Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-10T09:16:17.824Z Has data issue: false hasContentIssue false
  • English
  • Français

Rooting Out Institutional Corruption to Manage Inappropriate Off-Label Drug Use

Published online by Cambridge University Press:  01 January 2021

Marc A. Rodwin
Get access Rights & Permissions [Opens in a new window]

Extract

The Food and Drug Administration (FDA) authorizes the marketing of a drug only for uses that the manufacturer has demonstrated to be safe and effective, based on evidence from at least two clinical trials. However, the FDA does not regulate the practice of medicine, so physicians may prescribe drugs in any manner they choose. Prescribing drugs in ways that deviate from the uses specified in the FDA-approved drug label, package insert, and marketing authorization is referred to as off-label prescribing. This occurs when physicians prescribe a drug for a therapeutic purpose other than the one approved by the FDA; treat patients in a different age cohort or gender than the population on which it was tested; or prescribe a different dose, for a different duration of use, or a different mode of administration than indicated on the label.

Type
Symposium
Information
Journal of Law, Medicine & Ethics , Volume 41 , Issue 3 , Fall 2013 , pp. 654 - 664
Copyright
Copyright © American Society of Law, Medicine and Ethics 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

The FDA restricts marketing drugs off-label on two grounds. First, drugs marketed off-label are misbranded in violation of 21 U.S.C. § 331(a) (2000) and 21 U.S.C. § 352(a), (f) (2000), because the manufacturer provided false, misleading or inadequate information regarding its use. Second, off-label marketing constitutes introduction drugs for new unapproved uses in violation of 21 U.S.C. § 331(a) (2000), 21 U.S.C. §§ 331(d), 355(a) (2000) and 21 C.F.R. § 310.3(h)(4)-(5) (2000). See also, 21 C.F.R. § 310.303(a) (2000).Google Scholar
‘t Jong, G.W. Vulto, A. G. de Hoog, M. Schimmel, K. J. Tibboel, D. van den Anker, J. N., “Unapproved and Off-label Use of Drugs In A Children's Hospital,” New England Journal of Medicine 343, no. 15 (2000): 1125–1125.CrossRefGoogle Scholar
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. Eguale, T. Buckeridge, D. L. Winslade, N. E. et al., “Drug, Patient, and Physician Characteristics Associated with Off-Label Prescribing in Primary Care,” Archives of Internal Medicine 172, no. 10 (2012): 781–788.Google Scholar
Many patients are injured due to adverse medical events even when drugs are prescribed as approved by the FDA. See, Light, D. W. Lexchin, J. Darrow, J., “Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 590–600.CrossRefGoogle Scholar
The AMA holds that physicians have a right to use drugs off-label when such use is based on “sound scientific evidence and … medical opinion.” American Medical Association, H-120.988 Patient Access to Treatments Prescribed by Their Physicians, available at <http://www.ama-assn.org/resources/doc/Policy-Finder/policyfiles/HnE/H-120.988.HTM> (last visited June 26, 2013).+(last+visited+June+26,+2013).>Google Scholar
For discussion of proposals that regulate physicians off-label prescribing, see Kessler, D. A., “Regulating the Prescribing of Human Drugs for Non-Approved Uses under the Food, Drug, and Cosmetic Act,” Harvard Journal on Legislation 15, no. 4 (1977): 693–760. Shapiro, S. A., “Limiting Physician Freedom to Prescribe a Drug for Any Purpose: The Need for FDA Regulation,” Northwestern University Law Review 73, no. 5 (1978): 801–872.Google Scholar
Rodwin, M. A., “Conflicts of Interest, Institutional Corruption, and Pharma: An Agenda for Reform,” Journal of Law, Medicine & Ethics 40, no. 3 (2012): 511–522.CrossRefGoogle Scholar
Rayburn, W. F. Farmer, K. C., “Off-label Prescribing during Pregnancy,” Obstetrics and Gynecology Clinics of North America 24, no. 3 (1997): 471–478.CrossRefGoogle Scholar
Soo Hoo, G. W., “Off-label, On Target?” Chest: Official Publication of the American College of Chest Physicians 126, no. 4 (2004): 1022–1025.CrossRefGoogle Scholar
Steinbrook, R., “Testing Medications in Children,” New England Journal of Medicine 347, no. 18 (2002): 1462–1470.CrossRefGoogle Scholar
Hampton, T., “Experts Weigh In on Promotion, Prescription of Off-Label Drugs,” JAMA 297, no. 7 (2007): 683–684; see Radley, et al., supra note 3.CrossRefGoogle Scholar
See Hampton, , supra note 11.Google Scholar
Id.Google Scholar
Id.Google Scholar
See Radley, et al., supra note 3.Google Scholar
Rodwin, M. A., “Independent Clinical Trials to Test Drugs: The Neglected Reform,” Saint Louis University Journal of Health Law & Policy 6, no. 1 (2012): 113–165.Google Scholar
Sismondo, S., “Ghost Management: How Much of the Medical Literature Is Shaped Behind the Scenes by the Pharmaceutical Industry?” PLoS Medicine 4, no. 9 (2007): e286: 1429–1433; (Sismondo, S., “Ghosts in the Machine Publication Planning in the Medical Sciences,” Social Studies of Science 39, no. 2 (2009): 171–198. See, also Sismondo, S., “Key Opinion Leaders, the Corruption of Medical Knowledge, and the Sunshine Act,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 1–27.Google Scholar
See, Lundh, A. Sismondo, S. Lexchin, J. et al., “Industry Sponsorship and Research Outcome,” Cochrane Database of Systematic Review 12 (2012): 1–88.Google Scholar
A developed literature reveals that the published medical literature is biased in that it is an unrepresentative sample of clinical trials. Since drug firms fund most clinical trials, they typically do not seek to publish studies that do not yield favorable results. For discussions of publication bias, see, e.g. Dickersin, K., “The Existence of Publication Bias and Risk Factors for Its Occurrence,” JAMA 263, no. 10 (1990): 1385–1389; Dickersin, K. Min, Y., “Publication Bias: The Problem That Won't Go Away,” Annals of the New York Academy of Sciences 703, no. 1 (2006): 135–148; Davidson, R. A., “Source of Funding and Outcome of Clinical Trials,” Journal of General Internal Medicine 1, no. 3 (1986): 155–158.Google Scholar
See Radley, et al., supra note 3.Google Scholar
Id. These statistics probably underestimate number of off-label uses that lack substantial scientific support, because many published studies are biased in favor of the drug manufacturer. See, Brown, A., “Understanding Pharmaceutical Research Manipulation in the Context of Accounting Manipulation,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 611–619; Feldman, Y. Gauthier, R. Schuller, T., “Curbing Misconduct in the Pharmaceutical Industry: Insights from Behavioral Ethics and the Behavioral Approach to Law,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 620–628.CrossRefGoogle Scholar
Poole, S. G. Dooley, M. J., “Off-Label Prescribing in Oncology,” Supportive Care in Cancer 12, no. 5 (2004): 302–305; see Hampton, , supra note 11.CrossRefGoogle Scholar
Id.Google Scholar
United States General Accounting Office, Off-Label Drugs: Reimbursement Policies Constrain Physicians in Their Choice of Cancer Therapies, Report to the Chairman, Committee on Labor and Human Resources, U.S. Senate (1991).Google Scholar
American Society of Clinical Oncology, “Reimbursement for Cancer Treatment: Coverage of Off Label Drug Indications,” Journal of Clinical Oncology 24, no. 19 (2006): 3206–3208.CrossRefGoogle Scholar
O’Reilly, J. Dalal, A., “Off-Label or Out of Bounds: Prescriber and Marketer Liability for Unapproved Uses of FDA-Approved Drugs,” Annals of Health Law 12, no. 2 (2003): 295–324.Google Scholar
See t’Jong, , supra note 2. In an effort to increase pediatric drug labeling, the FDA passed the FDA Modernization Act in 1997, which provides incentives such as extended patent protection to pharmaceutical companies for performing pediatric trials, and including pediatric drug labels to address basic dosing and other safety information.Google Scholar
See O'Reilly, , supra note 26.Google Scholar
See O'Reilly, Dalal, , supra note 26.Google Scholar
See Radley, et al., supra note 3. Despite the lack of scientific support, practice guidelines often recommend the use of drugs. See, Cosgrove, L. Wheeler, E. E., “Drug Firms, the Codification of Diagnostic Categories, and Bias in Clinical Guidelines,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 644–653.Google Scholar
Alexopoulos, G. S. Streim, J. E. Carpenter, D. Docherty, J. P., “Expert Consensus Guidelines for Using Antipsychotic Agents in Older Patients,” Journal Clinical Psychiatry 65, no. 2 (2004): 100–102; Food and Drug Administration, “FDA Issues Public Health Advisory for Antipsychotic Drugs Used for Treatment of Behavioral Disorders in Elderly Patients,” 2005, available at <http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm053171.htm> (last visited June 30, 2013); Wang, P. S. Schneeweiss, S. Avorn, J. Fischer, M. A. Mogun, H. Solomon, D. H. Brookhart, M. A., “Risk of Death In Elderly Users of Conventional vs. Atypical Antipsychotic Medications,” New England Journal of Medicine 353, no. 22 (2005): 2335–2341.+(last+visited+June+30,+2013);+Wang,+P.+S.+Schneeweiss,+S.+Avorn,+J.+Fischer,+M.+A.+Mogun,+H.+Solomon,+D.+H.+Brookhart,+M.+A.,+“Risk+of+Death+In+Elderly+Users+of+Conventional+vs.+Atypical+Antipsychotic+Medications,”+New+England+Journal+of+Medicine+353,+no.+22+(2005):+2335–2341.>Google Scholar
Cohen, J. P. et al., “Off-Label Use Reimbursement,” Food & Drug Law Journal 64, no. 2 (2009): 391–404; Steinberg, E. P. Tunis, S. Shapiro, D., “Insurance Coverage for Experimental Technologies,” Health Affairs 14, no. 4 (1995): 143–158; Todd, A. E., “No Need for More Regulation: Payors and Their Role in Balancing the Cost and Safety Considerations of Off-Label Prescriptions,” American Journal of Law & Medicine 37, nos. 2 & 3 (2011): 422–443.Google Scholar
Gleeson, S., “Blue Cross and Blue Shield Association's Coverage Policies,” in Proceedings of the 1990 Drug Information Association Meeting, “Unlabeled Uses of Marketed Drugs,” Washington, D.C., October 22–23, 1990.Google Scholar
See, e.g., Laetz, T. Silberman, G., “Reimbursement Policies Constrain the Practice of Oncology,” JAMA 266, no. 21 (1991): 2996–2999.CrossRefGoogle Scholar
National Cancer Institute, State Laws Requiring Third-Party Reimbursement for Off-Label Uses of Prescription Drugs for the Treatment of Cancer, State Cancer Legislative Database Program, Bethesda, , MD. See also, Francis, L. P., “Legitimate Expectations, Unreasonable Beliefs, and Legally Mandated Coverage of Experimental Therapy,” Indiana Health Law Review 1, no. 1 (2004): 213–251.Google Scholar
See Radley, et al., supra note 3; see Micromedex, Thompson, available at <http://www.micromedex.com/products/drug-dex/index.html> (last visited April 16, 2013).+(last+visited+April+16,+2013).>Google Scholar
American Society of Health-System Pharmacists, American Hospital Formulary Service Drug Information, available at <http://www.ashp.org/ahfs> (last visited April 16, 2013).+(last+visited+April+16,+2013).>Google Scholar
Agency for Healthcare Research and Quality, Summary Guides.Google Scholar
The Medical Letter, available at <http://secure.medicalletter.org/> (last visited April 16, 2013).+(last+visited+April+16,+2013).>Google Scholar
See Radley, et al., supra note 3. Other firms that have performed this work also exit. CambridgeSoft, a U.K. firm, reports on off-label uses of, but it ended its operation as an independent company in 2011 when it was sold to PerkinElmer, a laboratory instrument company.Google Scholar
Parkinson Pipeline Project, available at <www.pdpipeline.org> (last visited April 16, 2013)+(last+visited+April+16,+2013)>Google Scholar
Gleeson, S., “Blue Cross and Blue Shield Association's Coverage Policies,” Proceedings of the 1990 Drug Information Association Meeting, “Unlabeled Uses of Marketed Drugs,” Washington, D.C., October 22–23, 1990. See also, Cohen, et al., supra note 32.Google Scholar
See, 42 C.F.R. § 414.930 (2010).Google Scholar
Abernethy, A. P. Raman, G. Balk, E. M. Hammond, J. M. Orlando, L. A., “Reliability of Compendia Methods for Off-Label Oncology Indications,” Annals of Internal Medicine 150, no. 5 (2009): 336–343; Tillman, K. Burton, B. Jacques, L. B. Phurrough, S. E., “Compendia and Anticancer Therapy Under Medicare,” Annals of Internal Medicine 150, no. 5 (2009): 348. See also, Tunis, S. R. Pearson, S. D., “Coverage Options for Promising Technologies: Medicare's ‘Coverage with Evidence Development,’” Health Affairs 25, no. 5 (2006): 1218–1230; Foote, S. B. Town, R. J., “Implementing Evidence-Based Medicine through Medicare Coverage Decisions,” Health Affairs 26, no. 6 (2007): 1634–1642.CrossRefGoogle Scholar
See Cohen, et al., supra note 32.Google Scholar
Craft, G. S. Jr., “Promoting Off-Label in Pursuit of Profit: An Examination of Fraudulent Business Model,” Houston Journal of Health Law & Policy 8, no. 1 (2007): 103–131; Fugh-Berman, A. Melnick, D., “Off-Label Promotion, On-Target Sales,” PLoS Medicine 5, no. 10 (2008): e210.Google Scholar
Kesselheim, A. S. Studdert, D. M. Mello, M. M., “Whistle-Blowers' Experiences in Fraud Litigation against Pharmaceutical Companies,” New England Journal of Medicine 362, no. 19 (2010): 1832–1839; Mello, M. M. Studdert, D. M. Brennan, T. A., “Shifting Terrain in the Regulation of Off-Label Promotion of Pharmaceuticals,” New England Journal of Medicine 360, no. 15 (2009): 1557–1566.CrossRefGoogle Scholar
Government Accountability Office (GAO), Prescription Drugs: FDA's Oversight of the Promotion of Drugs for Off-Label Uses, Washington, D.C., July 2008, available at <http://www.gao.gov/products/GAO-08-835> (last visited June 30, 2013).+(last+visited+June+30,+2013).>Google Scholar
42 U.S.C. § 1320a-7b (1990).Google Scholar
31 U.S.C. § 3729 (2000).Google Scholar
Stoffelmayr, J. K., “Comment: Products Liability and Off-Label Uses of Prescription Drugs,” University of Chicago Law Review 63, no. 1 (1996): 275–304. See O'Reilly, Dalal, , supra note 26.CrossRefGoogle Scholar
Kesselheim, A. S. Mello, M. M. Studdert, D. M., “Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints,” PLoS Medicine 8, no. 4 (2011): E1000431: 1–9.CrossRefGoogle Scholar
For analysis of the how drug firms market their products to sell drugs both for prescribed and off label uses, see the following in Journal of Law, Medicine & Ethics, 41, no. 3 (2013): Sismondo, S., “Key Opinion Leaders and the Corruption of Medical Knowledge: What the Sunshine Act Will and Won't Cast Light On,” at 635–643; Sah, S. Fugh-Berman, A., “Physicians under the Influence: Social Psychology and Industry Marketing Strategies,” at 665–672; and Landa, A. S. Elliott, C., “From Community to Commodity: The Ethics of Pharma-Funded Networking Sites for Physicians,” at 673–679.Google Scholar
The other violations included: Overcharging government health programs, monopoly/ antitrust, the Medicare and Medicaid Anti-Kickback act, concealing stud findings, poor manufacturing practices, financial violations, illegal distribution, and environmental violations.Google Scholar
Almashat, S. Preston, C. Waterman, T. Wolfe, S., “Rapidly Increasing Criminal and Civil Monetary Penalties against the Pharmaceutical Industry: 1991 to 2010,” Public Citizen's Health Research Group (2010).Google Scholar
GlaxoSmithKline, $3 billion (11/11); Merck, Sharp & Dohme $950 million (11/11); Johnson & Johnson, $158 million (4/11); Scios (Subsidiary of Johnson & Johnson) $85 million (10/11); Elan Corporation, PLC $60 million (2/11); UCB, Inc, $34.4 million (6/11); and Novo Nordisk, Inc. $25 million (6/11).Google Scholar
Evans, D., “When Drug Makers' Profits Outweigh Penalties,” Washington Post, March 21, 2010, available at <http://www.washingtonpost.com/wp-dyn/content/article/2010/03/19/AR2010031905578.html> (last visited April 16, 2013). (last visited April 16, 2013).' href=https://scholar.google.com/scholar?q=Evans,+D.,+“When+Drug+Makers'+Profits+Outweigh+Penalties,”+Washington+Post,+March+21,+2010,+available+at++(last+visited+April+16,+2013).>Google Scholar
Id. The $2.75 billion Pfizer has paid in off-label penalties from 2004 to 20010 is slightly more than 1 percent of its revenue of $245 billion from 2004 to 2008.Google Scholar
Steinman, M. A. Bero, L. A. Chen, M. Landefeld, C. S., “Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents,” Annals of Internal Medicine 145, no. 4 (2006): 284–293 for the data on off-label sales, see Radley, et al., supra note 3.CrossRefGoogle Scholar
Kesselheim, A. S. et al., “False Claims Act Prosecution Did Not Deter Off-Label Drug Use in the Case of Neurontin,” Health Affairs 30, no. 12 (2011): 2318–2327; see also Sentencing Memorandum of the United States, United States v. Warner-Lambert Co. LLC, Criminal No. 04–10150 RGS (Mass, D., filed June 2, 2004).CrossRefGoogle Scholar
Blumberg, E., “The Park Doctrine,” speech given to the Food and Drug Law Institute, October 13, 2010.Google Scholar
See, also. O'Leary, P., “Credible Deterrence: The Park Doctrine and the FDA in the 21st Century,” Food and Drug Law Journal 68, no. 2 (forthcoming 2013); Boozang, K., “Responsible Corporate Officer Doctrine: When Is Falling Down on the Job a Crime?” St. Louis University Journal of Health Law & Policy 6, no. 1 (2012): 77–112.Google Scholar
The doctrine of commercial free speech arose in the 1970s in a series of cases involving restrictions on advertising by lawyers and physicians. In Virginia State Bd. of Pharmacy v. Citizens Consumer Council, 425 U.S. 748 (1976), the court struck down a law that prevented pharmacies from advertising the prices of prescription drugs. In Central Hudson Gas & Electric Corp. v. Public Service Commission, 447 U.S. 557 (1980), the court set forth a framework to determine whether the governmental interest outweighs the interest in commercial free speech. The implications for pharmaceutical marketing arose in Washington Legal Foundation v. Friedman, 13 F. Supp. 2d 51 (Dist. Ct. D.C. 1998) and Washington Legal Foundation v. Henney, 128 F. Supp. 2d 11 (Dist. Ct. D.C. 2000).Google Scholar
Washington Legal Foundation v. Friedman, 13 F. Supp. 2d 51 (Dist. Ct. D.C. 1998); Washington Legal Foundation v. Henney, 128 F. Supp. 2d 11 (Dist. Ct. D.C. 2000). The lawsuits challenged the Food and Drug Administration, Guidance for Industry on 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, January 2009, available at <http://www.fda.gov/oc/op/goodreprint.html> (last visited April 16, 2013); see also, Gilhooley, M., “Drug Safety and Commercial Speech: Television Advertisements and Reprints on Off-Label Uses,” San Diego Law Review 47, no. 3 (2010): 845–897.Google Scholar
Kesselheim, A. S., “Off-Label Drug Use and Promotion: Balancing Public Health Goals and Commercial Speech,” American Journal of Law & Medicine 37, no. 1 (2011): 225–257; Danzis, S. D., “Off-label Communications and Prescription Drugs,” in Ethics and the Pharmaceutical Industry, Gorrie, T. M. Santoro, M. A., eds. (Cambridge: Cambridge University Press, 2005): 184–195. The FDA's most recent policy on distribution of reprints is from 2009. U.S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner, Office of Policy, Guidance for Industry: 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, January 2009, available at <http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0053-gdl.pdf> (last visited April 16, 2013))Google Scholar
A recent second circuit judicial decision, interprets the first amendment to protect the speech of drug detailers and, if the decision is followed by other courts of appeal, will make it harder to prosecute off label promotion. United States v. Caronia, 703 F.3d 149 (2d Cir. 2012).Google Scholar
See Hampton, , supra note 10. See, also, Rose, S. L., “Patient Advocacy Organizations: Institutional Conflicts of Interest Policies, Trust, and Trustworthiness,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 680–687.Google Scholar
For discussion of proposals to regulate off-label prescribing, see Rosoff, P. M. Coleman, D. L., “Case for Legal Regulation of Physicians' Off-Label Prescribing,” Notre Dame Law Review 86, no. 2 (2011): 649–692; Dresser, R. Frader, J., “Off Label Prescribing: A Call for Heightened Professional and Government Oversight,” Journal of Law, Medicine & Ethics 37, no. 3 (2009): 476–486; Randall, R. S., “Regulating Off-label Drug Use – Rethinking the Role of the FDA,” New England Journal of Medicine 358, no. 14 (2008): 1427–1429.Google Scholar
Richard Epstein suggests that voluntary non-governmental organizations should regulate on-label and off-label drug use. Epstein, R., “Against Permititis: Why Voluntary Organizations Should Regulate the Use of Cancer Drugs,” Minnesota Law Review 94, no. 1 (2009): 1–30; see also, Todd, A. E., “No Need for More Regulation: Payors and Their Role in Balancing the Cost and Safety Considerations of Off-Label Prescriptions,” American Journal of Law & Medicine 37, nos. 2 & 3 (2011): 422–443.Google Scholar
Hall, R. F. Sobotka, E. S., “Inconsistent Government Policies: Why FDA Off-label Regulation Cannot Survive First Amendment Review under Greater New Orleans,” Food Drug Law Journal 62, no. 1 (2007): 1–48; Christopher, W. L., “Off-Label Drug Prescription: Filling the Regulatory Vacuum,” Food Drug Law Journal 48, no. 2 (1993): 181–228; Psaty, B. M. Ray, W., “FDA Guidance on Off-Label Promotion and the State of the Literature from Sponsors,” JAMA 299, no. 16 (2008): 1949–1951.Google Scholar
The FDA has a long-standing policy of not interfering with the practice of medicine. However, the FDA has declared that “where the unapproved use of an approved new drug becomes widespread or endangers the public health, the FDA will investigate and take whatever action is warranted to protect the public.” See, “Legal status of Approved Labeling for Prescription Drugs; Prescribing for Uses Unapproved by the Food and Drug Administration,” Federal Register 37 (August 15, 1972): 16503–16505, at16504.Google Scholar
Dr.Safford, Randall has suggested that the FDA track study label drug use but without a system that would systematically track prescribing. See, Stafford, R. S., “Regulating Off-Label Drug Use – Rethinking the Role of the FDA,” New England Journal of Medicine 358, no. 14 (2008): 1427–1429.CrossRefGoogle Scholar
Eguale, Tewodros and colleagues tracked off label drug use in Canada using information from electronic medical records. The record system prompted physicians to enter information on treatment indication for each drug prescribed, drawing on a menu of approved and on label indications and also allowed physicians to enter options not listed. See Eguale, et al., supra note 3.Google Scholar
This information does not pose a significant risk for patient privacy. Pharmacies that sell prescription data anonymize the data so that it does not reveal the patient's name.Google Scholar
Typically, the best way to test drug is through randomized, controlled clinical trials. However, it is not always possible to conduct such trials and often those trials may not be conducted on certain population groups.Google Scholar
Behrman, R. E. Benner, J. S. Brown, J. S. McClellan, M. Woodcock, J. Platt, R., “Developing the Sentinel System – A National Resource for Evidence Development,” New England Journal of Medicine 364, no. 6 (2011): 498–499.Google Scholar
It is also reasonable to obtain pertinent marketing data from manufacturers in order to track off-label use. Drug firms routinely obtain data that reveals which physicians prescribe their drugs, the doses prescribed, and the duration of the prescription. Firms sometimes also obtain data that reveals the patient's medical condition, which can help indicate the purpose for which the drug was prescribed. Legislation could require that drug firms share their marketing data with the FDA and public health officials.Google Scholar
For a discussion of tax policy, value-based pricing and other ways to change the economic incentives of drug firms, see Gagnon, M.-A., “Corruption of Pharmaceutical Markets: Addressing the Misalignment between Financial Incentives and Public Health,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 571–580. For proposals that change economic incentives by separating drug development from drug marketing, see Sismondo, S., “Key Opinion Leaders and the Corruption of Medical Knowledge: What the Sunshine Act Will and Won't Cast Light On,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 635–643.CrossRefGoogle Scholar
Some states allow physicians to dispense drugs. The income that dispensing physicians earn is a function of the difference between their reimbursement and the cost of purchasing the drug, as well as administration of their dispensary. Like pharmaceutical firms, dispensing physicians have an incentive to prescribe off-label when it is profitable. We should therefore also end dispensing physicians' economic incentive to prescribe off-label. Similar rules should regulate drug-dispensing institutions, which are closely affiliated with physicians (such as freestanding pharmacies in which physicians invest), so that physicians do not have an incentive to prescribe medications off-label.Google Scholar
For background on the Medicare hospital cost reporting system see Kane, N. M. Magnus, S. A., “The Medicare Cost Report and the Limits of Hospital Accountability: Improving Financial Accounting Data,” Journal of Health Politics, Policy and Law 26, no. 1 (2001): 81–106; Magnus, S. A. Smith, D. G., “Better Medicare Cost Report Data Are Needed to Help Hospitals Benchmark Costs and Performance,” Health Care Management Review 25, no. 4 (2000): 65–76. Medicare provides information on its cost reports online at <http://www.cms.gov/Research-Statistics-Data-and-Systems/Files-for-Order/CostReports/index.html> (last visited March 21, 2013).CrossRefGoogle Scholar
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): 29–33.CrossRefGoogle Scholar
Steinbrook, R., “For Sale: Physicians' Prescribing Data,” New England Journal of Medicine 354, no. 26 (2006): 2745–2747; Greene, J. A., “Pharmaceutical Marketing Research and the Prescribing Physician,” Annals of Internal Medicine 146, no. 10 (2007): 742–749.CrossRefGoogle Scholar
21 C.FR. §310.303, §314.80, §314.98, §317.70 (c)(6)(iii) (A).Google Scholar
See Rodwin, , supra note 16 and Rodwin, M. A., “Five Un-Easy Pieces to Pharmaceutical Policy Reform,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 581–589. In a similar vein, several scholars have called for the creation of an independent government entity to compare the safety and effectiveness of competing drugs. See Light, D. W. Lexchin, J. Darrow, J., “Institutional Corruption of Pharmaceuticals and the Consequences for Patients,” Journal of Law, Medicine & Ethics 41, no. 3 (2013): 590–600.CrossRefGoogle Scholar
Rodwin, M. A., “Drug Advertising, Continuing Medical Education, and Physician Prescribing: A Historical Review and Reform Proposal,” Journal of Law, Medicine & Ethics 38, no. 4 (2010): 807–815.CrossRefGoogle Scholar