Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs

Lexchin J. , “Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review,” BMJ 326, no. 31 (2003): 1167–1170; Steinman M. A. , “Characteristics and Impact of Drug Detailing for Gabapentin,” PLoS Medicine 4, no. 4 (2007): 743–751; Hill K. P. , “The ADVANTAGE Seeding Trial: A Review of Internal Documents,” Annals of Internal Medicine 149, no. 4 (2008): 251–258; Ross J. S. , “Guest Authorship and Ghostwriting in Publications Related to Rofecoxib,” JAMA 299, no. 15 (2008): 1800–1812; Sismondo S. , “How Pharmaceutical Industry Funding Affects Trial Outcomes: Causal Structures and Responses,” Social Science & Medicine 66, no. 9 (2008): 1909–1914; Spurling G. , “Information from Pharmaceutical Companies and the Quality, Quantity and Cost of Physicians' Prescribing: A Systemiatic Review,” PLoS Medicine 7, no. 10 (2010): E1000352; Lexchin J. , “Those Who Have the Gold Make the Evidence: How the Pharmaceutical Industry Biases the Outcomes of Clinical Trials of Medications,” Science and Engineering Ethics 18, no. 2 (2012): 247–261; Vedula S. Li T. Dickersin K. , “Differences in Reporting of Analyses in Internal Comany Documents Versus Published Trial Reports: Comparisions in Industry-Sponsored Trials in Off-Label Uses of Gabapentin,” PLoS Medicine 10, no. 1 (2013): E1001378.

Thompson D. , “Two Concepts of Corruption,” in Working Papers ( Safra Edmond J. Center for Ethics: Harvard University, 2010); Lessig L. , Republic, Lost: How Money Corrupts Congress - and a Plan to Stop It (New York: Twelve/Hachette, 2011); Thompson D. , Ethics in Congress: From Individual to Institutional Corruption (Washington, D.C.: Brookings Institution, 1984); see also Lessig L. , “Institutional Corruptions,” in Research in Action Working Papers, Safra Edmond J. Center for Ethics (Cambridge, MA: Research in Action Working Papers, Safra Edmond J. Center for Ethics, Harvard University, 2013). Quotations are from Republic, Lost.

See Republic, Lost, supra note 2, at 285.

Light D. W. , “Strengthening the Theory of Institutional Corruptions: Broadening, Clarifying, Measuring,” in Research in Action Working Paper, Lessig L. Somos M. , eds. ( Safra Edmond J. Center for Ethics: Harvard University, 2013).

Salter M. , “Lawful but Corrupt: Gaming and the Problem of Institutional Corruption in the Private Sector,” in Harvard Business School Working Papers (Boston: Harvard Business School, 2009).

Beauchamp T. Childress J. , Principles of Bioethical Ethics, 5th ed. (New York: Oxford University Press, 2001); Gillon R. , “Medical Ethics: Four Principles Plus Attention to Scope,” BMJ 309, no. 6948 (1994): 184.

See Purposeful Identity, “Merck & Company,” available at <http://www.purposefulidentity.com/values-mission-value-drivers-vision/mission-statement-2011/Merck-Healthcare-Support-Services-industry-104.html> (last visited June 20, 2013). Missions of Pfizer and other companies can be found at the website as well.

JFor a discussion of the misalignment between market incentives and public health goals, and ways to address that problem, see Gagnon M.-A. , “Corruption of Pharmaceutical Markets: Addressing the Misalignment of Financial Incentives and Public Health,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 571–580. See also in JLME 41, no. 3 (2013): Rodwin M. , “Five Un-Easy Pieces to Pharmaceutical Policy Reform,” 581–589, and Sismondo S. , “Key Opinion Leaders and the Corruption of Medical Knowledge: What the Sunshine Act Will and Won't Cast Light On,” 635–643.

See Republic, Lost, supra note 2, at 107–116.

King M. Bearman P. , “Conflict of Interest Policies and the Diffusion of Stimulant, Antidepressant, and Antipsychotic Medications,” in American Sociological Association (New York City: Yale University School of Management, 2013).

Young J. H. , The Toadstool Millionaires: A Social History of Patent Medicines in America before Federal Regulation (Princeton, NJ: Princeton University Press, 1961); Hilts P. J. , Protecting America's Health: The FDA, Business and One Hundred Years of Regulation (New York: Alfred A. Knopf, 2003).

See Hilts , supra note 11; Zelenay J. , “The Prescription Drug User Fee Act: Is a Faster Food and Drug Administration Always a Better Food and Drug Administration?” Food and Drug Law Journal 60, no. 2 (2005): 261–338.

Angell M. , The Truth About the Drug Companies: How They Deceive Us and What to Do About It (New York: Random House, 2004); Avorn J. , Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs (New York: Knopf, 2004); Goozner M. , The $800 Million Pill: The Truth Behind the Cost of New Drugs (Berkeley: University of California Press, 2004).

Light D. Lexchin J. , “Pharmaceutical R&D - What Do We Get for All That Money?” BMJ 344, no. 7869 (2012): e4348.

Light D. W. Lexchin J. , “Foreign Free Riders and the High Price of US Medicines,” BMJ 331, no. 7522 (2005): 958–960; National Science Foundation, “Research and Development in Industry: 1999” (Arlington: March 2002).

Gagnon M.-A. Lexchin J. , “The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States,” PLoS Medicine 8, no. 1 (2008): 1–5.

Prescrire Editorial Staff, “Drugs in 2001: A Number of Ruses Unveiled,” Prescrire International 11, no. 58 (2002): 58–60.

Prescrire Editorial Staff, “New Drugs and Indications in 2011,” Prescrire International 21, no. 126 (2012): 106–110.

Lexchin J. , “International Comparison of Assessments of Pharmaceutical Innovation,” Health Policy 105, nos. 2–3 (2012): 221–225.

See Light Lexchin , supra note 14.

O'Reilly E. , “IND Preparation and Maintenance,” Duke Translational Medicine Institute, available at <http://tracs.unc.edu/docs/regulatory/IND_Presentation-IND_Preparation_and_Maintenance-Best_Practices.ppt> (last visited June 20, 2013); Schmid E. Smith D. , “Is Declining Innovation in the Pharmaceutical Industry a Myth?” Drug Discovery Today 10, no. 15 (2005): 1031–1039.

Steinman M. A. , “Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents,” Annals of Internal Medicine 145, no. 4 (2006): 284–293; Hoffman M. , “Pharmaceutical Detailing Is Not for Everyone,” Journal of Legal Medicine 33, no. 3 (2012): 381–397; Spurling G. , “Information from Pharmaceutical Companies and the Quality, Quantity and Cost of Physicians' Prescribing: A Systemiatic Review,” PLoS Medicine 7, no. 10 (2010): e1000352; see also Sah S. Fugh-Berman A. , “Physicians under the Influence: Social Psychology and Industry Marketing Strategies,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 665–672.

See Avorn , supra note 13, at Chapter 13; Morgan S. G. , “‘Breakthrough’ Drugs and Growth in Expenditure on Prescription Drugs in Canada,” BMJ 331, no. 7520 (2005): 815–816.

See Light Lexchin , supra note 14.

See Avorn , supra note 13, at 205, 197–216.

Lazarou J. Pomeranz B. H. Corey P. N. , “Incidence of Adverse Drug Reactions in Hospitalized Patients,” Journal of American Medical Association 279, no. 15 (1998): 1200–1205.

Other recent studies find similar rates of harm. van der Hooft C. , “Adverse Drug Reaction Related Hospitalizations,” Drug Safety 29, no. 2 (2006): 161–168; Pirmohamed M. , “Adverse Drug Reactions as Cause of Admission to Hospital: Prospecive Analysis of 18,820 Patients,” BMJ 329, no. 7456 (2004): 15–19.

ISMP, “QuarterWatch,” Moore T. J. Cohen M. R. Furberg C. D. , eds. (Horsham, PA: Institute for Safe Medication Practices, 2012).

Lexchin J. , “New Drugs and Safety: What Happened to New Active Substances Approved in Canada between 1995 and 2010?” Archives of Internal Medicine 172, no. 21 (2012): 1680–1681.

Kaiser Family Foundation, Prescription Drug Trends, 2010.

Moore T. , Prescription for Disaster (New York: Simon & Schuster, 1998); Goodnough A. Zezima K. , “Drivers on Prescription Drugs: Dangerous, but Hard to Convict,” New York Times, July 25, 2010.

See Avorn , supra note 13.

Gagnon M.-A. Lexchin J. , “The Cost of Pushing Pills: A New Estimate of pharmaceutical promotion expenditures in the United States,” PLoS Medicine 5, no. 1 (2008); Applbaum K. , “Getting to Yes: Corporate Power and the Creation of a Psychopharmaceutical Blockbuster,” Culture, Medicine and Psychiatry 33, no. 2 (2009): 185–215; Applbaum K. , “Is Marketing the Enemy of Pharmaceutical Innovation?” Hastings Center Report 39, no. 4 (2009): 13–17. For excellent overviews of how dependency corruption compromises the medical profession's duty to make patients as healthy as they can be, see Rodwin M. , “Conflicts of Interest, Institutional Corruption, and Pharma: An Agenda for Reform,” Journal of Law, Medicine & Ethics 40, no. 3 (2012): 511–522; Rodwin M. , “Reforming Pharmaceutical Industry-Physician Financial Relationships: Lessons from the United States, France, and Japan,” Journal of Law, Medicine & Ethics 39, no. 4 (2011): 662–670.

See Young , supra note 11; Hilts , supra note 11.

See Hilts , supra note 11, at 79–90.

Id., at 151–156.

Salter , supra note 5; Salter M. , Short-Termism at Its Worst, Safra Edmond J. Center for Ethics Working Paper No. 5, 2013, available at <http://papers.ssrn.com/sol3/papers.cfm?abstract_id=2247545> (last visited June 20, 2013); Salter M. , Innovation Corrupted: The Origins and Legacy of Enron's Collapse (Cambridge, MA: Harvard University Press, 2008); Carpenter D. , Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA (Princeton: Princeton University Press, 2010).

See Hilts , supra note 11, at Chap. 8. This is about what Prescrire has found since 1981 (Figure 1).

See Republic, Lost, supra note 2, at 107–116.

See Hilts , supra note 11, at Chap. 11.

Food and Drug Administration, “Guidance for FDA Staff and Industry: Marketed Unapproved Drugs: Compliance Policy Guide,” September 19, 2011, at 3, 10–11.

See Hilts , supra note 11; Carpenter , supra note 37.

Id. (Hilts); Abraham J. , Science, Politics and the Pharmaceutical Industry (London: Routledge, 1995); Rodwin M. , “Independent Clinical Trials to Test Drugs: The Neglected Reform,” St. Louis Law Review 6, no. 113 (2012): 113–166.

U.S. Government Accounting Office, “New Drug Approvals: FDA Needs to Enhance its Oversight of Drugs Approved on the Basis of Surrogate Endpoints,” Washington, D.C., 2009; Avorn J. , “Approval of a Tuberculosis Drug Based on a Paradoxical Surrogate Measure,” JAMA 309, no. 13 (2013): 1349–1350.

Garattini S. Bertele V. , “Non-Inferiority Trials Are Unethical Because They Disregard Patients' Interests,” The Lancet 370, no. 9602 (2007): 1875–1877.

Garattini S. Bertele V. , “Efficacy, Safety, and Cost of New Anticancer Drugs,” BMJ 325, no. 7358 (2002): 269–271; Garattini S. Bertele V. , “Ethics in Clinical Research,” Journal of Hepatology 51, no. 4 (2009): 792–797; Garattini S. Bertele V. , “Europe's Opportunity to Open Up Drug Regulation,” BMJ 340, no. 30 (2010): 842–843; Fisher J. A. , Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials (New Brunswick: Rutgers University Press, 2009); Fisher J. A. , “United States Private-Sector Physicians and Pharmaceutical Contract Research: A Qualitative Study,” PLoS Medicine 9, no. 7 (2012): E1001271; McGoey L. , “On the Will to Ignorance in Bureaucracy,” Economy and Society 36, no. 2 (2007): 212–235.

Zimmerman M. Mattia J. Posternak M. A. , “Are Subjects in Pharmacologocal Treatment Trials of Depression Representative of Patients in Routine Clinical Practice,” American Journal of Psychiatry 159, no. 3 (2002): 469–473; Travers J. , “External Validity of Randomised Controlled Trials in Asthma: To Whom Do the Resuls of the Trials Apply?” Thorax 62, no. 3 (2007): 219–223.

Applbaum K. , “Is Marketing the Enemy of Pharmaceutical Innovation?” The Hasting Center Report 39, no. 4 (2009): 13–17; Sismondo S. , “Ghost Management,” PLoS Medicine 4, no. 9 (2007): 1429–1433; see Sismondo , supra note 8; Hart B. Lundh A. Bero L. , “Effect of Reporting Bias on Meta-Analyses of Drug Trials: Reanalysis of Meta-Analyses,” BMJ 344, no. 7838 (2012): d7202; Lexchin (2012), supra note 1.

Lundh A. , “Industry Sponsorship and Research Outcome (Review),” Cochrane Database of Systematic Reviews no. 12 (2012).

Rennie D. , “When Evidence Isn't: Trials, Drug Companies and the FDA,” Journal of Law and Policy 15, no. 3 (2007): 991–1012; Prakash S. , “Did Merck Try to Censor Vioxx Critics?” National Public Radio, June 9, 2005; Prakash S. , “Conflicted Safety Panel Let Vioxx Study Continue,” National Public Radio, June 8, 2006; Goldacre B. , Bad Pharma: How Drug Companies Mislead Doctors and Harm (London: Faber & Faber, 2012).

See Rennie , supra note 50, at 1001.

See Zelenay , supra note 12.

Munos B. , “Lessons from 60 Years of Pharmaceutical Innovation,” Nature Reviews Drug Discovery 8, no. 12 (2009): 959–968.

Olson M. K. , “Are Novel Drugs More Risky for Patients Than Less Novel Drugs?” Journal of Health Economics 23, no. 6 (2004): 1135–1158.

Carpenter D. , “Corrosive Culture? The Dueling Forces of Autonomy and Industry Influence in FDA Pharmaceutical Regulation,” in Preventing Regulatory Capture: Social Influence and How to Limit It, Carpenter D. Moss D. , eds., (New York: Cambridge University Press, 2013): At Chap. 6; Hamburg M. , “Innovation, Regulation, and the FDA,” New England Journal of Medicine 363, no. 23 (2010): 2228–2232. For telling details, see Rodwin , supra note 43, and Rodwin M. , “Drug Advertising, Continuing Medical Education, and Physician Prescribing: An Historical Review and Reform Proposal,” Journal of Law, Medicine & Ethics 38, no. 4 (2010): 807–815.

Carpenter D. , “The Complication of Controlling Agency Time Discretion: FDA Review Deadlines and Postmarket Drug Safety,” American Journal of Political Science 56, no. 1 (2012): 98–114.

U.S. Office of the Inspector General, FDA's Review Process for New Drug Applications: A Management Review, 2003.

See Carpenter , supra note 56, at 99.

Wood A. Stein C. M. Woosley R. , “Making Medicines Safer - The Need for an Independent Drug Safety Board,” New England Journal of Medicine 339, no. 25 (1998): 1851–1854; see also Hilts , supra note 11; Moore T. , Deadly Medicine: Why Tens of Thousands of Heart Patients Died in America's Worst Drug Disaster (New York: Simon & Schuster, 1995).

See Zelenay , supra note 12.

On REMS, see Walker S. , “Maximizing REMS Potential,” Drug Topics 156, no. 9 (2012). On the Sentinel system, see Racoosin J. , “FDA's Sentinel Initiative: Active Surveillance to Identify Safety Signals,” in Strom B. L. Kimmel S. E. Hennessy S. , eds., Pharmacoepidemiology (New York: Wiley Online Library, 2012); Savage N. , “Digging for Drug Facts,” Communications of the ACM 55, no. 10 (2010). On AERS, see Weiss-Smith S. , “The FDA Drug Safety Surveillance Program: Adverse Event Reporting Trends,” Archives of Internal Medicine 171, no. 6 (2011): 591–593.

See 21 U.S.C. § 379h(b)(1)(A) (2013).

See Lexchin , supra note 29. The poorer safety record for priority drugs cannot be explained by the importance of the diseases they treat or the mechanisms by which they work.

Prescrire Editorial Staff, supra note 18.

Weissman R. , “From FDA, a Warning,” Boston Globe, March 16, 2013, at B5.

See Zelenay , supra note 12.

Angell M. , “Taking Back the FDA,” Boston Globe, February 26, 2007.

See Rennie , supra note 50, at 1006; Lemmens T. , “Pharmaceutical Knowledge Governance: A Human Rights Perspective,” Journal of Law, Medicine & Ethics 41, no. 1 (2013): 163–184.

Brody H. Light D. W. , “The Inverse Benefit Law: How Drug Marketing Undermines Patient Safety and Public Health,” American Journal of Public Health 101, no. 3 (2011): 399–404; Healy D. , Pharmageddon (Berkeley: University of California Press, 2012); see Goldacre , supra note 50.

Mintzes B. , “Pharmaceutical Sales Representatives and Patient Safety: A Comparative Prospective Study of Information Quality in Canada, France and the United States,” Journal of General Internal Medicine (forthcoming 2013); Prescrire Editorial Staff, “15 Years of Monitoring and One Simple Conclusion: Don't Expect Sales Representatives to Help Improve Healthcare Quality,” Prescrire International 15, no. 84 (2006): 154–159.

U.S. Government Accounting Office, “Prescription Drugs: FDA's Oversight of the Promotion of Drugs for Off-Label Uses,” Washington, D.C., 2008; Kiester M. , “DDMAC submissions,” FDA, available at <http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM246563.pdf> (last visited June 20, 2013).

Nguyen D. , “Changes in FDA Enforcement Activities Following Changes in Federal Administration: The Case of Regulatory Letters Released to Pharmaceutical Companies,” BMC Health Services Research 13 (2013): 27.

Krumholz S. Egilman D. , “Study of Neurontin: Ittrate to Effect, Profile of Safety (STEPS) Trial: A Narrative Account of a Gabapentin Seeding Trial,” Archives of Internal Medicine 171, no. 12 (2011): 1100–1107.

Eguale T. , “Drug, Patient, and Physician Characteristics Associated with Off-Label Prescribing in Primary Care,” Archives of Internal Medicine 172, no. 10 (2012): 781–788; Radley D. C. Finkelstein S. N. Stafford R. S. , “Off-Label Prescribing among Office-Based Physicians,” Archives of Internal Medicine 166, no. 9 (2006): 1021–1026.

For more detail, see Rodwin (2012), supra note 33, and Rodwin M. A. , “Rooting Out Institutional Corruption to Manage Inappropriate Off-Label Drug Use,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 654–664.

Waxman H. , “Prescription for Harm: The Decline in FDA Enforcement Activity,” in Special Investigations Division (Washington, D.C.: Committee on Government Reform, U.S. House of Representatives, 2006).

See Rennie , supra note 50; Rodwin , supra note 43.

Id. ( Rodwin ), at 130–159.

See Open Secrets, available at <http://www.opensecrets.org/lobby/indusclient.php?id=H04> (last visited June 20, 2013).

See Rodwin , supra note 43; Abraham , supra note 43; Abraham J. Davis C. , “Deficits, Expectations, and Paradigms in British and American Drug Safety Assessment,” Science Technology Human Values 32, no. 4 (2007): 399–431; Abraham J. , “Drug Evaluation and the Permisive Principle,” Social Studies of Science 39, no. 4 (2009): 569–598.

Warburton R. , “What Do We Gain from the Sixth Coronary Heart Disease Drug?” BMJ 327, no. 7426 (2003): 1237–1238.

Dukes M. Lunde I. , “The Regulatory Control of Non-Steroidal Anti-Inflammatory Agents,” European Journal of Clinical Pharmacology 19, no. 1 (1981): 3–10.

See Garattini Bertele , supra note 45.

Rodwin M. Abramson J. , “Clinical Trial Data as a Public Good,” JAMA 308, no. 9 (2012): 871–872; supra note 68; Duijnhaven R. , “Number of Patients Studied Prior to Approval to New Medicines: A Database Analysis,” PLoS Medicine 10, no. 3 (2013): e1001407.

See Republic, Lost, supra note 2, at Part IV.