those freedoms would in effect be penalized and inhibited. This would allow the government to 'produce a result which [it] could not command directly.' Such interference with constitutional rights is impermissible.").
145. 468 U.S. 364, 381 (1984).
146. 518 U.S. 668, 678 (1996). The Court wrote that the plaintiff "is correct that if the Board had exercised sovereign power against him as a citizen in response to his political speech, it would be required to demonstrate that its action was narrowly tailored to serve a compelling governmental interest. But in this case, as in government employment cases, the Board exercised contractual power, and its interests as a public service provider, including its interest in being free from intensive judicial supervision of its daily management functions, are potentially implicated. Deference is therefore due to the government's reasonable assessments of its interests as contractor."
147. citing Connick v. Myers, 461 U.S. 138, 146 (1983)). It is not precisely clear where speech about the effectiveness of a drug would fall on this spectrum.
148. Rumsfeld v. Forum for Academic & Inst. Rights, Inc. (FAIR), 547 U.S. 47, 59 (2006).
149. Kordel v. United States, 335 U.S. 345, 348-50 (1948) (adopting an expansive definition of "accompanying material" to many forms of industry communications about their products).
150. 21 C.F.R. § 202.1(a)(1) (expanding this definition further to encompass virtually all efforts to promote the product).
151. Gregory Conko, Truth or Consequences: The Perils and Protection of Off-Label Drug and Medical Device Promotion, 21 Health Matrix (forthcoming 2011) (Competitive Enterprise Institute, Working Paper No. 2010-9, 2010), available at http://papers.ssrn.com/sol3/papers.cfm?abstract-id=l677609 (describing and criticizing this regulatory evolution).
152. 21 C.F.R. § 202.1(a)(1) (2010) (regulating industry sponsored CME programs). The FDA's rationale for this broad regulatory power rests on the statutory requirement that labels must describe the product's intended use, and that industry efforts to promote another use suggest that the product is mislabeled in the first place.
153. 62 Fed. Reg. at 64, 075 ("The 'intended use' of a drug or device refers to the objective intent of the persons legally responsible for the labeling of the product. This intent is determined by such persons' expressions or by the circumstances surrounding the distribution of the article including, for example, labeling claims, advertising matter, or oral or written statements by such persons or their representatives.").
154. citing 21 C.F.R. § 201.128 (2010).
155. 21 C.F.R. § 801.4 (2006).
156. Alberty Food Prods. Co. v. United States, 185 F.2d 321 (9th Cir. 1950) (drug product was misbranded because its labeling failed to state the intended use of the drug as suggested by the company in newspaper advertisements)).
157. Coleen Klasmeier & Martin H. Redish, Off-Label Prescription Advertising, the FDA, and the First Amendment: A Study in the Values of Commercial Speech Protection, 37 Am. J.L. & Med. 315, 343 (2011) (arguing that the FDA's analysis is flawed because companies always know that their products will be used off-label, and thus such off-label promotion proves nothing).
158. Klasmeier and Redish seem to assume that knowledge is necessarily equivalent to intent, but the distinction is routinely made throughout the law.
159. Holder v. Humanitarian Law Project, 130 S. Ct. 2705, 2718 (2010) (distinguishing between knowledge and intent in another context: "Congress plainly spoke to the necessary mental state for a violation of § 2339B, and it chose knowledge about the organization's connection to terrorism, not specific intent to further the organization's terrorist activities").
160. United States v. Delgado, 631 F.3d 685, 695 (5th Cir. 2011) ("It is axiomatic that more is required than mere knowledge of the purpose of a conspiracy.").
161. FDA, Final Guidance on Industry-Supported Scientific and Educational Activities; Notice, 62 Fed. Reg. at 64, 074 (Dec. 3, 1997).
162. Supra Part II.A.
163. FDA, Final Guidance on Industry-Supported Scientific and Educational Activities; Notice, 62 Fed. Reg. at 64, 083 (referring to CME providers).
164. Robert Steinbrook, Financial Support of Continuing Medical Education, 299 JAMA 1060, 1062 (discussing a solution of "eliminating direct or indirect commercial support of programs but allowing contributions to a central repository of funds, which, in turn, would disburse funds to approved programs").
165. Cent. Hudson Gas & Elec. Corp. v. Pub. Serv. Comm'n, 447 U.S. 557, 563-64 (1980) (citations omitted).
166. United States v. Caronia, 576 F. Supp. 2d 385, 395 (E.D.N.Y. 2008) (discussing whether "promotional activities amounted to scientific and academic speech, which resides at the core of the First Amendment").
167. Nathan Cortez, Can Speech by FDA-Regulated Firms Ever Be Noncommercial? 37 Am. J.L. & Med. 388 (2011) (arguing that the answer to his titular question "is yes, but only if the stars align"). Arguably, industry- funded science could be regulated through blinding even if it was not deemed commercial speech.
168. Christopher J. Truffer et al., Health Spending Projections Through 2019: The Recession's Impact Continues, 29 Health Aff. 522, 522 (2010) (reporting that the health share of the gross domestic product was estimated at 17-3% in 2009).
169. Whitaker v. Thompson, 248 F. Supp. 2d 1, 9 (D.D.C. 2002) ("Under the Central Hudson analysis, it is 'clear that if the Government could achieve its interest in a manner that does not restrict speech, or that restricts less speech, the Government must do so.™).
170. citing Thompson v. W. States Med. Ctr., 535 U.S. 357, 371 (2002)).
171. 18 U.S.C. § 201(b) (1962) (setting forth conduct constituting bribery and related fines).
172. 18 U.S.C. § 666(a)(2) (2004) (also describing conduct constituting bribery).
173. 41 U.S.C. § 52(2) (2009) (defining "kickback").
174. Kathleen Clark, Financial Conflicts of Interest In and Out of Government, at 6 (2011), available at http://ssrn.com/abstract=1785520 ("If a government employee advises the government on how to handle a matter that could affect her own investments, she could end up in prison. A criminal statute prohibits government employees from participating in matters that can have a direct and predictable effect on their own financial interests.").
175. United States v. Marchetti, 466 F.2d 1309, 1314 (4th Cir. 1972) ("Threats and bribes are not protected simply because they are written or spoken; extortion is a crime although it is verbal").
176. United States v. Meachum, No. 08-3082 Slip Copy, 2009 WL 1255520, at *8 (W.D. Va. May 7, 2009) (same).
177. Roberts v. State, 278 S.W.3d 778, 790 (Tex. App. 2008) (same).
178. Bulletin Displays, LLC v. Regency Outdoor Advertising, Inc., 448 F. Supp. 2d 1172, 1184 (C.D. Cal. 2006) ("[C]ampaign contributions made 'with a corrupt intent to influence ... the person to whom it is given, in his action, vote, or opinion, in any public or official capacity' are not protected because they are not a 'valid' exercise of one's constitutional rights of free speech or petition").
179. (quoting Paul for Council v. Ricki Hanyecz, 85 Cal. App. 4th 1356, 1366-67 (2001)); United States v. Tutein, 82 F. Supp. 2d 442, 447 (D. Virgin Is. 2000) ("[A] private party has no First Amendment right to petition the Government by means of. . . payment of bribes").
180. (quoting In re Airport Car Rental Antitrust Litig., 474 F. Supp. 1072, 1087 (N.D. Cal. 1979)).
181. Dawkins v. State, 208 So.2d 119, 124 (Fla. Dist. Ct. App. 1968) ("One cannot threaten, intimidate, bribe, or otherwise imminently seek to affect the outcome of grand or petit jury deliberations and then seek refuge in the First Amendment. . .").
182. United States v. Hutson, 843 F.2d 1232, 1235 (9th Cir. 1988) ("extortionate speech ... is undoubtedly within the government's power to prohibit").
183. United States v. Quinn, 514 F.2d 1250, 1268 (5th Cir. 1975), cert, denied, 424 U.S. 955 (1976) ("It may categorically be stated that extortionate speech has no more constitutional protection than that uttered by a robber while ordering his victim to hand over the money, which is no protection at all").
184. People v. Hickman, 988 P.2d 628, 636-38 (Colo. 1999) (rejecting a First Amendment attack on a statute making it a crime to threaten a witness, so long as "threat" is limited to "expressions of intent to commit harm or injury to another's person, property, or rights through commission of an unlawful act").
185. State v. Lance, 721 P.2d 1258, 1264-65, 1267 (Mont. 1986) (rejecting a First Amendment attack on a statute making it a crime to threaten to kidnap or unlawfully restrain any person).
186. 18 U.S.C § 1346 (2008) (proscribing honest services fraud).
187. Skilling v. United States, 130 S. Ct. 2896 (2010) (construing the statute to cover only bribes and kickbacks, and arguing that the vague statute borrows content from the federal bribery statutes-which otherwise apply only to federal officials-or state officials who receive federal grant funds). I am not arguing here that the honest services statute actually criminalizes industry payments to independent biomedical researchers, though that argument would be provocative, given the seemingly limitless scope of the honest services fraud statute, even after Skilling.
188. For an explanation of the doctrine.
189. Kent Greena walt, Speech, Crime, and the Uses of Language 249 (1989) (arguing that "[m]y basic position is that such utterances are genuinely situation-altering. They do not inform the listener about the environment he or she inhabits; they change that environment by generating options which did not previously exist and which would never have existed had it not been for the offer or threat. Because they do something rather than say something, they fall outside a principle of free speech."). More accurately, an offer of a bribe both does something (create an incentive) and says something (notify of the incentive).